Issues Chapter OutlineHow do we know what we know?How do scientists make discoveries and advance our knowledge?What constitutes a ‘discovery’ in science?How is science creative?Does science contain absolute truths?How do ethics and morals fit into science?How do scientists make ethical decisions in a social context?How are decisions made on social issues, and to what extent can science help in these decisions?What rights do animals have? How do we safeguard those rights?How do we safeguard the rights of experimental subjects?Properties of living organisms (organization, metabolism, selective response, homeostasis,growth and biosynthesis, genetic material, reproduction, population)Hypotheses and theoriesExperimental science versus naturalistic scienceNormal science and paradigm shiftsScience and societyBiological ethicsScience Develops Theories by Testing HypothesesHypothesesHypothesis testing in science TheoriesA theory describing the properties of living systemsScientists Work in Paradigms, Which Can Help Define Scientific RevolutionsParadigms and scientific revolutions Molecular genetics as a paradigm in biology The scientific communityScientists Often Consider Ethical IssuesEthicsResolving moral conflicts Deontological and utilitarian ethics Ethical decision-makingEthical Questions Arise in Decisions About the Use of Experimental SubjectsUses of animalsThe animal rights movementHumans as experimental subjects1Biology: Science and EthicsBiology is the scientific study of living systems. Our gardens, our pets, our trees, and our fellow humans are all examples of living systems.We can look at them, admire them, write poems about them, and enjoy their company. The Nuer, a pastoral people of Africa, care for their cattle and attach great emotional value to each of them. They write poetry about—and occasionally to—their cattle, they name themselves after their favorite cows or bulls, and they move from place to place according to the needs of their cattle for new pastures. They come to know individual cattle very well, almost as members of the family. The Nuer have also acquired a vast store of useful knowledge about the many animal and plant species in their region. Many other people who live close to the land have a similar familiarity with their environment and the many species living in it.Scientific understanding of the world around us grew out of this kind of familiarity with nature, supplemented by a tradition of systematic testing. In this chapter we examine the methods of science in general and the application of those methods to the study of living systems.Because living systems are complex and continually changing, an understanding of these systems often requires special methods of investigation or ways of formulating thoughts. This chapter describes the special methods that have come to be called science. Many people think that science is defined by its subject matter, but this is not correct. Science is defined by its methods.The scientific method does not answer questions about values and, therefore, cannot by itself answer questions such as whether certain types of research should be done, or to what uses scientific results should be put. Such decisions often involve a branch of philosophy called ethics. Many issues confronting societies today have a scientific dimension. Policy decisions on such issues involve both science and ethics.Science Develops Theories by Testing HypothesesThe essence of science is the formulation and testing of certain kinds of statements called hypotheses. At the moment of its inception, a hypothesis is a tentative explanation of events or of how something works. What makes science distinctive is that hypotheses are subjected to rigorous testing. Many hypotheses are falsified (rejected as false) by such testing. Eliminating one hypothesis often helps us to frame the next hypothesis. If a hypothesis is repeatedly tested and not falsified, it may be put together with related hypotheses that have also withstood repeated testing. Such a group of related hypotheses may become recognized as a theory.HypothesesHypotheses must be statements about the observable universe, formulated in such a way that they can be tested. Observations of the material2 world that we make with our senses (aided in some cases by scientific instruments) are called empirical observations. To be a hypothesis, a statement must be capable of being tested by comparison with such empirical observations. Observations gathered for testing hypotheses are called data. Karl Popper, a philosopher of science, said that scientific hypotheses must always be tested in such a way that they can be rejected if they turn out to be inconsistent with observations—in his words, they must always be falsifiable.Certain types of statements cannot be used as scientific hypotheses because they are not subject to testing and falsification. This includes esthetic judgments about what is valuable, beautiful, or likable, e.g., “I like my kind of music, whatever you may say about it.” Moral judgments and religious concepts are also not scientific hypotheses because observational data are not sufficient to test their truth. This means that a devout person’s belief in God cannot be shaken by any demonstration of an empirical fact or observation. To a devout believer, no such demonstration is even possible. The same is true of strongly held beliefs about the goodness of human equality or the wrongfulness of inflicting death.Hypotheses, therefore, must be: (1) testable and (2) falsifiable. A third characteristic is that of simplicity—a problem should be stated in its basic and simplest terms. When several hypotheses fit the facts of a problem, scientists usually choose the simplest hypothesis. An example is the appearance of crop circles: the simplest hypothesis—that human activity created the patterns—is more likely than the more complex hypothesis— alien activity—because in the latter case we would also need to explain who the aliens are, where they came from, how they came, and so on.Specific versus general hypotheses. Hypotheses that are easy to verify generally tell us very little. For example, the hypothesis “this frog will jump if I touch it” can be tested by touching the frog and observing what happens. If the frog does jump, then our hypothesis is verified or confirmed; if the frog does not jump, then our hypothesis is falsified or disconfirmed. However, the confirmation of this hypothesis about a particular frog is far from an important scientific discovery. It is relatively unimportant because it is too specific, which is exactly what makes it verifiable. Suppose, now, that we examine the much bolder hypothesis “all animals will react when stimulated.” We can test this second hypothesis in the same way that we tested the first, by touching or otherwise stimulating some animals, and we could also declare that the hypothesis would be falsified if one animal failed to respond. (Even then, we could never be sure, for it might respond in a way that we do not immediately notice, e.g., by remembering the event and responding at a later time.) But what if the animals tested do all respond? Does this verify that all animals will respond? Suppose we test 5 animals in a row, or 5000? No finite number of successes would be sufficient to verify the hypothesis for all animals and all circumstances. This is the kind of hypothesis that science usually examines: hypotheses that could potentially be falsified each time that wetest them, but cannot be absolutely verified for all possible occurrences.Falsified hypotheses are rejected, and new hypotheses (which may in some cases be modifications of the original hypotheses) are suggested in their place. To extend the previous example, the hypothesis, “all frogs will jump if touched” would be falsified if 2 out of 2000 frogs did not jump.We could, however, modify the original hypothesis to one that is consistent with our data, e.g., “frogs will usually jump if touched.” In practice, we might also want to be specific about the nature of the stimulus (how sharp the object, how firm the touch), the response (how frequent, how strong), and other particulars (the species or size of frog used, the temperature, and so on).If testing a hypothesis does not reject it, we may want to generalize the hypothesis. For example, if a hypothesis tested using rats has not been falsified, we might want to apply the hypothesis to people as well, or to all animals. However, we can never know how far we can extrapolate (generalize) results unless we continue to try to falsify our premise under different conditions. In this way, the testing of hypotheses allows us to draw conclusions about the observable world, but only to the extent that we have tested many possible circumstances and conditions.Ways of devising hypotheses. One form of reasoning is called deduction, defined as reasoning that guarantees the truth of a conclusion if we accept the truth of the premises. Deduction is frequently used to set up testable hypotheses: “If organisms of type X require oxygen to live, then this individual of type X will die if I put it in an atmosphere without oxygen.” If the organism lives, then one of the premises must be rejected: either organisms of type X do not always require oxygen, or else this individual was not of type X. Another type of reasoning, called induction, may be defined as reasoning that does not guarantee the truth of any conclusions drawn, except in terms of probabilities. Science often uses induction to generalize from specific hypotheses, such as when we reason from five frogs to all frogs or from frogs and rats to all animals. Induction is also commonly used in everyday life: “I have liked pizza in each of the restaurants where I have ever eaten it; therefore I will like pizza in any other restaurant.” Induction allows us to reason beyond what we know with certainty, but in statistical terms only: I have always liked pizza, and I will probably like the next one that I try. However, because induction never guarantees the truth of any result, generalizations made by induction always need to be tested further. If I actually tried pizza in 450 restaurants that I had never tried before, I might discover that I only like the pizza in 442 of them, and that there are 8 places that serve pizza that I don’t like. The probability that I will like the pizza in a randomly chosen restaurant is thus 442 out of 450, or about 98.2%.One common way of reasoning in science is to start with data already gathered, use induction to generalize and to formulate a hypothesis, use deduction to set up a test situation, and test the hypothesis through further observation. In our example, I can start with the five frogs that respond to touch, create the hypothesis that “all animals will respond to touch,” reason by deduction that, if all animals will respond to touch, then this rat and that starfish will respond, and finally set up an experiment to test the hypothesis and see if it works as expected. This process is often called the scientific method. In reality, few scientists adhere rigidly to this prescription.Deduction and induction are only two of the many ways in which scientists go about the business of formulating hypotheses. Other ways include (1) intuition or imagination, (2) esthetic preferences, (3) religious and philosophical ideas, (4) comparison and analogy with otherprocesses, and (5) serendipity, or the discovery of one thing while looking for something else. Moreover, these ways may be mixed or combined. For example, Albert Einstein declared that he arrived at his hypotheses about the physics of the universe by considering esthetic qualities such as beauty or simplicity and by asking, “if I were God, how would I have made the world?”. Einstein also said that “imagination is more important than knowledge,” a remark that is particularly true for the formulation of hypotheses (Figure 1.1). Nobel Prize-winning physicist Niels Bohr said that his hypothesis of atomic structure (the heavy nucleus in the center, with the electrons circling rapidly around it, “like a miniature solar system”) first occurred to him by analogy with our solar system. Alexander Fleming found the first antibiotic as the result of a laboratory accident: on dishes of bacteria that should have been thrown away earlier, he observed clear areas where fungi had overgrown the bacteria. His hypothesis, that a product of the fungi had killed the bacteria, was validated by tests, and that fungal product is what we now know as penicillin. As these several examples show, hypotheses are formed by all kinds of logical and extralogical processes, which is one more reason why they must be subjected to rigorous testing afterward.Biology: hypothesis testing in living systems. Animals, plants, and bacteria are complex and variable. So are other living systems, large and small, from ecosystems to individual cells. No individual animal or plant is exactly like any other animal or plant. At any moment, living systems that are otherwise similar may differ in external conditions,Figure 1.1Imaginative hypotheses may originate from various logical or extralogical processes, especially from young scientists. Does the idea shown here qualify as a scientific hypothesis? Why, or why not? Is it testable? internal conditions, or in the way in which these conditions interact. Further, the same individual is not exactly the same from one day to the next. Because living systems vary, tests must be repeated. If the hypothesis is tested in one animal, or one cell, and a particular response occurs, the result is far less reliable as a means of prediction than if 10 animals, or 100 cells, all responded in the same way. What often happens, however, is that 9 out of 10 animals, or 94 of 100 cells, respond in one way and the remainder in another way. Interpretation of the results from tests on variable systems usually requires statistical treatment to ascertain whether the observed differences are ‘real’ or can be explained by random variation. The differing responses may come from a source of variation that has not yet been identified, and scientists who study the anomalous cases sometimes discover new, previously overlooked phenomena.A definition of science. Science may now be defined as a method of investigation based on the testing of hypotheses by organized comparisons with empirical evidence. Notice that this makes scientific statements tentative, or provisional, and subject to possible falsification and rejection. Repeated exposure of our hypotheses to possible refutation increases our confidence in these hypotheses when test results agree with predictions, but no amount of testing can guarantee absolute truth.Any hypothesis that is tested again and again, always successfully, is considered well supported and comes to be generally accepted. It may be used as the basis for formulating further hypotheses, so there is soon a cluster of related hypotheses, supported by the results of many tests, which is then called a theory. (Some people say that a widely accepted theory becomes a ‘law,’ but most philosophers of science do not recognize a ‘law’ as anything but a useful generalization.)Hypothesis testing in scienceScientists test hypotheses by comparing them with the real world through empirical observations. Scientists differ from one another, however, in the ways in which hypotheses are tested. Some scientists do all their work in laboratories with specially designed equipment; other scientists gather data and specimens in the field for analysis and interpretation (Figure 1.2).Some scientists test hypotheses by conducting experiments—artificially contrived situations set up for the express purpose of testing some hypothesis. Most experimental sciences seek to answer questions of the form “How does X work?”. The scientist designs an experiment such that, if the hypothesis is true, a certain outcome is expected (or not expected). Then, the results of the experiment are determined ‘objectively,’ which means, in this context, without bias either for or against the hypothesis being tested.In many experiments an experimental situation or group is compared with a control situation or with a control group. Ideally, the control group exactly matches the experimental group in all variables except the one being tested. For example, animals given a new drug are compared with animals in a similar group—the control group—that are not given the drug. The control group is given a substance similar to whatever is given to the experimental group, but lacking the one ingredient being tested. The two groups are selected and handled so as to be equivalent in every other way: similar animals, similar cages, similar temperatures, similar diets, and so on.As an example of the experimental approach, consider the following experiment in bacterial genetics that was conducted by Joshua and Esther Lederberg. (This experiment was part of the basis for Joshua’s subsequent Nobel Prize.) Most bacteria are killed by streptomycin, but the Lederbergs exposed the common intestinal bacterium Escherichia coli to this drug and were able to isolate a number of streptomycin-resistant bacteria. They allowed these bacteria to reproduce and were able to show that resistance to streptomycin was inherited by their offspring. In other words, the change to streptomycin resistance was a permanent genetic change; such changes are called mutations (see Chapter 3, pp. 67–69). The discovery of resistance gave the Lederbergs two hypotheses to test. The first (the induced-mutation hypothesis) was that the mutation had been induced, or caused, by exposure to the streptomycin. The second (the prior-mutation hypothesis) was that the bacteria had mutated before exposure to the streptomycin, in which case the mutation would be independent of the exposure. To dis-tinguish between these hypothe-ses, the Lederbergs devised the experiment shown in Figure 1.3. In this experiment, a copy, or replica, of the original plate of bacteria was made. Only the replica, not the original, was exposed to streptomycin, and the position of each bacterial colony was noted. The induced-mutation hypothesis predicted that bacteria exposed to streptomycin would mutate, but that unexposed bacteria would not. In fact, most of the bacteria died, but a few survived and were thus identified as being streptomycin resistant. To test the prior-mutation hypothesis, the Lederbergs went back and tested the colonies from the original plate. They discovered that the same colonies that were streptomycin resistant on the replica plate were also streptomycin resistant on the original plate. These findings support the priormutation hypothesis for this particular sample of bacteria.The prior-mutation hypothesis for drug resistance had been tested and not falsified in the case of one mutation in one species ofTransferring and examining solutions in a biochemistry laboratory.Examining cells with an electron microscope.Figure 1.3The replica-plating experiment of Lederberg and Lederberg.bacteria. How far could the finding be generalized? From this one experiment alone, one cannot tell. However, other investigators repeated the experiment for other mutations and other species of microorganisms. So far, the hypothesis of prior mutation has not been falsified. It is difficult to test the hypothesis in large or long-lived organisms, but most scientistsA wooden post slightly smaller than the culture plate is covered with sterile velvet. A bacterial plate without streptomycin is pressed onto the velvet, so that bacteria from the original plate rub off onto the velvet.original plate without streptomycinA new plate containing streptomycin is pressed onto the velvet.Bacteria are picked up from the velvet, and their locations on the new plate match the colony locations on the original plate. The new plate is thus a replica of the original.replica plate containing streptomycinThe replica plate is covered and incubated under conditions that stimulate bacterial growth. Only an occasional colony grows.Because the plate contained streptomycin, any colony that grows must be composed of streptomycin-resistant bacteria.same locationincubation original plate without streptomycinThe original plate has never been exposed to streptomycin.Bacterial samples from several locations on this plate are now taken and tested.The sample from the location where a streptomycin-resistant colony grew on the replica plate grows in a test tube with streptomycin, showing that some bacteria in this location on the original plate were streptomycin resistant before they were exposed to the streptomycin in the experiment.Samples from other locations do not grow in test tubes containing streptomycin, showing that other colonies on the original plate are not streptomycin resistant.The result falsifies the hypothesis of induced mutations, but is consistent with the hypothesis that the bacteria mutated before they were exposed to streptomycin. are willing to assume the truth of the hypothesis for all organisms. There are many species (and thousands of mutations for each species) that have never been tested in this way, which leaves opportunities for the hypothesis to be falsified in the future.An introduction to naturalistic science. Another type of hypothesis testing is one in which direct experimental manipulation is either impossible or undesirable. For example, if an animal behaviorist wishes to study mating behavior under natural conditions, then any experimental manipulation that alters these natural conditions must be avoided. Thus we see ornithologists hiding in blinds to study birds, while other naturalists photograph their subjects by using telephoto lenses. The extinct species studied by paleontologists cannot be recreated in the laboratory to permit an experiment. We can refer to these sciences as naturalistic sciences because their method is based primarily on naturalistic observation rather than experiment. Naturalists do test hypotheses, but they do so by patient observation and record keeping. Naturalists often use control groups by comparing observations made when certain conditions are present with similar observations made when one of the conditions is not. The major difference between the experimental and the naturalistic sciences is that experimentalists set up and control their experiments, while naturalists can only observe and record those ‘experiments’ that occur in nature. This often means that naturalists must search the world over for the right circumstances, or must wait patiently for the right circumstances to occur.The naturalistic sciences, moreover, are historical sciences. Any scientist seeking to understand why mammals differ from reptiles, or why the U.S. economy differs from the Japanese economy, will soon realize that the histories of animals, or of economies, form an important part of the explanation.There are many types of questions in the naturalistic or historical sciences. The most characteristic type of question in these sciences is, “How did X get to be that way?”. For example, a scientific team led by Rebecca Cann examined the DNA inside the mitochondria (the major energyproducing cell parts) of a large number of human populations. Mitochondrial DNA is always inherited from the mother, never from the father. Cann and her co-workers found that the chemical structure of the mitochondrial DNA in certain populations was very similar to its structure in other populations, allowing groups of related populations to be recognized. These scientists hypothesized that populations with similar mitochondrial DNA sequences share a close common descent through female lineages. This hypothesis explains the patterns of similarity among mitochondrial DNA sequences by a series of progressively ‘smaller’ hypotheses about the past histories of a given set of populations: that the populations of the Americas all share a common descent, that the populations of New Guinea all share a common descent, and so on. Some of these smaller hypotheses are falsified by the data, and must be replaced by modified hypotheses: New Guinea, for example, forms two clusters, and we can set up the hypothesis that it was colonized twice, with each line of descent forming a separate cluster. As modified in this manner, these smaller hypotheses of geographic dispersal are now interpreted as part of a common pattern of descent (see Figure 7.7, p. 224), with an area of origin in Africa. The data are consistent with a hypothesis that all human populations are descended from an ancestral African population, or from a single ancestral female, nicknamed ‘Eve’ in the popular press. Like most other explanations in the natural sciences, the ‘Eve hypothesis’ explains present conditions on the basis of their past history, an evolutionary or historical mode of explanation.TheoriesA theory is a coherent set of related and well-tested hypotheses that explain a broad set of observations and that guide scientific research. Theories are usually developed by the testing of hypotheses, aided in many cases by mathematical and logical analysis of the resulting data. Theories then inspire future hypotheses and future tests. Most theories contain explanatory language that helps us understand some observed phenomena. One of the most important features of a good theory is that it may suggest new and different hypotheses. A theory of this kind is a stimulus to further research and is sometimes called a productive theory. A theory may be productive for a while and then no longer stimulate new research. The theories that last are the ones that remain productive the longest, while the less productive ones are often abandoned. Sometimes they are abandoned without ever being fully disproved. In other cases, it is the falsification of one of its hypotheses (or the failure of a crucial test) that causes a theory to be rejected. Remember that the hypotheses that make up a theory are always subject to possible refutation. Even a longcherished theory may be abandoned (or greatly modified) if it no longer holds predictive or explanatory power.Theoretical language and models. A theory usually contains language that helps communicate its subject matter. Many theories also use a simplified mathematical or visual form, called a model. Such a model, while not a formal part of the theory, can nevertheless be an important teaching tool in helping communicate it to other people. For example, Bohr’s conceptualization of the atom in terms of electrons circling around the nucleus “like a miniature solar system” was the model of atomic structure for generations of students. However, models are analogies. Like other analogies, models are comparable to the phenomena they describe only so far, and no further. Attempts to determine how far an analogy holds often suggest new hypotheses to test or new ways to test old hypotheses. The planetary model of atomic structure is a case in point. With the development of quantum physics, it became clear that the solar system model was inadequate to explain the behavior of subatomic particles. Scientific theories are tentative. Even the best-cherished theoretical models can be supplanted by other models—either because an important hypothesis is falsified or because a more satisfactory explanation or model is proposed. John A. Moore, an embryologist and science historian, stated that “great art is eternal, but great science tends to be replaced by even greater science.”Most theoretical models describe observable events in terms of underlying causes described in the special language of the theory. Atoms, for example, are described by a theory that explains much of the observable behavior of matter, and heredity was explained in terms of genes long before anyone really knew what genes were. Theoretical concepts are typically studied in terms of their observable effects: the properties of matter are described in terms of atoms, and heredity is described in terms of inherited genes. A scientist who describes heredity in terms of genes may never observe those particular genes, but the theory allows her to make further predictions regarding animals or plants and their inherited characteristics. In science, calling something “theoretical” simply means that, even if we cannot directly observe it, we can use the theory to make predictions and study the observable effects.A theory describing the properties of living systemsAnimals, plants, and bacteria are examples of living systems that share many properties distinguishing them from nonliving systems. Each of these properties was initially a hypothesis about how living and nonliving systems differ. Each has been repeatedly tested and verified by observation across a wide variety of organisms, compared with various nonliving systems.Properties shared by living systems, and the testable hypotheses about those properties, may be summarized as in Table 1.1 and listed as follows:Organization. The fundamental unit of life is called a cell. All living systems are composed of one or more cells.Metabolism. Living systems take energy-rich materials from their environment and release other materials that, on average, have a lower energy content. Some of the energy fuels life processes, but some accumulates and is released only upon death.Selective response. Living systems can respond selectively to certain external stimuli and not to others. Many organisms respond to offensive stimuli by withdrawing. Living organisms can distinguish needed nutrients from other chemicals and use only certain chemicals from among those available in their surroundings.Homeostasis. Living systems have at least some capacity to change potentially harmful or threatening conditions into conditions more favorable to their continuing existence, e.g., by converting certain toxic chemicals into less harmful ones.Growth and biosynthesis. Living systems go through phases during which they make more of their own material at the expense of some of the materials around them.Genetic material. Living systems contain hereditary information derived from previously living systems. This genetic material is a nucleic acid (either DNA or RNA) in all known cases.Reproduction. Living systems can produce new living systems similar to themselves by transmitting at least some of their genetic material.Population structure. Living organisms form populations. Populations can be defined retrospectively as groups of individual organisms related by common descent. Among organisms capable of sexual processes, a population is all those organisms that can interbreed with one another.Implicit in this listing of properties is also the testable assertion that anything that is alive by one criterion usually meets the other criteria as well. As new organisms were discovered, each of the above hypotheses has been tested further and sometimes modified. For example, “breathing” was once considered an essential property of life, but this was modified several times to include other forms of gas exchange and metabolism. The invention of the microscope, in about 1700, led to the discovery of bacteria, which caused us to expand our concepts of selective response and led to the cell theory in the 1830s. The discovery of viruses early in the twentieth century strained this theory even more: seven of the eight hypotheses apply, yet viruses are not cellular and cannot reproduce on their own—they must use the cellular machinery of other organisms toreproduce themselves.Together, these hypotheses form a working theory about the characteristics of living things that continues to be productive and to suggest new hypotheses to test. They are not rigid definitions that must be met. If something lacks one of the properties of life, we would not be forced to define it as nonliving; we could instead modify the hypotheses to define the limits of life more precisely. Viruses, for example, fulfill many of the properties of life but cannot reproduce without the help of another organism. We may therefore need to modify the criterion of reproduction to say that living things can bring about or can direct the production of new living things similar to themselves.The above hypotheses have been tested in a wide variety of living systems. We can therefore gain confidence that the properties summarized in Table 1.1 form a coherent theory about how living systems differ from the nonliving.THOUGHT QUESTIONSIn a group, discuss the hypothesis shown in Figure 1.1. Is it testable? If you believe so, then explain what sorts of observations you would make to test it.Scientists seek to provide evidence to ‘support’ hypotheses. Why don’t scientists say that their evidence ‘proves’ hypotheses?Which of the following are experimental tests, and which are naturalistic observations?Measurements made on the bones of an extinct species are compared with similar measurements made on the bones of a related living species.The activity of white blood cells in a blood sample taken from stressed rats is compared with the activity of white blood cells taken from unstressed rats.A group of animals is fed a certain chemical to see whether they will get cancer as a result.A list of the species found in a particular square meter near the coast is compared with another list of species found 20 meters farther inland.Viruses strain any definition of living systems: they contain genetic material, yet they replicate only inside the cells of and with the help of some other organism.Should we think of viruses as alive and devise a theory (or definition) of life that includes them, or should we think of them as lifeless and devise a theory (or definition) that excludes them? Would one of these theories be right and the other wrong, or are we free to choose either option?Scientists Work in Paradigms, Which Can Help Define Scientific RevolutionsIn a book that was itself considered revolutionary when it was first published in 1962, Thomas Kuhn, a philosopher and science historian, proposed a new method of looking at the ways in which science accommodates to new discoveries. Kuhn’s observations were based on his studies of historical revolutions in science.Paradigms and scientific revolutionsAccording to Kuhn, everything that we have described thus far is part of normal science, science that proceeds by the piecemeal discovery and gradual accumulation of new but small findings. Normal science in Kuhn’s theory is always channeled by what he calls a paradigm (pronounced ‘para-dime’). A paradigm is much more than a theory; it includes a strong belief in the truth of one or more theories and shared opinions as to what problems are important, what problems are unimportant or uninteresting, what techniques and research methods are useful, and so on. The research methodology and sometimes the instrumentation are important parts of the paradigm. Normal science proceeds cumulatively, in small steps, within the context of an existing paradigm. Paradigms, according to Kuhn, are best represented by science textbooks, which are written for the purpose of training new scientists within the paradigm. Students trained by these textbooks are taught not just facts, they are taught attitudes, approaches, values, and a vocabulary that teach them to think in certain ways.Once in a great while, says Kuhn, science proceeds in a very different way: a scientific revolution occurs and is marked by the emergence of a new paradigm, which often requires replacement of an older one. Few scientists educated in the old paradigm support the new one at first. Most support for the new paradigm comes from new scientists just beginning their careers, and the founder of the revolution is usually either young or a new entrant into that particular scientific field. Once a scientific revolution occurs, its new paradigm opens up a new field of investigation or rejuvenates an old one. Such an infrequent event is called a paradigm shift. Scientists will not be attracted to a new paradigm unless they feel that it is somehow superior to the old paradigm, usually because it explains a wider variety of phenomena or because it explains certain new findings better than the old paradigm did. Often the vocabulary terms of the old paradigm are redefined or newer terms are adopted; terms that are no longer useful to the new paradigm may be abandoned. A paradigm shift is not just a triumph of logic or of experimental evidence. It is decided, at least in some measure, by a political-style process in which allegiances and influences shift. New paradigms succeed when scientists find them to be fruitful or productive of new approaches to research. Some examples of paradigm shifts are given in Table 1.2.Paradigms are sometimes so powerful as to allow anomalies—observations that ‘do not fit’—to be ignored. To scientists working within a paradigm, anomalies are small problems that they agree to ignore, believing that the integrity and success of the paradigm are more important than trying to accommodate the unexplained anomaly. Scientists who become interested in the anomaly may become founders of their own new paradigms, and the increased attention that they draw to the anomaly may precipitate a scientific revolution. Paradigms become successful in large measure by the students that they attract. Paradigms that no longer attract students die out.Molecular genetics as a paradigm in biologyAs an example of a scientific paradigm in biology, we describe here the field of molecular genetics as it has existed since about 1950. Other examples of scientific paradigms are described in subsequent chapters, including Darwinian evolution in Chapter 5, sociobiology in Chapter 8, and the connection between the mind and the body in Chapter 15.The paradigm of molecular genetics (or molecular biology) emerged in the decades following the determination of the structure of DNA byJames Watson and Francis Crick in 1953. The structure of DNA was itselfsimply a hypothesis that gained rapid acceptance because it explained many known facts and allowed many new predictions to be made. The ‘central dogma’ of molecular biology (so named by the molecular biologists themselves) was that DNA was used to make RNA and RNA was used to make protein. (Further details of this process are described in Chapter 2.) Both DNA and RNA were said to contain information, and the making of one molecule from another was said to be a form of information transfer. As in other paradigms, the central dogma was more than just a theory because it also suggested a new vocabulary and drove a new research program. The language used within a paradigm often reveals much about how the paradigm is understood by the scientists working within it. How did DNA make copies of itself? This was called replication long before any of its details became known. How was information from DNA transferred to RNA? This was called transcription. How was information from RNA transferred to protein? This was called translation. How replication, transcription, and translation occurred were among the major problems to be solved. The terminology in molecular biology, like that in many fields, was part of an elaborate analogy that drew its inspiration from a comparison with linguistics and included such new vocabulary words as code (the language itself) and codons (items in the code). Also, words such as transcription (rewriting within the same language) and translation (changing from one language to another) were deliberately chosen for literal meanings that matched the biological theory. Textbook descriptions were replete with verbs like read, copy, and translate. There were also a number of laboratory methods, inherited from the field of biochemistry, plus a few extra technical advances, such as the use of high-speed centrifuges. Together, this all formed an orderly paradigm that outlined not only what was known, but also what remained to be discovered, what was thought to be important, and how the details were to be investigated and described. DNA was championed as the most important ‘master molecule,’ RNA was almost as important, and protein was important only until its synthesis was completed. Protein that was completely synthesized was no longer deemed interesting, except for a few enzymes that helped in the working of DNA or RNA. The paradigm thus defined the boundaries of the field.The paradigm of molecular genetics guided research on DNA, RNA, and protein synthesis throughout the 1950s and 1960s; much of the work begun in those decades continues today. For its workers, the paradigm defined a set of shared beliefs (including the central dogma), a vocabulary, a set of research techniques, and, most of all, a set of problems to be solved. These problems included the mechanisms by which replication, transcription, and translation took place, as well as how to crack the genetic code. Once this last problem had been solved, the ‘coding dictionary’ (i.e., the list of correspondences between RNA sequences and protein sequences) was given a prominent place in every genetics book and most general biology texts.As the molecular genetics paradigm matured, some of its early tenets were modified. Information flow, once thought to be unidirectional, is now thought to be more complex, sometimes flowing in both directions. Also, the idea of ‘master’ molecules that ‘make’ or ‘control’ other molecules is slowly being replaced by a vocabulary that speaks in terms of cells ‘communicating’ with other cells (sending and receiving signals) or ‘influencing’ other cells (in both directions). Likewise, attention has shifted to new questions, such as how the environment of a cell influences that cell to transcribe certain portions of its DNA at certain times. Still more recently, technological advances have permitted the rapid determination of many DNA sequences, including the sequencing of whole genomes, which has allowed some new questions to be raised. The molecular biology paradigm, like other paradigms before it, has gradually changed over time, although its core beliefs remain unshaken.The scientific communityIs science something that only scientists can do? On the contrary, many people use scientific methods in their everyday lives. For example, if my car fails to start, I might formulate one hypothesis after another as to the possible cause. To test the hypothesis that the car is out of gas, I would examine the gas gauge. Additionally, I could add some gasoline to the tank and then try to start the car. If the car starts, I conclude that it was out of gas. The Swiss child psychologist Jean Piaget has written that children often behave as little scientists, formulating possibilities (hypotheses) in their minds and then testing them. “I can take the toy away from my little brother” can be tested by trying to take it away; the hypothesis would be falsified if brother successfully resisted or if an adult intervened. It is unusual for a single person to formulate a hypothesis, test it, and then critically evaluate the results. For this reason, it is important for scientists to communicate with one another so that all these steps can be performed. Early written examples of hypothesis testing are found in the writings of the Greek historian Herodotus (fifth century B.C.). Early scientists in China, India, and elsewhere also wrote down their ideas by hand, but the spread of printing using movable type greatly speeded up the spread of scientific ideas after about 1500 A.D. Early European scientists (Copernicus, Galileo, Harvey, Descartes, Newton, and others) wrote their ideas in the form of books, pamphlets, and private letters. A major advance, however, occurred in seventeenth-century England, with the founding of the Royal Society in about 1660. This marked the first time in history that a permanent, organized community of scientists had communicated with one another and shared their results in a scientific journal (Philosophical Transactions). Now there was a written and permanent record of experiments performed and conclusions reached—a shared record that encouraged scientists to check one another’s work in a systematic way. Because of this written record, scientists of the past continue to be part of the scientific community when their ideas are tested, even generations later. The scientists shown in Figure 1.4, whose accomplishments are each described elsewhere in this book, are still part of this scientific community even though they published over a time-span ofabout 150 years.Many of the ways in which today’s scientists behave toward one another may be viewed as efforts to maintain their ability to do the kind of systematic checking described above, including the ability to test hypotheses. Every test must be conducted in such a way as to make it possible for the hypothesis to be falsified, if indeed it is false, and the testing of hypotheses should be described as publicly as possible so as to permit the test to be repeated by other scientists. As David Hull points out, “Scientists rarely refute their own pet hypotheses, especially after they have appeared in print, but that is all right. Their fellow scientists will be happy to expose these hypotheses to severe testing.” (D. Hull. Science as a Process. Chicago: University of Chicago Press, 1988, p. 4.) Skeptics who doubt a particular result unless and until they have seen it themselves can best be won over by a tradition that allows them to hear about repetitions of the test or to repeat the test themselves and to make their own observations. For example, Galileo, the astronomer and early scientist, invited critics who doubted his observations to look for themselves through his telescope.So, the process of science is conducted in the public forum as well as in the laboratory. The publishing and dissemination of results (both in print and increasingly on the Internet) and the repetition of observations and experiments by others are thus valued among scientists. This is why the human genome sequence and an increasing number of scientific journals are available through the Internet. Scientists are expected not to work in isolation, but to discuss their results with other interested scientists, allowing them to build upon the results of previous scientists. They can repeat experiments and confirm the results, but they do not need to start from scratch and repeat all earlier work in their field. Science is a cumulative process in which it pays for individual scientists to begin with some of the groundwork laid by others, rather than to start always from scratch. As Isaac Newton once said, “If I have seen further than others who have gone before me, it is because I have stood on the shoulders of giants.”Charles Darwin (1809—1882), evolutionary biologist. Darwin s theories are described in Chapter 5.Gregor Mendel (1822—1884), botanist and geneticist. Mendel s experiments in genetics are described in Chapter 2.Barbara McClintock (1902—1992), agricultural geneticist and Nobel Prize winner. Some of her contributions to genetics are described in Chapter 2.Luis W. Alvarez (1911—1988), Nobel Prizewinning physicist, and Walter Alvarez (1940— ), geologist. Walter s right hand rests on a layer of clay 65 million years old, at the boundary between the Age of Reptiles and the Age of Mammals. The Alvarezes hypothesis to account for the extinction of dinosaurs and many other species across this boundary is described in Chapter 18.THOUGHT QUESTIONSWhy is it so difficult for a scientist to work outside the prevailing paradigm? Give at least three reasons.In what ways is the paradigm of molecular genetics more than just a scientific theory?Many companies conduct what they call research and development, yet many of these companies zealously guard their results and do not publish them. Are they doing science?Researchers have deciphered the complete genetic blueprints of over 800 viruses and many disease-causing bacteria. These sequences are available on the Internet.How might free access to the genetic make-up of disease-causing pathogens be used? How could it be abused?Scientists Often Consider Ethical IssuesScience itself can never tell us whether certain research should be done or how the results should be used by society; for those answers we turn to the branch of philosophy called ethics. Many topics in this book have an ethical dimension. Are some applications of specific biological research morally right and other applications morally wrong? Should society place legal restrictions on scientific research? Should biologists concern themselves with the ethics, applications, and implications of their work? This section describes some of the ways in which individuals and societies make ethical decisions.We each use beliefs concerning what is right or wrong, proper or improper, to guide our own behavior. It is right to come to class at the scheduled time and in general to keep appointments that one has agreed to. It is wrong to steal, to lie, to murder, or to park in the NO PARKING zone. It is proper to wait for the traffic light to turn green and to wait for one’s turn in line. All these moral rules, or morals, are products of societies. Anthropologists who have compared societies from around the world tell us that moral rules differ from one society to the next; they also change over time as society changes.Any personal decision about whether to follow a moral rule may be called a moral decision: for example, should I park in the NO PARKING zone? Moral decisions are often made with the knowledge that society will attempt to enforce the rules with penalties or sanctions. Formal sanctions include fines and jail time; informal sanctions, which operate more often, include being criticized or avoided by others and ending up with fewer friends.EthicsEthics is a discipline dealing with the analysis of moral rules and the ways in which moral judgments are made and justified. Descriptiveethics, the study of how these judgments are actually made, is a social science that investigates human behavior using scientific methods. In contrast, normative ethics, a branch of philosophy, deals with the logical analysis of how ethical judgments should be made, an analysis for which observational data are insufficient—no data can either confirm or refute a moral law (such as “Thou shalt not kill”). In its simplest form, normative ethics is an attempt to reduce moral codes to a minimum set of basic rules (maxims). For example, I should come to class on time because my signing up for a course is like making an appointment. Appointments should be kept because they are promises or contracts. An ethic of keeping appointments is part of a larger ethic of keeping promises.Some rules of conduct are simply inventions of a society for the convenience of its members, such as waiting for the green light, driving on the right side of the street (in North America), and the observing of NO PARKING zones (Figure 1.5). We cannot all drive through the intersection at the same time, and traffic lights are a convenient (if arbitrary) contractual way of arranging whose turn is next. The contractual nature of such agreements is obvious because there are usually publicly controlled processes (like city council meetings) to decide where to put NO PARKING zones. We promise to observe traffic laws when we apply for a driver’s license, so following these laws may be viewed as another form of promise keeping.Waiting one’s turn in a line or waiting for a green traffic light areboth ways of introducing order and fairness into a situation that would otherwise be chaotic and conducive to unnecessary disputes. A major difference, however, is that waiting one’s turn in line is not enforced by law or traffic code. It is enforced informally by the tacit agreement of those who are present.A simple moral code might therefore instruct us to keep our promises, not to interfere with the rights of others, and to observe the common social conventions. This could easily be expanded into a more general code of benevolence, cooperation, and mutual aid.Resolving moral conflictsThere are occasions when conflicts arise within sets of moral rules. I know I should obey the traffic laws, but what if I am taking an injured person to the hospital and the person’s life is in danger? Does the duty to save a life justify driving above the speed limit, driving through a red light, or parking in a loading zone? Can I justify disobeying traffic laws to keep an appointment? Does it matter how important I think the appointment is? Resolving conflicts of this kind is one of the major goals of ethics.In most cases, the resolution of such moral conflicts is made by determining that one rule or goal is more important than another: saving a life is more important than obeying traffic rules, for example.Figure 1.5Would you park in this space? Give reasons to explain your decision.Thus, there are exceptions to most moral rules: obey traffic rules and other useful conventions except when obeying them causes greater harm or violates a more important rule. Notice that this ranks certain rules as more important than other rules, allowing us to justify an exception to one rule by invoking a ‘higher’ rule.Although ethics is a branch of philosophy, ethical arguments arise in everyday life and also in science. For example, a scientific researcher may have financial interest in the success of a particular company, which might create a bias in scientific research regarding that company’s products.More and more scientific endeavors are raising ethical issues that are of practical interest to people in all walks of life. Virtually all institutions that conduct research now have policies and procedures for managing conflicts of interest. The U.S. government has sponsored research, meetings, and publications in the field of biological ethics. Many governmentprograms, notably the Human Genome Project (see Chapter 4), have set aside portions of their budgets for the examination of the ethical implications of science. Our grounding in ethics in this chapter will support our examination of many issues with far-reaching ethical implications in the chapters that follow.Deontological and utilitarian ethicsAn ethical system is a set of rules for resolving ethical questions or for judging moral rules. Of the many possible ethical systems, we will describe the two major types that have received the most attention and attracted the most followers. Other ethical systems are described on our Web site, under Resources: Other ethical systems.Deontological systems. An ethical system is called deontological if each person has a duty to perform certain acts and to avoid others, but the rightness or wrongness of an act depends on the act itself and not on its consequences. To a deontologist, the wrongness of murder is in the act itself, not stemming from its results or its effects on society. Similarly, a deontologist who believes in keeping promises does so apart from any consequences.Historically, most deontologists have developed moral codes based on religious traditions. The Bible, the Koran, and the sacred texts of other religions have been the source of many moral codes. People who share the same religious tradition can often reach agreement quickly under such a system. But a deontological system based on a particular religion may have less influence on people not belonging to that religion. The German philosopher Immanuel Kant (1724–1804) devised a deontological system without a religious basis. Kant based all ethical statements on a single precept: act only according to rules that you could want everyone to adopt as general legislation. He called this rule the categorical imperative. His test of the morality of an act is whether the act can be universalized, that is, applied to all people at all times. Thus, killing is (always) wrong because I could not possibly want people always to kill one another—I would be willing my own death and the death of my loved ones. Keeping promises can be universalized, and promise-keeping is therefore (always) moral. Respect for all human beings is an important part of Kant’s system, and fundamental rights are basedon respect for the dignity and autonomy of all persons. If you respect the dignity of all human beings, then you cannot ever will the death of any person, nor can you deny them their fundamental rights, nor can you use them as objects for your own personal gratification in any way. If you respect their selfhood, then you cannot morally abridge their freedom.There has been considerable disagreement among philosophers, and even more variations in historical practice, over the types of beings to which various rights apply. At various times in the past, certain groups of persons (including women, children, slaves, the lower classes of stratified societies, impoverished people, foreigners, members of various races, mental patients, and persons unable to speak for themselves) were denied the rights that were afforded to other members of society (Figure 1.6). Many people now invoke dignity and autonomy criteria in discussions of whether certain rights should also now be extended to unborn fetuses or to animals.An argument against rights-based deontology is that there are many circumstances in which one right conflicts with another, resulting in a moral dilemma. Unless there is a clear way of deciding between conflicting rights, moral dilemmas are inevitable. An obvious way out is to declare one particular right (such as the right to life or the right to freedom of action) supreme over all others. Aside from the problem that different deontologists would choose different rights to take precedence over the others, there is the more serious objection that insistence on a single right leads to the dangers of absolutism. Historically, many atrocities have been perpetrated by the followers of systems that put absolute adherence to a single principle above all others.Utilitarian systems. A utilitarian system of ethics is one in which acts are judged right or wrong according to their consequences: rightful acts are those whose consequences are beneficial, whereas wrongful acts are those with harmful consequences. To a utilitarian, murder is wrong because the death of the victim is an undesirable outcome under most circumstances. Also, on a larger scale, murder is additionally wrong because it produces a society in which people live in fear.A challenge to all utilitarian systems is to find a way of measuring the goodness or badness of consequences. Over the years, utilitarian philosophers have come up with different criteria by which to judge consequences: the greatest happiness for the greatest number of individuals, the greatest excess of pleasure over pain, and so on. All utilitarian systems require that value judgments be made between outcomes that are difficult to measure and quantify (Figure 1.7).Utilitarianism can be summarized by the rule “always act so as to maximize the amount of good in the universe.” The first major utilitarian philosopher was Jeremy Bentham (1748–1832), who said that we should always strive to bring about “the greatest good for the greatest number.” To decide which actions produce the greatest good, Bentham suggested a type of cost–benefit analysis that he called “aFigure 1.6Do you have a deontological reason for agreeing or disagreeing with the premise that all persons share the same basic rights? This woman was protesting the fact that U.S. President Woodrow Wilson supported the rights of poor Germans in World War I, while women in the United States were denied the right to vote.Figure 1.7What benefits could come to society from this nuclear power plant? What costs or risks are present? How would a utilitarian argue in favor of this power plant?How might another utilitarian argue against it?calculus of pleasures and pains.” Other notable utilitarian philosophers include John Stuart Mill (1806–1873) and G.E. Moore (1873–1958).One of the major criticisms of utilitarianism is that its cost–benefit approach reduces the status and dignity of human beings, and in some cases violates their rights. Can the killing of one person be justified if it results in saving the lives of other people? Deontologists argue that certain individual rights must be protected regardless of whether society as a whole benefits. To do any less, they argue, deprives human beings of their fundamental dignity as individuals and makes them nothing more than a cluster of costs and benefits. Even if a larger benefit can bedemonstrated in a given instance, say these critics, it is still unethical to violate an individual’s fundamental right, because “the ends do not justify the means.”Ethical decision-makingIndividuals who are faced with moral choices are ‘moral agents,’ meaning that they are held responsible for their decisions and are praised for good decisions and criticized or punished for bad decisions, at least in a just world. Scientists are moral agents because they encounter moral decisions in their work. Science has also presented society at large with moral choices concerning the ways in which the findings of science may be used. Some moral decisions are left up to individual choice, while other decisions are madeby institutions or by society as a whole. Many moral decisions involve conflicts between the rights and interests of individuals and the broader interests of large institutions or of society at large. Decisions that affect many people at once are usually made collectively, at least in a democracy, and many people may seek to influence such collective decisions.Individuals making moral choices are often guided by principles of duty or moral imperatives, such as those listed in Table 1.3.In facing a moral decision, a person using deontological reasoning asks, “what are my duties?”. If several duties are in conflict, the question then becomes, “which is the more important or higher duty?”. In a utilitarian approach, the costs (or risks) and benefits of each possible choice must be compared, including the example that may be set for others. The question then becomes, “which set of costs and benefits is preferable?” meaning “which set achieves a maximum of benefits at a minimum of costs?”In the case of a moral dilemma—where no option is entirely good— we often seek further guidance in reaching a decision. The following procedural steps can help us in reaching moral choices: (1) gather all the facts and check them for correctness; (2) identify the ethical problem; (3) identify all the parties (stakeholders) that would be affected; (4) analyze the problem (e.g., with a deontological or utilitarian approach);present the alternatives in priority order; (6) make and implement the decision; (7) if possible, reevaluate the decision as its consequencesunfold. On our Web site we have included ethical case studies for you to consider (under Resources: Ethical discussion topics). You may wish to refer to these steps to help you complete the assignments, or to help make moral choices in the real world.Collective ethical decisions. Moral choices are in many cases made by groups of people rather than by individuals. These groups can be legislative bodies, professional groups, or private corporations. Many of these choices can affect large numbers of people or society as a whole. Individuals have an important role in such group decisions; however, the decisions made by a particular group can sometimes conflict with one’s own self-interest or one’s own moral judgment. How, then, should ethical choices be made by collective groups?In culturally homogeneous societies in which people share common values and religious beliefs, it may be possible to reach consensus about which acts are wrong and which are right. However, most societies today are pluralistic in the sense that their populations include people with differing cultural and religious backgrounds, who are likely to be diverse in their opinions, values, and ethical approaches. Reaching collective decisions on ethical issues is more difficult in pluralistic societies, most ofwhich are democracies or are becoming more democratic. We therefore examine how people in modern pluralistic democracies reach agreement on issues with moral dimensions.In a pluralistic society, some people come to the public forum with utilitarian assumptions, others come with deontological assumptions,and others may have different positions. Even within these ethical tradi-tions, people differ in their outlook: utilitarians have differing evaluations of costs and benefits, and deontologists have differing rankings of rights. One way of reconciling these different views is to have a public debate (so that all views are heard) and then vote. The voting procedure should be structured in a way that all parties recognize as fair. Fairness is the principle that states that all people should be treated impartially and equally; it is a way of ensuring that rights are not violated. In most cases, a system that works in this way results in the least displeasure with the decision. Of course, total agreement on a decision is hard to achieve in any large pluralistic society.Social policy includes all those laws, rules, and customs that people follow in making individual decisions in a society. The making or changing of a new social policy is called a policy decision. Most social policies and policy decisions involve ethical considerations. An increasing number of policy decisions also involve some aspect of science, and it is often convenient to divide these into three phases: scientific issues, science policy issues, and policy issues.Scientific issues. What possible explanations (hypotheses) exist that might explain the available data? Can these hypotheses be tested? Do the tests support or falsify each hypothesis? Are alternative explanations available? What additional data are needed to evaluate these hypotheses? These are often characterized as ‘purely’ scientific issues on which scientists of different political or ethical persuasions may be expected to agree if sufficient data are available.Figure 1.8Why do people have a right to express their opinions through public demonstrations like this one? What role do such public demonstrations have in shaping social policy?Science policy issues. What would be the consequences of this or that particular legislation or policy change? What would be lost or gained from each proposed plan of action? Can the probability of uncertain consequences be estimated? The probability of any outcome, especially one not desired, is called a risk. Can we calculate or estimate the risks? In a cost–benefit analysis, what are the costs and what are the benefits? How certain are we of the estimated values? These are still scientific issues in the sense that they are evaluated from data, but disagreements on the data or their significance are expected between experts with different political or ethical viewpoints. If the experts disagree, how shall we evaluate their respective positions?Policy issues. Once we have evaluated the possible consequences of various possible policies, which one should we choose? These are ethical decisions in which values have a prominent role (e.g., is it worth risking the disruption of the economy to stop global warming?). In general, is some predicted but uncertain benefit worth the calculated risks? If a proposed change can be made only by incurring a certain cost to society, is this social cost worth the intended benefit? In all these cases, the cost–benefit analysis is used not to make the final decision, but rather to provide the necessary data on which a policy decision can be intelligently based.Who makes the decisions? In most societies, scientific issues are frequently decided by scientists with little input from interested citizens. Science policy issues are often decided in the court of public opinion by an interplay of scientists and other ‘experts’ under the scrutiny of policy advocates for one side or the other. Public discussion and disclosure of evidence is useful in exposing and eliminating faulty information. Although evidence is used, it is more like courtroom evidence, obtained and evaluated by cross-examining witnesses, than like the evidence of science, obtained by the formulation and testing of alternative hypotheses.As for the final policy decisions, who makes them: the scientists, the public, the media, or the government? In most democracies, the deci-sions are made either by the public or by government agencies acting (in theory at least) in the public interest. Decision makers are often influenced by scientists, the media, particular interest groups, and public pressures of various forms—marketplace decisions (decisions by individuals about where to spend their money), letters and e-mailings, organized demonstrations (Figure 1.8), enthusiasm at public gatherings, public opinion surveys, and direct votes on referendum questions. All of these influences certainly have a role in what is essentially a political process.Together with other students, make a list of five to ten laws or rules that are generally followed on your campus or in your community. For each, try to discover:Why such a rule is considered important (or why it was considered important when the rule was adopted),Whether there is a more general moral concept of which this rule is just a special case, andWhether society is better off with rules of this general kind than without them, and, if so, why?Try to justify the wrongness of the following acts under the two ethical systems discussed in this section:
Murder
violation
bank robberyfailure to repay a debtracial segregationTHOUGHT QUESTIONSdriving over the speed limitparking in the handicapped space shown in Figure 1.5 if you are not handicappedWhich ethical system makes it easy to explain the wrongness of these acts? Under which ethical system are these explanations difficult?A scientist is paid by a drug company to test a new drug for safety and effectiveness. What are her duties to the drug company? What ethical conflicts might arise? What safeguards are needed? Does it make a difference if she owns stock in the drug company?What scientific issues are raised by the nuclear power plant pictured in Figure 1.7? What science policy issues? What data would you seek on which to base a policy decision one way or the other?Ethical Questions Arise in Decisions About the Use of Experimental SubjectsSo far we have discussed ethical issues in very general terms. We now turn, for illustrative purposes, to a specific issue, the use of experimental subjects in biological research. This issue involves moral choices at all the levels we have discussed: individual, institutional, and societal. First, we consider animal rights and the uses of animals in scientific experiments. Second, we contrast animal experimentation with experiments on humans. Of the many ethical issues surrounding biology today, few are as divisive as those touched upon here.Uses of animalsHuman societies have kept animals at least since the origin of agriculture. There are few societies in which animals are not kept as food, as pets, or as workmates. Most societies that practice agriculture use animals for all three purposes. Love of animals and use of animals can go hand in hand.By far the largest number of animals used by most societies are raised for consumption as food for humans. Animal products are used for clothing. Animals are also the targets of recreational hunting, fishing, and trapping, even in many industrial societies. Many people keep pets or ‘companion animals.’ Work animals pull and carry loads, help in police work, and help handicapped people. Finally, animals are often used in research, although the number is only a tiny fraction of the numbers consumed as food.Nearly all new drugs, cosmetics, food additives, and new forms of therapy and surgery are tested on animals before they are tested on humans. Many people regard animal research as critical to continued progress in human health. Over 40 Nobel Prizes in medicine and physiology have been awarded for research that used experimental animals. Organ transplants, open-heart surgery, and various other surgical techniques were performed and perfected on animals before they were performed on humans. All vaccines were tested on animals before they were used on human patients. In most cases, animals are used in research as stand-ins for humans. If we did not use animals for these purposes, humans would be the experimental subjects tested. Most animal testing is limited to the initial development of a drug or surgical procedure, but the human benefit continues for many generations or longer.Few people object to a use of animals that saves human lives. Most people also agree that animals should not suffer unnecessarily, whether they are pets, work animals, or research subjects. Scientists need to use healthy, well-treated animals in research, and the U.S. Guide for the Care and Use of Laboratory Animals reflects this concern. There are standards such as cage sizes that must be followed by scientists using animals. All research using live animals must, by law, be scrutinized and approved by supervisory committees, and the committees require the investigators to minimize both the number of animals used and the amount of pain that those animals experience, and to substitute other types of tests where possible. According to statistics from the U.S. Department of Agriculture, 62% of animals used in research experienced no pain, and another 32% were given anesthesia, pain killers, or both, to alleviate pain. Only 6% of animals suffered pain without benefit of anesthesia. Federal law in the United States requires the use of anesthesia or pain killers in animal research wherever possible. Exceptions are allowed only when the use of anesthesia would compromise the experimental design and when no alternative method is available for conducting the test.The animal rights movementThose concerned with animal rights vary from traditional humane societies such as the Society for the Prevention of Cruelty to Animals (S.P.C.A.) and various national, state, and local humane societies, through groups such as People for the Ethical Treatment of Animals (PETA, founded in 1980), to groups such as the Animal Liberation Front (ALF, founded in 1972). Some animal rights advocates use a utilitarian ethic to advocate their position; others are deontologists.Do animals have rights? Bernard Rollin, an American philosopher who supports animal rights, argues that there is no good reason for drawing an ethical distinction between mentally competent adult humans, other human beings (including children, comatose patients, mentally ill or brain-damaged persons), and animals. Animals are therefore, in his view, worthy of any moral consideration that would normally be given to babies, comatose patients, and other people unable to speak for themselves or to articulate their own viewpoints.Historically, animals have been treated legally as property. Animal owners have property rights such as the right to sue for damages if their animals are killed or injured, but the animals themselves have no legal rights. Many philosophers have attempted to justify this approach by asserting that animals cannot be held morally responsible for their actions and are therefore not moral agents. Only moral agents are considered to be capable of entering into contractual agreements or of having any rights. The question of animal rights is actually part of a broader question: how far do we extend the scope of any rights that we recognize? Many societies have historically denied even the most basic of rights to certain classes of persons on the basis of economics, gender, race, ethnicity, or religious beliefs. The extension of certain basic rights to all humans, including children and convicted criminals, is now considered so fundamental to the ethical sensibilities of most people that we refer to these as human rights. International agreements, such as the Geneva Convention on the treatment of prisoners of war and the International Convention on Human Rights (the Helsinki Accord), attest to the importance given to these human rights in world affairs. But should we stop there? Animal rights advocates say that we should extend these same rights to all beings capable of sensing pleasure and pain. A few people go even further, asserting that even trees have such rights as the right to go on living or not to have their air and soil poisoned. To go still further, a few people assert that habitats themselves, including mountains and forests, haverights not to be despoiled.This book’s Web site (see Resources: Animal rights) contains further discussions about animal rights and the use of animals in experiments.Humans as experimental subjectsMany animal experiments are undertaken to determine the effects of some new drug or other therapy. The real question is usually about what the effects would be in humans, and the animals are merely used as stand-ins. Is it safe to extrapolate to humans results obtained from nonhuman species? In most cases in which data are adequate to answer this question, human physiological reactions have turned out to be comparable to those of experimental animals. Even when differences between humans and other species are known, they are often known in sufficient detail that the different responses to testing can help us understand the human system better, which still makes the animal tests valuable.A few instances are known in which humans and certain commonly used experimental animal species respond differently. Saccharin, for example, causes cancer in rats, but has never been shown to cause harm to humans.Direct experimentation on humans avoids the question of comparability between species, meaning that the results can be used more directly than results obtained from other species. Also, results obtained from psychologists, epidemiologists, and others who study humans with naturalistic methods can be applied even more directly. For example, one could not ethically force-feed cholesterol to an experimental group of human subjects, but one could observe the diets that different people choose on their own and study how people with high-cholesterol diets differ from people with low-cholesterol diets. The diets in such a study are more directly comparable to the diets of other humans than are those of experimental animals fed with different amounts of cholesterol in their food. As explained in many later chapters, more than one type of method must be applied to answer many scientific questions. We should not view animal studies versus naturalistic studies of humans as either/or choices; in most cases, both approaches are needed.Among possible experimental subjects, humans have a special status. On the one hand, inflicting pain on human subjects, or exposing them to experimental risks, raises more ethical objections than does the similar treatment of nonhuman animals. On the other hand, human subjects can tell us how they feel, or when and where they experience discomfort or pain. Certain types of drug side-effects, like headaches or impairment of problem-solving ability, are difficult to assess without using human subjects.Voluntary informed consent. A purely ethical consideration is that human subjects can voluntarily consent to serve as experimental subjects, which is something that nonhuman animals cannot do. Humans are considered to be autonomous beings who have the right to consent to putting themselves at risk, whether in a space capsule, a bungee jump, or an experiment. An important consideration, however, is that the person serving as a subject must give consent voluntarily. This is a legal as well as a moral issue, because persons who did not consent voluntarily can sue for damages if any harm comes to them. Consent is usually obtained in writing on a form that informs the person of the possible benefits and risks of the experimental procedure and is therefore called informed consent. If an experiment may bring direct benefit to a subject (as when a disease or its symptoms are being treated), potential subjects may be more willing to undergo certain risks than they would otherwise.Special questions arise in the case of persons who may not have the full capacity to understand all the possible risks and benefits, including mentally deficient persons, unconscious persons, or children. Most people would now consider it unethical to use such a person as an experimental subject unless there was obvious great promise of direct benefit and only minimal risk of harm. In most jurisdictions, parents are considered to have the legal right to make such decisions on behalf of their children. In past decades, prison populations were often used as sources for experimental subjects, but this practice is now frowned upon because the consent of a prisoner may not be truly voluntary if she or he thinks—rightly or wrongly—that cooperating might result in a sentence reduction.Guidelines for human experimentation. As a safeguard against possible abuses, research on human subjects is now usually reviewed by institutional committees set up for that purpose. As is true in reviews of animal experimentation, the review process ensures that someone other than the researchers evaluates the ethics of the proposed experiment. Federally sponsored research in the United States and in many other countries requires that such committees authorize all experiments in which humans are used as subjects. In addition to ensuring that proper voluntary consent has been obtained, such committees also have the obligation to suggest ways in which risks can be reduced or benefits increased without impairing the validity of the experiment. Many scientists work within the ethical tradition in which exposing humans to experimental risks is more objectionable than exposing animals of other species to those same risks. Guidelines have been developed that specify testing to be carried out on animals first, then on small numbers of carefully chosen and carefully monitored human subjects, and only last on large and diverse human populations. In the United States, federally sponsored research and research on new drugs seeking federal approval are required to follow this procedure.Avoiding gender bias. It is now considered poor practice to extrapolate experimental results to both sexes if the tests were done on men only. However, such studies were once fairly common, and many women therefore received drug doses that had been based on studies of men only. Guidelines for human testing were revised only after the ethical issue of gender bias was raised by Dr Bernadette Healy. This is further discussed on our Web site, under Resources: Gender bias.For each of the following acts, try to give:A deontological argument against the actA deontological argument justifying the actA utilitarian argument against the actA utilitarian argument justifying the actbeating your horsetaking a canary into a coal mine so that, if it dies from toxic gases, miners would be warned to evacuateraising broiler chickens or beef cattle for human consumptiontesting a drug on rats (or cats) before giving it to humanstesting a drug on human prison convictsHow widely can experimental results be extrapolated? If a drug is tested on inbred male rats, is it certain that the results are applicable to humans? Is it likely? Is theTHOUGHT QUESTIONSdrug likely to have similar effects on both sexes? What issues of methodology or of ethics are raised by experiments that used only inbred male rats?Is it ethical to infect a few people with a deadly disease to study its effects in the hopes of saving many more lives in the future? How do you justify your answer? Give both deontological and utilitarian reasons.One hundred patients are to be enrolled in a study of a new drug. Half of the enrolledpatients will be given the new drug while the other half will be used as a control and will therefore not receive the new drug.How many of the patients need to give informed consent? Why?Concluding RemarksIn science, we know what we know through a process often called the scientific method. Scientists formulate tentative ideas (hypotheses) about living systems and about the world in general, and submit these ideas to extensive testing by comparing their ideas with observations made in the material world around them. Scientific knowledge is forever tentative and is never ‘proved’ because it is always subject to change if new observations do not fit our existing theories. The language of science is often metaphorical. Scientists often use words with specialized meanings. Scientific paradigms give science its vocabulary, imagery, attitudes, and value judgments. Science is conducted in a social context that includes a community of scientists sharing their ideas and testing each other’s hypotheses.Ethical decisions can be made either by judging actions themselves (deontological ethics) or by judging actions on the basis of their consequences (utilitarian ethics). Science may sometimes confront individuals with moral choices. Many scientific issues have implications for large numbers of people or for society as a whole. All citizens, not just scientists, should help make these decisions collectively. However, scientists should bear some responsibility for educating others about the science issues and science policy issues that can inform these decisions. Scientists should educate themselves as to the ethical dimensions of their work, including both the treatment of experimental subjects and the possible uses and misuses of scientific findings.Chapter SummaryScience is based on the testing of hypotheses under conditions in which it is always possible to observe results inconsistent with the hypothesis.Hypotheses originate by many types of reasoning and inspiration, including both induction and deduction.A group of well-tested hypotheses forms a theory. A theory may be communicated by special vocabulary or by a descriptive analogy (a model).Biology is a science because biologists use hypothesis testing to study living systems.Living systems exhibit cellular organization, growth, metabolism, homeostasis, and selective response. They contain genetic material, and they belong to populations, most of whose members are capable of reproducing.Biologists test hypotheses either by studying natural conditions as they occur (naturalistic science) or by conducting experiments under conditions that the scientists help to create (experimental science). After data are gathered, the interpretation of results usually involves comparison with control groups, often with the help of statistical methods.Normal science proceeds by testing hypotheses one at a time, under the guidance of a paradigm. A new paradigm may replace an older one if it can explain things better than the old one did; such a shift in paradigms brings about a scientific revolution.Scientific methods are used in everyday life, but scientists use these methods more often and more systematically.Certain values are held by members of the scientific community that ensure them the continuing ability to test, falsify and change each other’s hypotheses.Morals are rules that guide our conduct. Ethics is the discipline that examines moral rules and attempts to explain or justify them.Two major types of ethical systems are deontological and utilitarian. Deontologists judge the rightness or wrongness of an act by characteristics of the act itself, apart from its consequences. Utilitarians judge the rightness or wrongness of an act on the basis of its consequences. Utilitarian analysis often includes a comparison of the undesirable effects (costs) of an act with its desirable effects (benefits).Science can confront individuals and societies with moral choices.Individual moral choices can be guided by principles such as nonmaleficence, beneficence, autonomy, and fairness.In facing collective ethical issues involving scientific questions, it is often useful to distinguish between scientific issues, science policy issues, and policy issues.Animals are used in our society for food, for labor, for companionship, and for laboratory experimentation. Biological experiments often use living organisms as subjects. In many cases, laboratory animals are used as stand-ins for humans, and their use is often justified on a utilitarian basis (the cost–benefit ratio is lower if animals are tested before humans) or on a deontological basis (humans have rights and animals do not, or human rights supersede animal rights).Before any experimentation on animals or humans can take place, the proposed experiments must pass an ethics review. If humans are used, their voluntary informed consent must be obtained.CONNECTIONS TO OTHER CHAPTERSThis chapter connects to the remainder of the book because the methods of discovery outlined in this chapter were used to explore all of the topics described in subsequent chapters. The characteristics of life listed at the beginning of this chapter are referred to throughout the book. Also, many applications of science have ethical dimensions, including the following:Chapter 3 The Human Genome Project and human genetic testing raise ethical questions.Chapter 7 Ethical objections have been raised against the ways in which biology has supported racism.Chapter 8 Evolution has resulted in various behaviors, including both moral and immoral acts among humans.Chapter 9 The need for population control conflicts with the ethic of allowing reproductive freedom.Chapter 10 Patterns of food consumption and distribution raise ethical issues.Chapter 11 Some people object to genetically engineered foods on ethical grounds.Chapter 12 Cancer research often involves the use of animal experimentation.Chapter 13 Brain research involves animal experimentation and also the use of fetal tissue.Chapter 14 Drugs are usually tested on animals before giving them to people.Chapter 16 Many ethical issues surround the transmission of AIDS, testing for AIDS, and the prevention of AIDS.Chapter 18 Many ethical issues are raised by habitat destruction and species extinction.Chapter 19 Global patterns of pollution raise ethical issues.PRACTICE QUESTIONSWhich property of life is exhibited by each of the following?The frog jumps around when I touch it.The bread rises because the yeast has given off carbon dioxide bubbles.Blood samples from healthy humans always have about the same pH and salt concentration.Wherever I find one mosquito, I usually find many.Only a few rabbits were brought to Australia, but now there are millions.Puppies usually resemble their parents.Baby animals get bigger and become adults.A bright light at night always attracts moths.Which of the following are testable hypotheses? For each statement that you think is testable, explain what sort of test you might conduct and what possible outcome would falsify the hypothesis.‘N SYNC is a better musical group than the Rolling Stones.In a maze that they have never seen before, rats will turn right just about as often as they will turn left.If these two plants are crossed, approximately half of the offspring will resemble one parent and half will resemble the other.It is wrong to inflict pain on a cat.Restaurant A is better than restaurant B.The average science major at this school gets better grades than the average humanities major.Which of the following examples of reasoning use induction? Which use deduction?If all adult female birds lay eggs, then this female chick will lay eggs if raised to maturity.If all known species of birds are egg-laying, then the next bird species to be discovered will be egglaying too.If all known enzymes are made of protein, and I discover a new enzyme, then it, too, will be made of protein.If the amounts of protein X are increased under stress, then I should be able to increase the amount of protein X in these frogs by subjecting them to stressful conditions.If this species mates in April, then I should be able to observe more mating on April 10 than on June 10.Which of the following reflect the community nature of science?A scientist presenting a talk at a scientific meeting.Another scientist asking a question at that same meeting.A field naturalist tracking a rare species.The same field naturalist publishing her findings.A scientist feeding a new chemical to mice to study its effects.A bacteriologist using techniques developed by Louis Pasteur and Robert Koch for growing bacteria in laboratory cultures.A scientist displaying his experimental results over the Internet.For each of the following, identify (a) whether the argument is based on utilitarian or deontological ethics, and (b) whether any assumptions are made about whether animals have no rights, some rights, or rights equal to those of human beings.Hunting is wrong because the victim is part of nature and it is wrong to interfere with nature.Hunting is justified because the death of one animal makes such a small difference to most hunted species.Hunting is wrong because it makes the hunter more prone to future violence.Hunting is justified if the animal is used as food but not as a trophy.Raising beef cattle for human consumption is justified because people need to eat.Raising beef cattle for human consumption is wrong because cows are sacred.Raising beef cattle for human consumption is wrong because people would be healthier if they ate more plant foods instead.Raising beef cattle for human consumption is wrong because it causes pain and suffering to the animals.Be kind to your pet because you will be rewarded with loving companionship.IssuesHow have our concepts of genes developed?What are the limitations of Mendelian genetics?Does Mendelian genetics explain inheritance in all species?What do we not understand about genes, chromosomes and DNA?The genePatterns of inheritance (trait, phenotype and genotype; sexdetermination; sex-linked traits)Mitosis and meiosisDNA (the genetic material, DNA structure, DNA replication)Human genetic conditions2Chapter OutlineMendel Observed Phenotypes and Formed HypothesesTraits of pea plants Genotype and phenotypeThe Chromosomal Basis of Inheritance Explains Mendel’s HypothesesMitosisMeiosis and sexual life cycles Gene linkageConfirmation of the chromosomal theoryGenes Carried on Sex Chromosomes Determine Sex and Sex-linked TraitsSex determination Sex-linked traitsChromosomal variationSocial and ethical issues regarding sex determinationThe Molecular Basis of Inheritance Further Explains Mendel’s HypothesesDNA and genetic transformation The structure of DNADNA replication33Genes, Chromosomes, and DNAow do offspring come to resemble their parents physically? This is the major question posed by the field of biology called genetics, the studyof inherited traits. Genetics begins with the unifying assumption that biological inheritance is carried by structures called genes. The discovery of what genes are and how they work has been the subject of many years of research. Genes are carried on chromosomes and much has been learned about genetics from the study of chromosomes. Among the earliest findings was the fact that the same basic patterns of inheritance apply to most organisms. The inheritance of some human traits, such as albinism, can be explained by hypotheses first formulated from the study of pea plants, whereas the inheritance of other human traits, such as sex determination, is a much more complicated affair.Mendel Observed Phenotypes and Formed HypothesesNo two individual organisms are exactly alike. Folk wisdom going back to ancient times taught people that a child or an animal resembles both its mother and its father by showing a mixture of traits derived from the two sides of the family. This suggested a concept that came to be called ‘blending inheritance,’ in which heredity was compared to a mixing of fluids, often identified as ‘blood.’ The research that we are about to describe caused this theory to be abandoned.Traits of pea plantsDuring the nineteenth century, Gregor Mendel, a Czech scientist living under Austrian rule, worked out the principles of inheritance for simple traits that he described in ‘either/or’ terms. Mendel was a priest who grew pea plants (Pisum sativum, kingdom Plantae, phylum Anthophyta, also called Angiospermae) in the garden of his monastery. Mendel was curious about differences that he observed among different varieties of pea plants, so he decided to breed them and keep careful records.Why were the peas a good species for Mendel’s experiments? Pea plants have many distinctive traits (Figure 2.1), and other practical advantages: Mendel could easily grow them in the monastery garden, and many varieties were locally available, including some with yellow peas and others with green peas, and some with round and others with wrinkled peas. Mendel knew that peas reproduce sexually—that is, a new individual forms by the union of an egg from a female with a sperm from a male, an event called fertilization. Unlike most animals, an individual plant may have both female and male reproductive organs. This is true of many plant species, including peas (Figure 2.2). Within the pea flower are male structures called anthers that produce pollen grains, each of which contains a sperm. The pea flower also has a female structurecalled a stigma that receives pollen grains (a step called ‘pollination’) and34permits the sperm to travel to the ovary to reach the eggs. Self-pollination occurs when pollen from a plant is deposited on a stigma of the same plant. In some of his experiments, Mendel sewed together the margins of one large petal to enclose the anthers and stigma together and ensure self-pollination. At other times, he cross-pollinated his peas by dusting pollen from a flower of one plant onto the stigma of a flower of another plant, after first removing the anthers from the recipient plant.Mendel organized his work so as to answer specific questions, a procedure that we recognize today as good experimental design. Unlike most of his predecessors who failed to discover how plant offspring inherit their parents’ traits, Mendel followed certain careful procedures:First, for each of the traits he studied, Mendel used peas belonging to pure lines. A ‘pure line’ is one that breeds true from generation to generation, always producing offspring that express the same form of the trait as the parents. For example, tall parents from one pure line always produce tall offspring and short parents from another pure line always produce short offspring.He chose which plants would mate by either cross-pollinating (crossing) the flowers or closing up the flower parts to ensure selfpollination (see Figure 2.2).He first studied only one trait at a time, until he understood its pattern of inheritance. Later, he studied two and three traits at a time. His predecessors, on the other hand, often began by examining several or many traits at once.He counted the offspring of each cross, and was thus able to recognize ratios between them. (Those few of his predecessors whoFigure 2.1The seven traits studied by Mendel in peas.SeedSeedFlowerFlowerPodPodPlantshapecolorcolorpositionshapecolorheightroundyellowviolet-redaxial flowersinflatedgreentallOne form of trait (dominant) wrinkledgreenwhiteterminal flowerspinchedyellowshortA second formof trait (recessive) looked at single traits never counted the offspring of each type and thus failed to find ratios.)He continued each experiment through several pea generations.Mendel studied one trait at a time. For example, he crossed plants having white flowers with plants having violet-red flowers, but which were alike in all other traits. He found that all the first generation of offspring plants (symbolized as F1) had purple-red flowers, but neither plant had white flowers. By crossing tall and short plants, all offspring were tall. Mendel introduced the term dominant for the form of the trait that appeared in the first-generation offspring of its original cross; the trait that did not appear he called it recessive. Therefore, the reddish-violet flowers dominate over the white ones, and the large ones dominate over the short ones. For each of the seven pairs of either/or traits, Mendel found that one form of the trait was dominant and the other was recessive. The shapes of the features shown in the top row of Figure 2.1 are dominant; those in the bottom row are recessive. The properties were not mixed. Plants with red-purple flowers crossed with plants with white flowers produced offspring with red-purple flowers, not offspring with pink flowers. Tall plants crossed with short plants produced offspring the size of the tall parents, not half. Big F genotype and phenotype1The plants in Mendel's experiments were the same size as their large parents. They looked like his great parents; that is, the phenotype for size of it was large. But Mendel recognized that the hereditary endowment of the F1plants differed from their parents: the large parents were of an inbred line, so their total inheritance was large, but each F1The plant had large and small parents. Could this difference be visualized in heredity or genotype? Would it appear in future generations? Mendel discovered by studying the plants of the F1generation with itself (self-pollination) and creating a second generation, symbolized as F2🇧🇷 He got high plants and low plants in the F2, but not plants of medium height. When he counted them, he found that the tall plants outnumbered the short ones by about three times. Mendel performed similar experiments with other traits, such as flower color, and scored an F for each experiment.2Generation. She always found the same thing: in the F2generation, the dominant phenotype outperformed the recessive phenotype in a ratio of approximately 3:1, so that three-fourths of the F2The plants presented the dominant phenotype and one quarter the recessive one. Mendel's explanation of the inheritance of individual characters. Mendel proposed a multi-part hypothesis to explain his findings. Using modern terminology and some modern understanding, we can list the points covered by his hypothesis. The inheritance of traits is controlled by hereditary factors; Today these factors are called genes. Each individual has two copies of the gene for each trait. If each gene is represented by one letter, the genetic makeup (genotype) of an individual for a trait can be represented by two letters. Each gene exists in different forms; these variants of the same gene are called alleles. For example, the flower color gene in peas has one allele that produces purple-red flowers and another allele that produces white flowers. Dominant alleles will only produce the dominant phenotype, even if the recessive allele is present. Mendel designated the dominant and recessive alleles that control the same trait with a single letter of the alphabet, using an uppercase letter for the dominant allele and lowercase letters of the same letter for the recessive allele. For example, the V allele for purple-red flowers is dominant over the V allele for white flowers. (Currently, many genes are indicated by two-letter and three-letter combinations, and different alleles of the same gene by superscripts.) An individual whose genotype contains two identical alleles, such as VV or vv, is said to be homozygous for the trait. A person whose genotype combines different alleles, such as Vv, is called a heterozygote. Dominant alleles always appear in the phenotype, but recessive alleles are masked by their dominant counterparts. When both a dominant and a recessive allele for the same trait are present in a heterozygous individual, the dominant allele produces the phenotype. Recessive alleles produce the phenotype only when they are homozygous, in other words, when the corresponding dominant allele is absent. Genes behave like particles that stay apart instead of mixing. Recessive genes are turned on during F1Generation that has the dominant phenotype, but not because it belongs to an F heterozygote1individually. Yes the F1Individuals produce eggs and sperm, with the dominant and recessive alleles separate or "unconnected" from each other. Eggs and sperm are called gametes, with each gamete receiving only one allele of each gene after separation. The principle of separating alleles is often known as Mendel's first law. (The term "law" has been used more often in the past; in this case, it simply means a concept developed to explain the data.) During sexual reproduction, the gametes combine so that each F2The individual has two alleles, one from the egg and one from the sperm. This explains why the recessive phenotype in F1and why is it about a quarter of the F2Figure 2.3 shows Mendel's multipart hypothesis applied to one of the traits he studied. A pure line plant with purple-red flowers and VV genotype producing V gametes is crossed with a pure white flowering vv plant producing v gametes. All F1Plants that received V from one parent and v from the other have purple-red flowers and the heterozygous Vv genotype. half of the f1they carry the dominant V allele and the other half carry the recessive v allele, just like sperm, as indicated by the edges of the square in Figure 2.3. If the gametes of self-pollination F1are randomly combined to form the F2generation, one in four new individuals is homozygous for the dominant VV allele and has red-purple flowers, two in four are Vv heterozygous with red-purple flowers, and one in four is homozygous for the recessive vv allele and has flowers white flowers Figure 2.3 One of Mendel's experiments with peas that differ in only one trait. The ratio of purple-red to white phenotypes is therefore 3:1. A square like this, which shows how gametes combine to produce genotypes and phenotypes, is called a Punnett square. Independent variety. After studying the inheritance of individual traits, Mendel went on to study the inheritance of two traits together. In one of his experiments, the parents differed in both the shape and color of the seed. The parents of one group had round yellow seeds, were homozygous (YYRR) for both traits, and therefore all produced YR gametes. The other parents had wrinkled green seeds, were homozygous for both traits (yyrr), and therefore produced gametes of all years. The offspring of the first generation (F1) were all YyRr, heterozygous for both traits. All these F's1The plants produced seeds that were yellow (because yellow is dominant over green) and round (because round is dominant over purple-red).1SELF FERTILIZING white phenotype vv purple red genotype Vv wrinkled genotype). So far, no new principles have been involved. Mendel expected half of the F1contain the dominant allele Y and the rest contain the recessive allele y. He also expected that half of the gametes would contain the R allele and the other half would contain the r allele. But would it affect whether a gamete gets Y instead of y, whether it gets R or r? To find out, Mendel raised an F2Produced by self-pollination of some F1Plant. He obtained the 9:3:3:1½ Vviolet-red1/2 V ratio of the phenotypes shown in Figure 2.4, with 9/16 of the F2single-½ v SECOND GENERATION F2Eggs Sperm½ vpurple-red purple-red¼ VVwhite¼ Vv ¼ Vv¼ The vulva showed both dominant characters (both were yellow and round); while 3/16 were round but green; 3/16 were yellow but wrinkled; and only 1/16 had both recessive traits (green and wrinkled). Mendel later argued that this relationship could be explained if he assumed that all four possible gamete types (YR, Yr, yR, and yr) were produced in equal proportions, as shown by the borders of the square in Figure 2.4. This means that the inheritance of the seed color trait has no influence on the inheritance of the seed shape trait. This principle is called independent classification or Mendel's second law. All the features Mendel worked with were independently classified in this way, but as we'll see shortly, there are exceptions to Mendel's second law. Mendel's results, published in 1865, were ignored by most scientists. The reasons for the lack of impact of his theories are varied, but one contributing factor was that he presented his theories in the language of mathematics, to which most botanists of his generation were not. accustomed. Another factor was that Mendel's findings were published in an obscure journal that was not widely read. Later, in 1900, the other three scientists performed experiments similar to Mendel's, came to similar conclusions, and subsequently discovered Mendel's earlier work, GENERATION F1SELF-FERTILIATIONYellow, round Phenotype YyRr Genotype¼ YR1/4 AYyellow, roundEggs ¼ aR1/4 AAyellow, round1/16YYRR1/4 Year yellow, roundSperm¼ yR¼ AYyramyellow, round yellow, round1/16YyRR1/16YYRayel, round yellow, wrinkled1/16YyrYlowYrYry1, round yellow, round / 16YyRR¼ yr yellow, round1/16YyRryellow, wrinkled1/161/16YyRrgreen,green, round1/161/16YyRrgreen,yellow, wrinkled1/161/16YyRrGenotypes PhenotypePhenotypic ratioYyrrround1/16yyRryyRRgreen, wrinkled1/16yyrrround1/16yyRrYyrrYYRR, YyRR,YYRr, YyRr yyRR, yyRrYYrr , Yyrr yyrrayellow, round green, round yellow, wrinkled green, wrinkled 9/163/163/161/16 THOUGHTS Mendel's experiments distinguished between two alternative hypotheses: either traits mix so that offspring have traits intermediate between those of their parents , or the traits are inherited as discrete particles that do not mix. What hypotheses do Mendel's results support? Did you disprove a hypothesis? Did you test a hypothesis? A researcher pollinates tall pea flowers with pollen from short pea flowers. She collects and plants the seeds and all the plants that grow in the F1generation are as tall as the tall parent plants. the F1Plants produce flowers, each of which contains many sperm and many ovules. Each sperm and egg cell carries only one allele of each gene. What are the possible genotypes for plant height in F sperm?1Plant? What are the genotypes of the eggs? What fractions of gametes does each genotype have? The distribution of gamete types in the F1Are the plants the same or different when produced by cross-pollinating flowers from short pea plants with pollen from tall pea plants? To study two traits simultaneously, Mendel first crossed a plant strain bred for two traits (round and yellow) with another strain bred for different alleles of the same two genes. F1The flowers were self-pollinated and the F2Peas produced as before. When you have counted 16 from the F2Peas, how many would you expect to have the round, yellow, doubly dominant phenotype? When you counted 1600 F2Peas, how many round and yellow would you expect? Could your actual results differ from these expectations? Discuss the difference between the large and small sample sizes. Why are certain traits studied in some species and not in others? Why were peas a good choice for Mendel's experiments?The chromosome basis of heredity explains Mendel's hypotheses Figure 2.5 Structure of a nucleated cell. This particular cell comes from the tip of an onion root. nucleus cytoplasm Note that some of Mendel's assumptions raise questions that Mendel himself did not answer: Where are genes located? Why do genes exist in pairs? Why are different features classified independently of each other? What are genes? The answers to the first three of these questions were suggested by a young American scientist, Walter Sutton, who was reading about the rediscovery of Mendel's work in the 20th century. part, the cytoplasm (Figure 2.5; see Chapters 6, 10, and 12 for more information on cells). structure). Plants and animals can develop and grow because their cells divide. A cell divides into two cells. Scientists who have observed dividing cells through their microscopes have seen that the division of the cytoplasm is a very simple matter, but that the dividing nucleus undergoes a complex rearrangement of rod-shaped bodies called chromosomes. Chromosomes are not normally seen except when cells are dividing. When chromosomes are visible during cell division, differences in their structure can be seen. Each chromosome has a narrow constriction (the centromere) that divides it into two parts called the "long arm" and the "short arm." By measuring the length of these arms, we can differentiate the different chromosomes. The number of different chromosomes in a gamete is called the number of haploid chromosomes (N), with one of each type. All other cells in the body, called somatic cells, have twice as many chromosomes, called the diploid number of chromosomes (2N), with two of each size and shape (Figure 2.6). In diploid cells, each chromosome has a partner that corresponds to it in total length, length of long and short arms, and other characteristics. Any pair of chromosomes that look alike is called a homologous pair, and chromosomes from diploid cells characteristically occur in such pairs. The two chromosomes in a homologous pair are physically separate (not joined), but pair up during meiosis. Although they look the same under a microscope and carry the same genes, they often carry different alleles and therefore different genetic information. Gametes, which are haploid cells, have one chromosome from each homologous pair. Sutton noted that eggs in most species are many times larger than sperm because they have a greater amount of cytoplasm (see Figure 9.7, p. 298). The nuclei of the egg and sperm are about the same size, and these nuclei fuse during fertilization. From these facts, Sutton concluded that the genes are probably in the nucleus, not the cytoplasm, because the nucleus is divided carefully and precisely, whereas the cytoplasm is divided imprecisely. Even if genes were present in the cytoplasm, the greater amount of cytoplasm in the ovum would suggest that the ovum's contribution is always much greater than that of the sperm, in contrast to the observation that parental contributions to heredity are generally greater. they are the same No other structure is known to exist in cells, apart from chromosomes, separately in gametes and twice as many in somatic cells. The well-known arrangement and movement of chromosomes corresponds exactly to what Mendel postulated for genes. Genes must be on chromosomes. Mendel's genes are classified independently because they are on different chromosomes. However, there are only a limited number of chromosomes (4 pairs in fruit flies, 23 pairs in humans) but hundreds or thousands of genes. Sutton predicted that Mendel's law of independent classification would only apply to genes located on different chromosomes. Genes located on the same chromosome would be inherited together as a unit, a phenomenon now known as linkage. Sutton's idea that genes are located on chromosomes has been called the chromosome theory of heredity. To understand the chromosome theory of heredity and Sutton's prediction that some pairs of traits would not obey Mendel's law of independent classification, we must understand more about the movements of chromosomes in cells undergoing chromosome pair division. duplicates. cell division) a pair of homologous chromosomes, with each chromosome duplicated Mitosis In mitosis, a somatic cell divides in two, leaving each new cell with a diploid set of chromosomes, no more and no less. Therefore, each progeny cell that results from mitosis is genetically identical to the parent cell. The example used in Figure 2.6 shows a cell with two pairs of chromosomes, giving a total diploid count of four. Before cell division, the cell enters a stage called interphase. The cell enlarges and increases its cytoplasm. It also makes one copy of each of its chromosomes, so the cell has twice as many diploid chromosomes (eight chromosomes in our example). The relationship between duplicated chromosomes and homologous chromosomes is shown in Figure 2.7. As shown in Figure 2.8, no chromosomes are seen in the cell nucleus during interphase. Mitosis then goes through four stages: prophase, metaphase, anaphase, and telophase, as shown in Figure 2.8. With the onset of prophase, the chromosomes shorten and thicken and become visible under the microscope. Each chromosome is now attached to its new duplicate created during interphase. At the end of prophase, the membrane surrounding the nucleus ruptures. During metaphase, each chromosome attached to its duplicate lines up along the center of the cell. The other chromosome of each type also attaches to its newly synthesized duplicate and also goes to the midline of the cell. Homologous chromosomes are not in contact with each other, but are randomly distributed along the midline, each attached to its duplicate. In anaphase, each chromosome separates from its attached duplicate, and the chromosome and its duplicate begin to move toward opposite ends of the cell. The other chromosome of each type does the same, separating from its attached duplicate, and this homologous chromosome also moves from its duplicate to the opposite end of the cell. In telophase, the chromosomes complete their movement toward each end of the elongated cell. Since each chromosome and its duplicate (made at interphase) have been moved to opposite ends of the cell, each end of the cell now has the diploid number of chromosomes, consisting of two chromosomes from each homologous pair. At the end of telophase, a nuclear membrane reappears around each diploid set of chromosomes, forming two nuclei, one at each end of the cell, and completing mitosis. After mitosis is complete, the cytoplasm divides between the two nuclei, completing the division of one diploid cell into two diploid cells. In all sexually reproducing species, two haploid gametes combine to form a diploid cell called a zygote, which can develop into a new individual organism. Gametes are produced in specialized cells in a process called meiosis. Meiosis proceeds in a similar way to mitosis, but with the addition of a second round of cell division. This leads to a different end result than in mitosis: four cells are produced in meiosis, each with a haploid number of chromosomes. As in mitosis, each duplicated chromosome thickens and becomes visible; then the nuclear membrane collapses and the chromosomes align along the midline of the cell. However, this step is very different from the mitotic process. In mitosis, the homologous pairs of chromosomes arrive separately at the midline. In the first division of meiosis, as shown in Figure 2.9, the two homologous chromosomes, each with its attached duplicate, come together in the midline as quadruplets. From each homologous pair, one chromosome (with its attached duplicate) goes to each end of the cell. Nuclear membranes form and the cell separates into two descendant cells, completing the first INTERMEDIATE PHASE. The cell increases in size and each chromosome is duplicated, although at this stage they are not visible in the nucleus. The cell now has double the diploid number. Nuclear membrane chromosomes attached to their duplicated nuclear membrane fragments PROPHASE Duplicated chromosomes thicken and shorten and become visible under the microscope as conjoined pairs. The membrane surrounding the nucleus ruptures near the end of prophase. METAPHASE Each chromosome and its attached duplicate align along the midline of the cell. Chromosomes separate from duplicates Diploid chromosome set Cytoplasmic division Reconstruction of nuclear envelope The chromosome and its duplicate move to opposite ends of the cell. Telophase A complete diploid set of chromosomes arrives at each end of the cell, a nuclear membrane reassembles around each set to form two nuclei, and the cytoplasm begins to divide in two. Figure 2.9 Meiosis. A cell with a diploid number of chromosomes (2N = 4 in this example) divides twice to produce four haploid gametes (here with two chromosomes each). diploid progenitor cell, meiotic division. At this stage of meiosis, each new cell contains one chromosome from each homologous pair, and each chromosome remains attached to its newly synthesized duplicate at the beginning of meiosis. Each chromosome and its duplicate come from a single member of a homologous pair. Instead, at the end of mitosis, each cell has a copy of both chromosomes from each homologous pair. The first meiotic division is followed by a second division in each of the two new cells. The nuclear membranes collapse again, and each chromosome now separates from its attached duplicate. Nuclear membranes form and cells divide. The end result is four cells. Since no further chromosome replication has occurred between the first and second meiotic divisions, in each of the FIRST MEIOTIC DIVISION and the SECOND MEIOTIC DIVISION, chromosome duplication, thickening, and collapse of the homologous chromosome pairs occur. the nuclear membrane, and its duplicates are grouped together. and if they align along the midline separate the pairs by itself, each chromosome remains attached to its duplicates; nuclear membranes reassemble; cell divisions; Chromosomes line up along the midline, each chromosome separates from its duplicates, nuclear membranes reassemble, cells divide, four haploid gametes, four new cells or gametes, and you end up with the haploid number of chromosomes. Meiosis, therefore, has three main differences from mitosis: (1) it has an extra round of cell division; (2) the end result is four cells, each containing a haploid number of chromosomes; (3) During metaphase, homologous chromosomes align and form midline quadruplets. This last difference allows the additional characteristic of crossover to occur. A chromosome from each linked pair can exchange part of itself with the corresponding part of the linked homologous pair, as indicated by the interchange of red and blue segments in Figure 2.9. This phenomenon allowed the discovery of gene connection, which will be discussed below. sexual life cycles. Once haploid gametes are produced, they can unite through sexual reproduction and form a diploid zygote, a process studied by the Austrian zoologist Theodor Boveri and the American zoologist Ernest E. Just (see Figure 1.4). Figure 2.10 shows a sexual life cycle. The gametes fuse into a zygote; then, in most species, the zygote undergoes repeated mitosis to become a multicellular adult. Each somatic cell contains the complete set of diploid chromosomes, and therefore all somatic cells are genetically identical. As the organism develops, different somatic cells become specialized for different functions (see Chapter 12), although they all retain the full set of diploid chromosomes. Some of these cells specialize to undergo meiosis, producing new haploid gametes and completing the sexual life cycle. Most, but not all, multicellular organisms have a sexual life cycle that alternates between haploid germ cells and diploid somatic cells. Other researchers were quick to confirm his prediction. A British geneticist, William Bateson, described linked genes in a cross between pea varieties. Other researchers soon discovered similar examples in fruit flies (Drosophila), corn (Zea mays) and other species, showing that Mendel's laws and Sutton's theory are not exclusive to peas or plants. Figure 2.11 shows a cross showing that two genes in maize are linked. Plants of the CCSS genotype (colorful and full seeds) crossed with ccss plants (colorless and shrunken seeds) all produced seeds of the colored and full phenotype among the F1🇧🇷 In this experiment, F1Plants (heterozygous CCSs) did not self-pollinate as in Mendel's experiments as in Figures 2.3 and 2.4. instead of the f1Heterozygous plants of the double recessive ccss genotype were fertilized. This type of cross where an F1crossed with one of the main types is called a backcross. In the backcross progeny, most of the colored seeds were also full, and most of the colorless seeds also had the wilted phenotype. The genes for these two traits are thought to be related. The fact that they are linked and not classified independently can be explained by assuming that the genes for the two traits are on the same chromosome. Figure 2.10 Cycles of sexual life. In sexual reproduction, haploid gametes are united by fertilization to form a new diploid individual, one from each pair of homologous chromosomes from each parent. In multicellular organisms, the diploid zygote divides by mitosis to form the adult organism. Each somatic (body) cell contains a set of chromosomes similar to those of the zygote. In a male organism, meiosis produces sperm as shown. In a female organism, meiosis produces ovules specialization cell divisions diploid haploid FERTILIZATION DEVELOPMENT PRODUCTION OF GAMETES LIFE CYCLE Figure 2.11 A cross between inbred maize plants with different alleles for two linked genes. However, also note in Figure 2.11 that a small number of the backcross progeny were not of the colored and whole or colorless and wilted seeds, but had colored and wilted or colorless and complete seeds. These outliers had novel (non-parental) combinations of phenotypes for the traits; It was concluded that the underlying recombinant genotypes arose from the process of crossing over, in which chromosomes break and recombine by exchanging pieces. Some microscopists thought they saw X-shaped arrangements of chromosomes during meiosis (see Figure 2.11) that looked like crossing over, but many scientists weren't sure. Confirmation of the chromosome theory Sutton's theory that genes are located on chromosomes had to wait three decades to be confirmed by other geneticists. In 1931, Harriet Creighton and Barbara McClintock confirmed the chromosome theory of heredity in maize; Later that year, Curt Stern observed the same thing in fruit flies. Creighton and McClintock used plants whose chromosomes had structural abnormalities at both ends, which allowed them to see the chromosomes under a microscope. What they were able to show was that genetic recombination (the rearrangement of genes) was always accompanied by crossing over (the rearrangement of chromosomes). McClintock discovered genes that move from locus to locus, so-called color transposables, complete colorless phenotypes, shrunken phenotypic elements, or jumping genes, a discovery for which he later received the Nobel Prize for roughly a measure of the distance between them along the length of the gene. of the chromosome. Recombination between closely related genes (genes that are close together) is a rare event, while recombination between more distant genes is more common. Crosses between individuals that interbreed during gamete formation have allowed geneticists to determine the linear arrangement of many genes and their approximate distribution.sDistances between genes on the chromosomes of many species. An interesting footnote to Mendel's work was published in 1936 by the British geneticist R.A. Fisher, who noticed that peas have seven pairs of chromosomes. numeric, full4032colorless, shrunken4035colorful, shrunken149colorless, full152 Mendel selected seven features, which were classified independently because each is on a different chromosome. of each phenotype parental types 96.4% non-parental types 3.6% Because the probability of this occurring by chance is extremely small, Fisher concluded that Mendel may be looking at many more traits and only the results of the seven classified traits independently whose heredity he managed to understand (see Figure 2.1). In a cross between pea plants of the genotype YYRR (round yellow seeds) and yyrr (rough green seeds), the F1The plants are all YyRr. Make a series of large drawings showing the movements during mitosis of the chromosomes that carry these genes in the cells of an F1heterozygous plant. for the same F1The heterozygous (YyRr) plants described in question 1 provide a series of drawings showing how chromosomes separate in the first division of meiosis and the second division of meiosis. Label each diagram with the symbols Y, y, R, and r to show how the four types of gametes are formed. Would you expect the cross YYRR ¥ yyrr to give the same results as YYrr ¥ yyRR? Why or why not? Genes on the sex chromosomes determine sex and sex-linked characteristics Not long after Sutton suggested that chromosomes carry genes, chromosomes and their abnormalities were studied in fruit flies and humans. Much has been learned about human genetics through the study of chromosomes. In particular, some unusual conditions are associated with changes in the chromosomes. During mitosis and meiosis, double-stranded DNA continues to wrap around scaffold proteins and then around itself until the structure becomes thick enough to be visible under a light microscope. This structure is generally what we think of as a chromosome. During mitosis, when the chromosomes are visible, the cells can be squeezed onto a glass slide. Pictures of the chromosomes can be taken through a microscope, and the pictures can then be sectioned. Using the chromosome lengths and banding patterns, geneticists can align the images and locate the homologous chromosomes in Figure 2.12 Human male and female karyotypes. couples together. Such an arrangement is called a karyotype. The karyotypes of a female and a male are shown in Figure 2.12. The chromosomes of nearly all humans can be arranged in a karyotype similar to that shown in Figure 2.12, with 1 2 3 4 56 7 8 9 10 11 1213 14 15 16 17 1819 20 21 22 XY the XX (female) karyotype. ) 1 2 3 4 56 7 8 9 10 11 1213 14 15 16 17 1819 20 21 22 X Yder XY karyotype (male) TDF, testis determining factor.SRYProteinProgesterone TDF Testosterone46 chromosomes arranged in 23 pairs. Of the 23 pairs of chromosomes, 22 pairs are the same in both sexes (the autosomal chromosomes). The two chromosomes in each of these pairs are homologous, meaning they carry the same set of genes (although possibly two different alleles of a gene). day 23third pair of chromosomes (labeled X and Y in Figure 2.12) are called the sex chromosomes because they differ in males and females and have a role in determining a person’s sex. The X and Y chromosomes are only partly homologous: they do pair during meiosis, but only some of their genes are present on both the X and Y chromosomes.Sex determinationHuman females typically have two similar sex chromosomes, symbolized as XX. Human males typically have one X chromosome and one different sex chromosome, the Y chromosome, and thus are symbolized as XY (see Figure 2.12).Not all human females are XX and not all human males are XY. There are unusual situations in which a cross-over during meiosis between an X and a Y chromosome is followed by an exchange of chromosome pieces. Approximately 1 in 20,000 normal males is chromosomally XX, but one of his X chromosomes contains a small piece of the Y chromosome. About the same frequency of normal females are chromosomally XY but are missing the same small piece of Y chromosome. One such XY female had 99.8% of the Y chromosome, indicating that a maledetermining factor, or testis-determining factor, was located in the 0.2% portion of the Y chromosome that she did not have. Examination of this 0.2% portion of the Y chromosome led to the identification of a gene now called SRY, hypothesized to induce development as a male.The SRY gene helps determine sex by producing a protein, the SRY protein, that allows the production of another protein, the testis-determining factor, that converts progesterone into testosterone (Figure 2.13). Both progesterone and testosterone are hormones, small molecules by means of which cells communicate with one another. Testosterone acts on cells to induce the development of male organs in embryos. If progesterone is not converted to testosterone, it is instead converted to estrogen, which triggers the development of female organs. Embryos with an SRY gene thus become males, and embryos without an SRY gene become females. However, there are also case of SRY-negative individuals who are phenotypically male, demonstrating that other genes in addition to SRY are involved in sex determination.Sex-linked traitsVery few genes are, like SRY, located on the Y chromosome. Many more genes are located on the X chromosome. Genes that are on the X chromosome and not on the Y chromosome are said to be sex-linked. Females can be either homozygous or heterozygous for sex-linked traits because they have two X chromosomes and therefore two alleles of every sex-linked gene. If the allele for a trait is recessive then a heterozygous woman has the dominant phenotype but is said to be a carrier of the trait. Because a male has only a single X chromosome, he has only a single allele for each sex-linked trait, and this allele determines his phenotype for that trait. The inheritance of a recessive sex-linked trait,red–green colorblindness, is shown in Figure 2.14. If a woman is heterozygous for this trait, she shows the dominant phenotype and is not colorblind. However, a male who carries the recessive allele for colorblindness on his X chromosome will be colorblind. Note that a single sexlinked allele is phenotypically displayed in a male regardless of whether it is dominant or recessive.Females generally possess two X chromosomes, but in a given cell only one of them has active genes that make a product or expressFigure 2.14Inheritance of red–green colorblindness, a sex-linked recessive trait. a phenotype. Females thus express one phenotype (from their mother’s X chromosome) in some cells and another phenotype (from their father’s X chromosome) in other cells. This expression of two phenotypes at the cellular level is called mosaicism. All females who are heterozygous are mosaics for X-linked genes. For example, in a female heterozygous for an X-linked allele for colorblindness, patches of cells within the retina of the eye (see Chapter 13, p. 478)cannot respond to color. Other patches of cells, which express thechromosomes in spermnormal father XYYcarrier mother XXXXYchromosomes in eggs normal allele on the other X chromosome, respond normally.Chromosomal variationMost humans have 46 chromosomes, consisting of a pair of sex chromosomes and 22 other pairs of chromosomes. Other chromosomal patterns have multiple consequences, called syndromes, usually named after the physicians who identified them. Several such variations of the sex chromosome number are known. For example, theXcarrier daughteraffected sonXXnormal daughterXXYnormal sonXXXXY chromosomal type (Figure 2.15A) results in Klinefelter syndrome; persons with this condition have male phenotypes but are sterile. Some of the symptoms of Klinefelter syndrome can be= female = maleratio among offspring 1 normal : 1 carrier : 1 normal: 1 affected successfully treated with hormones. In contrast, Turner syndrome results from the XO chromosomal type, in which only one X chromosome is present, the O representing its missing partner (Figure 2.15B). Persons with Turner syndrome develop as females; however, their ovaries do not produce female hormones. Puberty does not take place and gametes do not develop, resulting in infertility. The infertility cannot be overcome at present, but the other symptoms of Turner syndrome can now be treated hormonally with much success.Turner and Klinefelter syndromes are believed to result from the same cause, an abnormal meiosis of the sex chromosomes. In the abnormal meiotic divi-sion, the two sex chromosomes fail to separate, resulting in some egg cells’ having two of the mother’s X chromosomes and some having none. Abnormal separation of chromosomes during gamete production has in fact been observed, partly confirming the hypothesized series of eventsnormal phenotypeFigure 2.15Two variations in human X and Y karyotypes. shown in Figure 2.16.Klinefelter syndrome (XXY)Turner syndrome (XO)Figure 2.16Abnormal meiosis during egg production, showing how certain chromosomal variations may arise.normal premeioticAlso supporting the hypothesis is the very rare XXX chromosomal abnormality; most XXX females are mentally retarded and sterile. The Y- only type of embryo, also predicted by the hypothesis, has never been observed, presumably because it dies at a very early stage of development. Abnormal chromosome separation can also take place during the formation of sperm cells, resulting in XY sperm and O sperm. When these fertilize a normal X egg, again either Klinefelter syndrome (XXY) or Turner syndrome (XO) can result.There are also variations in number for chromosomes other than the sex chromosomes. The most common of these is associated with Down syndrome, marked by facial characteristics (including an epicanthic foldover the eyes), heart abnormalities, and a variable amount of cells, each with two X chromosomesand 22 pairs of other chromosomes (not shown)meiosisX X22 pairs of other chromosomesX Xnormal meiosis (X chromosomes separate)Xabnormal meiosis (nondisjunction) (X chromosomes do not separate)mental retardation. Down syndrome usually results from an extra chromosome 21 (Figure 2.17). Other chromosome abnormalities are less common. For example, Patau syndrome (three copies of chromosome 13) results in severe mental retardation, a small head, extra fingers and toes, and usually death by one year of age. In addition to extra chromosomes, part or all of a chromosome can be missing. The cri du chat syndrome is caused by deletion of the short arm of chromosome 5 and results in a small head, a catlike cry, and mental retardation.In addition to these changes in chromosome number, there are several kinds of large-scale changes involving chromosome fragments. Chromosome fragnormal eggegg with twoegg with noments may become duplicatedXXfertilization with X-bearing spermX chromosomes X chromosome(repeated); they may become attached at a new location, possibly on a different chromosome; or they may be lost entirely. A chromosome fragment may also be turned endorfertilization with Y-bearing spermresults in normal(XX) femaleYXresults in normal (XY) maleresults inXXX femaleresults in Klinefelter syndrome (XXY)results inTurner syndrome (XO)embryo diesto-end and reinserted at its former location. Of these four types of chromosomal changes, end-to-end inversions are the most frequent, and have the most limited effects, while the other three types may result in nonviable phenotypes when the rearranged fragments of DNA are long.Social and ethical issues regarding sex determinationAs we have seen, the determination of a person’s sex is not always unambiguous. There is a strong societal expectation that each person should be categorized as either male or female, yet 17 out of 1000 people cannot be so clearly categorized. Some are people with XY chromosomes but female anatomy or XX chromosomes but male anatomy. Some people have partly male and partly female anatomy.Realization that there are XX males and XY females forced the International Olympic Committee to reexamine the stipulation that only XX individuals could compete in female sporting events. If chromosome appearance is not sufficient to determine which individuals are male, should the presence of the SRY gene or the hormone testosterone be used as the test? Either turns out to be problematical. Females also have testosterone, although generally in smaller amounts than males. Also, there are rare XY individuals who have the functional SRY gene and produce male concentrations of testosterone but are nevertheless phenotypically female because they lack a functional allele of a different gene, the gene for a protein that allows cells to respond to testosterone. Cells cannot respond to a hormone during development or during adult life unless they possess receptor molecules to bind that hormone. The International Olympic Committee now uses the presence or absence of the functional SRY gene to decide the sex of Olympic athletes, but clearly sex is not determined by one single gene. Other genes, including genes such as the testosterone receptor gene on chromosomes other than the sex chromosomes also have a role in sexual development. Thus, even though we refer to X and Y as the sex chromosomes, many genes on many other chromosomes are also involved.Clearly male and female are not either/or categories. There are persons who fall between, either because of chromosomal variation or variation in alleles at particular genes such as SRY or the testosterone-receptor gene. All of these different variations are called intersex. In many cases, babies born with ambiguous genitals have been treated, either withFigure 2.17Down syndrome.The karyotype with an extra chromosome 21 associated with most cases of Down syndromeA child with Down syndromeTHOUGHT QUESTIONShormones or surgically, to make them conform to one sex or the other. Sometimes this has been done without the informed consent of the parents, raising further ethical issues.People with variations in the relation between their karyotype and their phenotype are not defective individuals; they just do not fit a previously held view of what determines the sex of an individual. More recently, the research of Anne Fausto-Sterling and others has been calling into question the practice of assigning everyone to one of two categories of male or female. Why should categories that are essentially social constructions (derived by society) be placed over the much greater range of variation that exists in biological reality?Sports officials have repeatedly asked female athletes to submit to testing to confirm their femaleness, but comparable proof is seldom demanded of males. Why do you think this disparity exists? Can you think of other ways besides sex in which athletes might be classified? Could we use age as a criterion? Could we use fat-tomuscle ratios?Individuals with Klinefelter syndrome or Turner syndrome are fully functional aside from their infertility, yet many are ‘treated’ with hormones to give them a less indeterminate appearance of secondary sexual characteristics such as breasts. Whydo humans tend to think of such differences as ‘abnormalities’ needing ‘treatment’ rather than as normal variation within a trait?Should the sexual phenotype include more than two categories, categories other than male and female? If it did, would a person who was intersex want to reveal that on any of the many forms where we are asked to declare which sex we are? Why or why not?Are biological categories neutral and objective? That is, can they be free of the values placed on them by society?The Molecular Basis of Inheritance Further Explains Mendel’s HypothesesWe now address the last of the four questions posed earlier. What are genes made of? In other words, what chemical substance transfers genotypes from parents to offspring?The story begins with a curious experiment carried out in 1928 by Frederick Griffith, a U.S. Army medical officer attempting to develop a vaccine against pneumonia. Griffith worked with two strains of bacteria that differed in their outer coats. Strain S had an outer coat that gave a smooth appearance when masses of bacteria (called colonies) were grown on agar in dishes. The smooth-colony bacteria were virulent, which means that the bacteria cause a disease (pneumonia in this case). Strain R of the same bacterial species lacked the outer coat, which gave the colonies of this strain a rough appearance, and they were nonvirulent. (S stands for ‘smooth,’ R for ‘rough.’) When strain S was injected into mice, all the mice died of pneumonia. Strain R, when injected, didnot kill mice, nor did bacteria of strain S that had been killed by heat. The surprising result, shown in Figure 2.18, was that a mixture of live bacteria of strain R and heat-killed bacteria of strain S did kill mice. Furthermore, living S bacteria were isolated from all mice that died this way. Griffith interpreted this experiment as showing that something in the dead S bacteria had somehow transformed the living R bacteria into virulent S bacteria, and this type of change came to be known as transformation. The bacteria had been altered genetically, not justFigure 2.18Griffith’s experiment demonstrating hereditary transformation in bacteria.smooth coloniesvirulent strain-S bacterialiveinjected into micemice die of bacterial infectionsmooth coloniesvirulent strain-Sbacteria heat killedinjected into mice mice remain healthyrough coloniesnonvirulent strain-R bacterialiveinjected into micemice remain healthysmooth coloniesvirulent strain-S bacteriaheat killedliving bacteria of strain S isolated from bloodrough coloniesnonvirulent strain-R bacterialiveinjected into mice mice die of bacterial infection phenotypically. A change that was only phenotypic would not be passed on to future generations, but Griffith demonstrated that descendents of the transformed bacteria were also of strain S and continued to kill mice. What Griffith had done in his experiment was transfer a genetic trait from one bacterial strain to another. What was the chemical substance that had been transferred? Griffith’s use of bacteria as an experimental species and the unequivocal evidence that genetic material had been transferred in his experiment is significant because it was the background for work two decades later that demonstrated what the chemical substance is. This section describes the research that revealed the chemical substance of the gene, the composition of this substance, and how it is replicated. We also learn how the chemical substance directs the synthesis of proteins and how changes in the substance can produce changesin proteins.DNA and genetic transformationFrom the beginning of the twentieth century into the 1940s, most researchers thought that proteins were the most likely candidates to be the chemical substance of genes. They thought this because proteins were known to be complex and varied, while most other molecules were thought not to be. In an attempt to discover whether protein was indeed the chemical substance, three bacteriologists, Oswald Avery, Colin MacLeod, and Maclyn McCarty, in 1944 conducted a chemical study of the bacteria that Griffith had injected into his experimental mice. First, they were able to show that a chemical extract of heat-killed S bacteria transformed strain R into strain S. They then separated the strain-S extract into different fractions, each containing different types of chemical molecules. They found that the fraction containing the nucleic acids transformed strain R into strain S, but that the protein fraction did not.Finally, they distinguished between the two major types of nucleic acids (DNA and RNA) by using enzymes. Enzymes are biological molecules (nearly always proteins) capable of speeding up chemical reactions without themselves getting used up in those reactions. Enzymes control many biological processes, and the action of most enzymes is very restricted in that specific enzymes act on specific types of molecules. The enzyme deoxyribonuclease (DNase) specifically breaks down DNA. DNase treatment destroyed the ability of the strain-S extract to transform the strain-R bacteria, demonstrating that the chemical that carries the genetic material is, in fact, deoxyribonucleic acid (DNA). On the other hand, the enzyme ribonuclease, which breaks down RNA, had no effect on the ability to transform; ribonucleic acid (RNA) is therefore not the genetic material.The discovery of Avery and his co-workers did not get the attention it deserved. Doubters still remained. It took about a decade for many scientists to accept that DNA is the genetic material. Experimental work on the problem had meanwhile shifted from using bacteria to using viruses. In 1952, two American virologists, Alfred Hershey and Martha Chase, published the results of a landmark experiment that confirmed the finding that DNA, not protein, is the genetic material. For their experiment, Hershey and Chase used a virus that infects bacteria and reproduces within them. They infected bacteria with the viruses and studied the viral offspring. It was known that this virus consisted only of protein andDNA. Was it the protein or the DNA that carries the genetic material?In preparation for their experiment, Hershey and Chase grew some viruses in a medium containing radioactive phosphorus (32P) and others in a medium containing radioactive sulfur (35S), atoms that the virus needs to make new viruses. Because DNA contains phosphorus but protein does not, the new viruses grown with 32P had radioactive phosphorus in their DNA but no radioactivity in their protein. In contrast, the proteins, but not the DNA, of viruses grown with 35S were radioactive because proteins contain sulfur but DNA does not. Because radioactivity is easily detected, material prepared in this way is said to be radioactively labeled. Hershey and Chase applied the radioactive labels so they would be able to ‘see’ what happened to the viral DNA and protein when the viruses infected bacteria.Hershey and Chase exposed Escherichia coli bacteria to the radioactively labeled viruses for long enough to permit the viruses to infect the bacteria. Part of the virus enters the cells that they infect and directs the replication of more viruses, producing thousands of new virus particles and eventually killing the bacteria and breaking them open to release the viruses (Figure 2.19A). Was the injected material that was carrying theFigure 2.19The Hershey–Chase experiment. This experiment confirmed DNA as the genetic material.Pattern of viral infection of E. coli bacteria.capsule remains outside virusesvirus injects genetic materialbacterial celllatervirus genetic material directs replication of new virus; many new virus particles releasedViruses grown with radioactive sulfur.bacteria not radioactive agitate in blenderseparate bacteria from surrounding liquid in centrifugeliquid contains radioactive virus proteins©Viruses grown with radioactive phosphorus.bacteria radioactive from radioactive viral DNA agitate in blenderseparate in centrifugevery little radioactivity in surrounding liquid (from viruses that did not infect the bacteria) viral genotype DNA or protein? Hershey and Chase devised a way to interrupt the viral cycle after the infection period by using a kitchen blender to knock the attached virus capsules off the bacterial surfaces. These detached capsules could easily be separated from the bacteria by spinning the mixture in a centrifuge. Viral material that had been injected into the bacteria continued the process of viral reproduction, eventually rupturing and killing the bacteria. When 35S-labeled viruses were used, the radioactive proteins remained outside the bacteria (Figure 2.19B); the viruses eventually released were not radioactive so they had not used radioactive protein to replicate themselves. However, when the 32P-labeled viruses were used, the radioactive DNA entered the bacteria, making the bacteria radioactive. The viral offspring released when these bacteria broke open were also radioactive (Figure 2.19C), showing that they had used some of the radioactive DNA in their reproduction.This experiment upheld the hypothesis that the genetic material of the virus was DNA. It falsified the hypothesis that the viral genetic material was made of protein. DNA had been identified as the genetic material, but its composition and structure were still a mystery.The structure of DNAChemical breakdown of DNA into its parts showed that it was made of phosphate groups, deoxyribose (a sugar), and four nitrogen-containing bases called adenine (A), guanine (G), thymine (T), and cytosine (C) (Figure 2.20A). Biochemists soon realized that the deoxyribose could form a middle link between the phosphate groups and the nitrogenous bases, creating units called nucleotides (Figure 2.20B). Beyond this, the structure of DNA was unclear, and it was not at all obvious how the structure could give DNA the ability to carry genetic information.Chargaff’s rules. Some researchers suggested that the order of bases in DNA repeated regularly: AGTCAGTCAGTC…. If this were true, then the amounts of the four nitrogenous bases should be equal: there should be 25% of each of the bases in a DNA molecule. To test this hypothesis, biochemist Erwin Chargaff of Columbia University took DNA from various sources, broke it down using enzymes, and measured the relative amounts of the four nitrogenous bases. His findings were as follows.The proportions of the four nitrogenous bases are constant for all cell types within a species. For example, all human cells contain about 31% adenine (A), 19% guanine (G), 31% thymine (T), and 19% cytosine (C), regardless of whether the DNA is from brain cells, liver cells, kidney cells, or skin cells.Although the proportions are constant within a species, they differ from one species to another. All humans, for example, have the same proportions of the four bases. Proportions are different in rats and in bread molds, but all rats have the same proportions as one another and so do all bread molds.The most unexpected finding, and the hardest to explain, was that the proportion of adenine was always the same as the proportion of thymine (within the limits of experimental error), and the levels of cytosine and guanine were also equal. These findings (symbolized as A = T and G = C) became known as Chargaff’s rules.The three-dimensional structure of DNA. In 1953 James Watson and Francis Crick, two geneticists working in Cambridge, England, proposed a structure for DNA that explains Chargaff’s rules and also explains how DNA carries genetic information. They did this with the help of some X- ray diffraction information obtained from the Cambridge laboratory of biochemist Maurice H.F. Wilkins, with whom they later shared a Nobel Prize. The data from Wilkins’s laboratory were gathered and interpreted by Rosalind Franklin, a biochemist, whose contribution never received the recognition it deserved (see our Web site, under Resources: Franklin). The X-ray diffraction information suggested certain dimensions and distances for the repetition of structures within the DNA molecule. From this information, Watson and Crick constructed the model of DNA struc-ture summarized in the following list:Each phosphate in a DNA molecule is attached to a deoxyribose sugar, which in turn is attached to a nitrogenous base. The three parts together constitute a nucleotide (see Figure 2.20B).The phosphate group of one nucleotide is also connected to the deoxyribose sugar of the next nucleotide. The alternation of phosphates and sugar units thus forms a backbone that holds the nucleotides together in a strand, with the nitrogenous bases pointing inward (Figure 2.21A).Each strand is a linear sequence of bases (it does not branch) that, because of the angles of the chemical bonds, is twisted in the shape of a corkscrew (a helix).Figure 2.21The three-dimensional structure of DNA.Thousands of nucleotides are strung together by a sugar-phosphate backbone.portion of DNA strandTwo strands of DNA twist around one another to form a double helix. A straightened portion of this double helix resembles a ladder with the paired (complementary) bases forming the rungs.paired bases©Two nucleotide sequences running in opposite directions pair with one another, with each adenine (A) pairing with a thymine (T), and each guanine (G) pairingwith a cytosine ©.PD A T D sugarphosphate backbonesP complementary bases PG C DDP PT A DDP PA T DDP P backboneA T DDP hydrogen bonds PD C G D PFigure 2.22DNA replication. The two strands run in opposite directions, as denoted by the arrowheads on the orange (old) backbones. The direction of synthesis is indicated by the arrowheads on the red (new) backbones. Note that either strand contains all the information needed to synthesize the other (complementary) strand.DNA has two strands wound around each other, forming a double helix, with the bases arranged in the interior, like steps in a spiral staircase (Figure 2.21B).The strands run in opposite directions and are so arranged that an adenine on one strand is always paired with a thymine on the other strand, and vice versa. Also, cytosine on one strand is always paired with guanine on the other strand, and vice versa (Figure 2.21C). These pairings of matching (complementary) bases explain Chargaff’s rules.C and G fit together and T and A fit together because their shapes are complementary (see Figure 2.20). Because of these base pairings, each strand contains all the information necessary to determine the structure of the complementary DNA strand.DNA replicationWatson and Crick’s model for the structure of DNA led quickly to an understanding of the mechanism of replication, the process by which the cell makes copies of the DNA molecules. Before DNA replication, the two strands of the double helix unwind and separate from each other, as shown in Figure 2.22A. Notice the orientation of the 5-sided deoxyribose molecules in the orange-colored backbone, which shows that the two(A) UNWINDINGThe two strands of the DNA double helix separate.© JOININGEach new row of bases is linked into a continuous strand by joining adjacent sugars and phosphates. Each double helix contains one new strand and one original strand. original strands remain unchanged new strands formedA T A TA TC G C GC GT A T AT A G C G C G C(B) PAIRINGoriginal DNA(D) THE REPLICATION FORKearly step later stepNew nucleotides pair with their complementary nucleotides exposed on each strand.TA TC G GT AG CCoriginal DNA strandsenzymenewly made strandsreplication fork movesstrand synthesized continuously toward the forkstrand made by discontinuous synthesis: fragments synthesized away from the fork and then joined togetherstrands run in opposite directions. After separating, the strands are bound by an enzyme (DNA polymerase), which actually begins the replication process. New strands of DNA are synthesized one nucleotide at a time, with one of the existing strands serving as a template (pattern to be copied). If the next unmatched base on the template is adenine (A), then a thymine (T) nucleotide (adenine’s complementary base) is added to the growing new strand opposite the adenine. In like manner, G is added opposite C, C opposite G, and A opposite T (Figure 2.22B). The other existing strand is simultaneously acting as a second template and other complementary bases pair with it. The backbone of the new strand is formed by joining (bonding) the phosphate group of the incoming nucleotide to the deoxyribose sugar of the previous nucleotide (Figure 2.22C).Recall that the two originally existing DNA strands run in opposite directions. Consequently, synthesis on the two template strands proceeds in opposite directions. One new strand of DNA is thus synthesized continuously, with the direction of synthesis running towards the replication fork, the place where the two original strands are coming apart. The other strand, however, is synthesized in the opposite direction, away from the replication fork. This strand must be synthesized in short fragments that are later joined together (Figure 2.22D).THOUGHT QUESTIONSBefore either mitosis or meiosis, the DNA in each chromosome is replicated, forming two identical chromosomes that are attached as a pair at the beginning of mitosis or meiosis. Does one of these contain the old DNA and the other the newly replicated DNA? Or does each contain some of the old DNA and some of the newly replicated DNA?Is the DNA sequence in the two chromosomes of an attached pair identical? Is the DNA sequence in the two chromosomes of a homologous pair identical?DNA is a double helix, two complementary strands that wind around each other. A particular gene is on one of the two strands. A different gene at a different location may be on the same strand or on the other strand. In transcription, the strand with the gene acts as a template for mRNA synthesis. What happens on the other strand during transcription? What happens on the other strand during DNA replication?Concluding RemarksIn this chapter we have seen how scientists, beginning with Mendel, used observation and experimentation to understand the patterns of inheritance of simple, either/or traits. The same rules that work for pea plants work for other species, including humans. The units that assort and segregate in inheritance have come to be known as genes. Genes are located on chromosomes, a hypothesis that was first suggested because the numbers, locations, and movements of chromosomes could explain theobserved patterns of inheritance. Genes were later found to be composed of DNA, a molecule that consists of long chains of nucleotides. The double-stranded structure of DNA accounts for its ability to be replicated accurately. These landmark discoveries are summarized on our Web site, under Resources: Landmarks in genetics. Scientists now realize that no gene works independently of its cellular environment and that phenotypes for most traits are modifiable. Many traits in many species follow much more complex patterns of inheritance than the simple Mendelian either/or traits that we have seen in this chapter. In the next chapter we discuss some human traits that can be described as simple Mendelian traits, and many others whose inheritance is much more complex.Chapter SummaryThe study of those aspects of biological traits that are inherited is called genetics.Hereditary information is carried in the form of genes, which are parts of chromosomes.An allele is a variant of a gene. Dominant alleles show up in the phenotype when either homozygous or heterozygous. Recessive alleles are expressed only in the phenotype when they are homozygous. A genotype is the sum of an organism’s alleles.Plant and animal cells consist of two regions: a central portion called the nucleus, which contains the chromosomes, and a surrounding portion called the cytoplasm.Most cells in sexually reproducing species have the diploid number of chromosomes, and the chromosomes exist as homologous pairs. The gametes are an exception because they have the haploid number, including only one chromosome of each pair.In sexual reproduction, gametes fuse to form a zygote with the diploid number of chromosomes.Chromosomes are replicated and separated in mitosis during cell division, maintaining the diploid number and the full genotype.During gamete formation, meiosis halves the chromosome number to the haploid value and results in segregation of the alleles into different gametes.When two genes are located on different chromosomes, their alleles segregate independently during meiosis, undergoing independent assortment. When two genes are on the same chromosome, their alleles show linkage, staying together in meiosis unless crossing-over occurs.A karyotype is the full set of chromosomes from a cell, photographed during mitosis and arranged in homologous pairs by size, shape and banding patterns.One pair of human chromosomes differs between males and females; the chromosomes of this pair are called sex chromosomes.Sexual development in humans is coded for by many genes, including a gene on the Y chromosome.Genes that are on the X chromosome and not on the Y chromosome are called sex-linked genes.Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are two types of nucleic acid molecules.Each chromosome contains two very long spiral molecules of DNA, wound around each other, forming a double helix. The two strands are composed of complementary, not identical, nucleic acids. Genes are segments of one strand of the double stranded DNA.Prior to mitosis, DNA undergoes replication to produce two identical double helices. Replication requires enzymes, biological molecules that speed up chemical reactions but are not themselves changed in the reaction. The replication enzymes move along each DNA strand separately. On each DNA strand, the enzymes facilitate the addition of one nucleic acid at a time to produce a new complementary strand.PRACTICE QUESTIONSA pea plant that is homozygous tall (TT) produces male gametes of what genotype? What is the genotype of the female gametes it produces?If pollen from a homozygous tall pea plant fertilizes eggs from a homozygous short pea plant, what are the genotype(s) of the F1Sons? What are their phenotypes? What are the F's?1Genotype(s) and phenotype(s) when pollen is from a homozygous small plant and eggs are from a homozygous tall plant? if two F's1plants from the previous question were crossed, what genotypes would be among the F2Plant? In what proportion would they be? What are the genotypes and phenotypes of the offspring when the pollen is from F?1fertilized in question 2 eggs from a homozygous short pea plant? What about a heterozygous pea plant? How long is F?1Plants when plants homozygous for large yellow peas are crossed with plants homozygous for small green peas? What color are the peas? if the F1Are the plants in question 6 self-fertile? What are the genotypes, phenotypes, and phenotypic ratios of F?2 plants?If plants that are heterozygous for tall height and yellow peas are fertilized with pollen from plants homozygous for short height and green peas, what are the genotypes, phenotypes, and phenotypic ratios of the resulting offspring?If V represents the allele for violet-red color (dominant) and v represents the allele for white (recessive), what genotypes of offspring would be produced in each of the following crosses, and in what proportions?Vv ¥ vvVv ¥ Vvvv ¥ vvVV ¥ VVVv ¥ VVIf N is the number of structurally different chromosomes in a mammalian species, how many chromosomes does a liver or skin cell from this species have before it enters mitosis? How many chromosomes does one of the offspring cells have when mitosis is finished?If N is the number of structurally different chromosomes in a reptilian species, how many chromosomes does a cell of this species have before it enters meiosis? How many chromosomes does one of the offspring cells have when meiosis is finished?How many of the two attached chromosomes go to each end of the cell during anaphase of mitosis? How many of the two attached chromosomes go to each end of the cell during the first cell division of meiosis?Do homologous pairs of chromosomes line up together on the midline of the cell duringmetaphase of mitosis? Do homologous pairs of chromosomes line up together on the midline of the cell during the first cell division of meiosis?How many genes undergo DNA replication before mitosis? How many genes undergo DNA replication before meiosis?If a diploid cell containing 10 chromosomes divides by mitosis, how many centromeres are present:in the interphase cell?at prophase?at anaphase?in each daughter cell?If one strand of DNA contains the sequence TAGGCA,what is the opposite (complementary) DNA sequence?what mRNA sequence would be formed by this DNA sequence?how many codons are contained in this portion of mRNA?what anticodons of transfer RNA would bind to these codons?In Griffith’s experiment, which of the results were most unexpected? Why?Specify what type of individual would be formed from a human zygote containing each of the following:46 chromosomes, including two X47 chromosomes, including two X and a Y45 chromosomes, including one X and no Y46 chromosomes, including one X and one Y47 chromosomes, including two X and three copies of chromosome number 21IssuesHow did molecular genetics grow out of Mendel’s hypothesis? How do they help explain each other?How can we use the study of genetics to fight disease?Are there any inherent dangers of genetic research that we should be aware of?Is every genetic variant a defect?What are my genetic risks? What are my baby’s risks? How can I find out?Molecular genetics (RNA; transcription; translation; gene expression;DNA markers and genes)Human health and disease (human genetic diseases; disease predisposition; genetic testing)3Chapter OutlineWhat do Genes do?Gene expression: transcription and translation of genesMutationsSome Diseases and Disease Predispositions Are InheritedIdentifying genetic causes for traitsSome hereditary diseases associated with known genesGenetic Information Can Be Used or Misused in Various WaysGenetic testing and counseling Altering individual genotypes Altering the gene pool of populationsChanging the balance between genetic and environmental factors63Human Geneticsnervous couple sits in the waiting room, anxiously anticipating the results of a test. Their last child had lived her short life in almostconstant pain, and had died, blind, at age three, a victim of Tay–Sachs disease. The couple wants another child, but their previous experience was a heart-wrenching nightmare that they don’t want to go through again.They are awaiting the results of an amniocentesis, a technique that you will read about later in this chapter. A doctor enters the room with good news: the enzyme that her technicians were testing for is present in the amniotic fluid. The mother-to-be is carrying a child who will not get Tay–Sachs disease. The couple can look forward to raising a healthy child in a happy home.Scenes like the one just described are happening more often with each passing year. An increasing number of couples are undergoing medical procedures that did not exist when they themselves were born, seeking assurances that would have been unthinkable a mere 25 years ago.Tay–Sachs disease is one of a growing number of conditions that can now be diagnosed before birth. Along with physical characteristics, these conditions (traits) are passed on from one generation to the next.Some traits follow the simple Mendelian patterns of inheritance that we studied in the previous chapter. Many more, however, follow much more complex patterns because they are governed by multiple genes, each contributing a small amount to the trait. How do scientists find which genes are associated with which trait? Molecular biology has greatly changed how scientists go about the search. It has also changed what we mean by the concepts of ‘trait’ or ‘phenotype’ and has led to many new uses for genetic information.What do Genes do?In Chapter 2 we saw how the concept of the gene developed, culminating with the identification in the 1950s of DNA as the molecule of which genes are made. This discovery opened up a new line of research to explain exactly how a genotype results in a phenotype. As we will now see, genes act as the template for the synthesis of proteins, which then contribute in various ways to the production of a phenotype. The transition from DNA to protein involves two steps: transcription of DNA to another nucleic acid called RNA, followed by translation of RNA to protein. Together these two steps are called gene expression.Gene expression: transcription and translation of genesThe DNA containing the hereditary information is packaged in chromosomes. Each chromosome contains two very long strands of DNA (in humans the length of DNA in each cell is about 1 m or 3 feet). A gene is a segment of the DNA strand, that is, a subset of bases within the linear64 sequence of the whole DNA. Each person or pea plant (or any diploidindividual) has two chromosomes of each type, and thus has two genes for each hereditary trait, one on each chromosome of a homologous pair. Within a species, there may be any number of possible alleles for each gene, but each individual can only have two, one on each chromosome of a homologous pair.Genes (made of DNA) are expressed as phenotypes by providing information for the synthesis of RNA, which in turn provides information for the synthesis of protein. Often several proteins (and therefore several genes) interact to produce a phenotype. We can thereforeFigure 3.1The structure of RNA. The molecule as a whole is usually single-stranded, but short portions of some RNA molecules can base-pair with other portions of the same molecule. compare the nucleic acids DNA and RNA to blueprints that contain instructions for building proteins.a single strand of RNAURNA (Figure 3.1) differs from DNA in that (1) the back- C U C C bone contains the sugar ribose rather than deoxyribose, hence the name ribonucleic acid; (2) it is mostly singlestranded; and (3) the nitrogen-containing bases include uracil (U) instead of thymine (the other three nitrogenC C U GU AAU U AA A G CG C bases—adenine, guanine, and cytosine—are the same). In C CRNA, C pairs with G and A pairs with U. Genes undergo AAtranscription into RNA, meaning that information is Ctransferred from DNA to RNA, still within the language of U Cnucleic acids with their linear sequence of bases. The linear sequence of nucleotides in DNA determines the linear sequence of nucleotides in RNA. Some gene products stophere, as special types of RNA that have functions described later. The product of transcription for most genes is messenger RNA (mRNA), which then goes through a second information transfer (translation), in which the information is changed into another language, the language of amino acids. The linear sequence of nucleotides in messenger RNA determines the linear sequence of amino acids in the protein.Information flows from DNA to RNA to protein. This summaryUC G Cribose sugarC RPa nucleotide of RNAFigure 3.2Changing concepts of the flow of genetic information. statement has been called the central dogma of molecular biology (Figure 3.2A). As we see in Chapters 12 and 16, this central dogma has been considerably modified by the finding that information flow is not only in one direction. Proteins can affect the transcription of DNA and translation of RNA, and in some viruses RNA can be a tem-The central dogma of molecular biology,as it was understood in the 1960s: information flows from DNA to RNA and then to protein.DNA RNA protein plate for DNA synthesis. Moreover, one protein is not always the product of a single gene. Our current concepts of information flow are more accurately represented as a network (Figure 3.2B).Transcription—DNA to RNA. During transcription, a portion of DNA is used as a template to make a single-stranded mRNA. Theretranscriptionreplicationtranslation are several differences between transcription and DNA replication (see Figure 2.22, p. 58). In DNA replication, the whole length of both DNA strands is copied to make two new strands of DNA. In transcription, a small, discrete part of a single DNA strand is the template for the synthesis of RNA. The portions of a DNA strand that contain the necessary information to make different proteins are the genes. A particular gene is transcribed from only one of the DNA strands but, at a different place on the same chromosome, a different gene may be transcribed from the other DNA strand. Transcription begins when an enzyme (RNA polymerase) combines with a short DNAMany exceptions are now known. Forexample, some viruses, including the one that causes AIDS, have a ‘reverse transcription’ process in which RNA is used to make DNA. Also, many proteins influence the timing and amount of gene transcription and RNA translation.DNA RNA proteinFigure 3.3The transcription of DNA into RNA.sequence marking the beginning of a gene (Figure 3.3). The enzyme causes the DNA of the gene to unwind, allowing RNA bases to pair with the nucleotides of the gene. Nothing happens on the other DNA strand. The RNA nucleotides become bonded together to form the backbone RNA strand. Finally the RNA strand comes off its DNA template, allowing the DNA to twist back into its double helical shape.The product of transcription is usually mRNA, which carries the information for protein synthesis. Two other forms of RNA that function in protein synthesis, transfer RNA and ribosomal RNA, are also transcribed from DNA, but are not themselves translated into proteins. Several proteins are known that can either inhibit or enhance transcription, providing a means by which the amount of RNA being made can be controlled (see Figure 12.5, p. 420).Translation—RNA to protein. Transcription to mRNA is followed by translation, during which the mRNA sequence of nitrogenous bases isEnzyme binds to a DNA strand at the beginning of a gene.Enzyme unwinds a portion of the double helix, separating the strands locally. RNA nucleotides pair one at a time with the complementary nucleotides on one DNA strand. parent DNAC GA TC GT AG CA TenzymeOther enzymes join the new RNA nucleotidesto form a continuous RNA strand, complementary to one of the DNA strands.The RNA molecule separates, and the DNA strands pair once more.C GA A TC C GT U AG G Cnew RNAA T strand unchanged DNAtranslated into a sequence of amino acids that make up a protein chain. Translation uses groups of three successive nitrogenous bases on the mRNA as coding units, or codons. Each codon corresponds to one amino acid.Translation uses all three forms of RNA: mRNA as the template, transfer RNA to match a codon with an amino acid, and ribosomal RNA to form the ‘scaffold’ on which the process takes place. Each mRNA codon pairs with a complementary three-base sequence called an anticodon, which is part of the transfer RNA (tRNA) molecule (Figure 3.4). Each tRNA molecule has a specific anticodon and carries a specific amino acid molecule that it can transfer to the growing protein chain during protein synthesis, but this addition only takes place if the anticodon matches the next mRNA codon.The mRNA and tRNAs are held in the proper relation by a particle called a ribosome, containing both protein and ribosomal RNA (rRNA) (Figure 3.4). As each mRNA codon is bound by its complementary tRNA anticodon, one amino acid is added at a time to the growing protein. The next three nucleotides on the mRNA form the next codon, ready for the corresponding tRNA anticodon to bind. The process repeats until the end of the mRNA is reached and the protein is complete (Figure 3.5).Proteins and phenotypes. There are about 20 different amino acids that can be combined to make proteins. Proteins are linear, unbranched chains of these amino acids. After the chains have been synthesized by translation, they fold into complex shapes that determine their function. How they fold depends on the sequence of amino acids (for more on protein structure see Figure 10.5, p. 334).The relationship between proteins and phenotypes is actually twofold. At the molecular level, it can be said that the protein itself is the phenotype for its gene. At the level of the organism (the level at which Mendel described visible phenotypes) proteins work together with other proteins and with other types of molecules to result in the phenotype. A phenotype can be altered by changes in the DNA.MutationsDNA occasionally undergoes permanent heritable changes of its sequence of nucleotides. These changes are known as mutations. Some of these can result from mistakes during DNA replication, or they may beFigure 3.4The roles of transfer RNA (tRNA) and ribosomal RNA (rRNA) in translation. In the example shown here, the mRNA codon CUU matches the tRNA anticodon GAA, which corresponds to the amino acid carried by the tRNA, phenylalanine, abbreviated Phe. The ribosome containing rRNA holds the tRNA in place on the mRNA.Phe amino acid caused by chemical or physical agents (such as ultraviolet light and radiation—see Chapter 12). Most mistakes and damage are immediately fixed by various self-correction mechanisms and so do not persist.There are two general types of mutation:base substitution; (2) base insertion or deletion. The simplest kind of mutation is a single-base substitution (called a point mutation), such as the substitution of one nucleotide (A, G, C, T) for another. BecauserRNA in ribosometRNAanticodonG A AA G A AU C U U UcodonmRNAFigure 3.5Translation of a nucleic acid sequence into a protein.Each group of three bases in messenger RNA (mRNA) serves as a codon to determine what amino acid is to be inserted next into the protein sequence. The ribosome holds the mRNA while tRNAs bring successive amino acids to the growing protein chain.substitutions of this kind change the mRNA codon, they may result in the wrong amino acid being inserted into a protein chain (Figure 3.6A). The number of nucleotides has not changed; only one codon, and therefore at most one amino acid, is changed in the growing protein chain.Larger changes occur when one or two extra nucleotides are inserted into a DNA sequence, or when one or two are deleted from the sequence. Mutations that change the number of nucleotides change all of the codons that follow the point of insertion or deletion. This is because the DNA or RNA code contains no ‘commas’ or other ‘punctuation’ to signify where a new codon starts. Each new codon is simply the next three bases after the previous codon, so the first codon determines the starting point for the second, and so on. If an extra base is inserted or a base is deleted, that codon and all codons that follow the mutation are changed or shifted over. (Hence this type of mutation is often called a frameshift mutation, and we say that the reading frame has shifted.) In the example shown in Figure 3.6B, a deletion of a G causes a change in mRNA codons from that point on, leading to the wrong amino acids’ being added to a growing protein during translation. CGT in DNA is transcribed to the complementary GCU in mRNA, the codon for the amino acid alanine (Ala). By removing G, the DNA sequence becomes CTC, which is tran-scribed to the complementary mRNA codon GAG. GAG is the codon for the amino acid glutamine (Glu), not Ala. Note that the C that would have been part of the next codon is now part of the Glu codon. All succeeding codons ribosome protein underconstructionmRNAdirection of movement of ribosomes along stationary mRNAgrowing protein chainmRNAstrandare likewise shifted, leading to a protein with different codons and therefore a different amino acid chain from that coded by the unmutated DNA strand. Because so many amino acids are affected, most mutations of this kind result in nonfunctional proteins.As mentioned earlier, protein function depends on the tRNA4 binds to its mRNAcodon, bringing amino acid 4 to the growing protein.growing protein chain2STEP 2 Amino acid 4 attaches to thechain; tRNA3 can then leave.2 3shape of the folded protein molecule. A substituted amino acid may alter the protein shape and therefore change or impair the pro-1 3 4ribosometRNA1 4 tein’s function. The moreamino acids that are changed, the more likely it is mRNA3 4 (containing rRNA) 3 4that this change alters protein function. Phenotypic consequences of inserting achanged amino acid run the gamut from those that are undetectable to those that are fatal, but changes that affect many amino acids at once are more often harmful or fatal.Mutations that persist in somatic (body) cells can cause problems in the individual carrying the affected genetic material (see Chapter 12), but the change will not be passed on to the next generation. Only mutations in cells that give rise to gametes may be passed on to future generations and thus have a role in evolution. We owe the rich diversity of genes in the world’s species to the creation of different alleles, which originate as mutations. Mutations are also useful to the scientist because they serve as essential tools in the laboratory.Figure 3.6Examples of two types of mutations. Glu, Leu, etc. are abbreviations for different amino acids.Single nucleotide substitution. When, for example, a C is substituted for a G in the DNA strand, the mRNA codon matches with the tRNA carrying the amino acid glycine rather than the tRNA carrying the amino acid alanine.PheAlaValAAACGTCAA etc.AAACCTCAA etc.PheGlyValChange in the number of nucleotides. When, for example, a G is deleted from the DNA strand, the codon that had the G and all subsequent codons are misread and different amino acids are placed in the chain.PheA AAlaVal Ala Ser Val LeuA APheGluLeuHisProPhe1 DNA has been called the master molecule because it controls (or determines) RNA sequences, which control protein sequences, which (as enzymes) control the cell’s other activities. Is the term ‘master molecule’ an accurate description? Does the language of control (e.g., DNA controls the type of RNA produced) say more aboutTHOUGHT QUESTIONSthe molecules or about the scientists? Does the use of a word such as ‘master’ suggest a hierarchical approach in which information flows in one direction only?2 The term ‘mutation’ often has a negative connotation. Is mutation always ‘bad’?Figure 3.7An example of simple Mendelian inheritance in humans. Albinism, a recessive trait, arises in most cases from matings between heterozygotes, although it could also arise from matings between a heterozygous person and someone who is homozygous recessive.Some Diseases and Disease Predispositions Are InheritedEarly in the twentieth century, pioneering geneticists discovered that Mendel’s rules, formulated on the basis of experiments with pea plants, could also explain the inheritance of many human traits. For example, albinism is a total lack of melanin pigment in the skin, eyes, hair, and the body’s internal organs, and the inheritance of albinism follows Mendel’s rules. The skin of albinos is white and their hair is white as well. One of the normal functions of melanin is to block ultraviolet light, and albinos sunburn easily and are very sensitive to bright lights. All geographical races of humans have albino individuals, as do many other species.The inheritance of albinism is shown in Figure 3.7. A recessive allele is responsible for this condition and thus it can be transmitted withoutA family in which only one parent is heterozygous; none of the children are albinos.A family in which both parents are heterozygous; each child has a 1 in 4 chance of being an albino.PARENTSnormal pigmentnormal pigmentAAnormal pigmentAa normal pigmentAa AaGAMETES all A 11PLAYER1111AA AaAA AaAa aa CHILD (male or female) CHILD (male or female)1 AA1 Aa1 AA1 Aa1 aa normal pigment normal pigment3of normally pigmented children1 of children albino©Human pedigree for a family with albinism; the short horizontal lines between a male and female represent matings that produced the children in the row below.female malenormally pigmentedalbino detection through many successive generations of normally pigmented individuals (Figure 3.7A and C). However, matings between heterozygous individuals may produce albino children (Figure 3.7B). The likelihood that both parents are heterozygotes is increased if mates are chosen from among related persons such as cousins (see Figure 3.7C). This is because the same rare recessive alleles are more likely to be present in other family members than they are in the general public. Diagrams giving the pattern of mating and descent, as in Figure 3.7C, are called pedigrees.Shortly after the rediscovery of Mendel’s laws, an English physician, Archibald Garrod, made an important discovery: Mendel’s laws applied not only to visible characteristics such as eye colors and albinism, but also to certain medical conditions. Garrod’s identification of the genetic basis of a condition called alkaptonuria is described later in this section.Identifying genetic causes for traitsBefore searching for genes that cause a particular disease or trait, we first need to know whether there is any basis for thinking that the disease is inherited. As we will see, some diseases are the direct result of particular gene mutations. In other diseases, genetic effects are indirect and contribute to disease susceptibility, the likelihood that a person will get a disease. Susceptibility to many diseases seems to have a hereditary component. However, certain disease susceptibilities and many nondisease traits are the result of the interaction of multiple genes, not the result of mutations in single genes.Several kinds of studies are used in answering the question of whether a disease or other trait is inherited.Pedigrees. Geneticists have several ways of studying human hereditary traits. One of the most basic methods is to present the available data in pedigrees, as in Figure 3.7C. Pedigrees are most useful when they span many generations and hundreds of people, or when separate pedigrees are available for hundreds of different families. The study of pedigrees can help to identify whether a condition is inherited, and permit us to determine which traits are dominant, which are recessive, and which have a more complex genetic basis. If the genetic basis of a trait is complex, or not fully known, then pedigrees can also help in an empirical determination of risks, including medical risks. For example, a child has a greatly increased risk of having insulin-dependent diabetes mellitus if one or both of the child’s parents has the disease. The term risk has a precise statistical meaning: it is the probability that a particular condition will occur or that a particular condition will be inherited.Studies of twins and of adopted children. Studies of twins are sometimes useful in suggesting the extent to which the presence of a trait can be explained genetically, rather than environmentally. In such studies, numerous twin pairs are located in which at least one twin has the condition being investigated. For pairs of this kind, the frequency with which the other twin has the condition is studied. This frequency is called the rate of concordance. For the vast majority of traits, studies on twins find that a mixture of both heredity and environment is involved. Traits under strong genetic control usually have a higher frequency of both twins sharing a trait when they are monozygous twins (identical twins, derived from a single fertilized egg) than when they are dizygous twins (fraternal twins, derived from two separate eggs). In contrast, traits with mainly environmental causes have similar rates for both types of twins.Adoption studies can also provide important clues about whether a particular trait is heritable: if adopted children show a higher rate of concordance with their birth parents than with their adoptive parents, then the hypothesis of a genetic cause is made stronger. Some researchers have, however, criticized this type of study because adoption agencies do not place children at random but purposely try to match children with adopting parents whose backgrounds are similar to the backgrounds of the children’s birth parents. This practice introduces a bias that raises the concordance rates between adopted children and the parents who adopted them. Another complication is that many children are adopted by relatives. This makes it very difficult to sort out which similarities are environmental and which are genetic.Linkage studies. Once evidence has been found that there is a genetic basis for a trait, linkage studies can help locate the relevant gene or genes. To do this, we first need a set of DNA markers, pieces of chromosomes that are visibly different under the microscope or short sequences of DNA that can be revealed by the molecular techniques discussed later in this chapter. If we can locate a DNA marker whose pattern of inheritance is the same as the pattern of inheritance of the trait, then we can conclude that a gene associated with the trait is located near the marker. One problem is that we may at first not know where to look, so we need many markers, scattered across all the chromosomes. Also, large pedigrees are needed to carry out this type of analysis. After a linkage between DNA markers and a trait has been found, other molecular techniques are used to close in on the actual gene. Finally, after the gene has been located, its full sequence can be determined.In the past, genes that did not assort independently were found to be on the same chromosome and we say they are linked. The frequency of crossing-over was used as a measure of the distance between genes (see Chapter 2, pp. 45–46). If linkage to a visible chromosomal abnormality could be established, then the group of genes could be assigned to a particular chromosome. These classical genetic techniques were developed in other species, using hundreds or thousands of offspring in each generation to assess cross-over frequencies. These techniques could not be used on humans because humans have such small family sizes and such a long generation time, and because humans cannot be bred for experimental purposes. Before 1980, very few human genes had been mapped to their chromosomal locations.DNA markers. Several marker systems have now been discovered for studying human DNA and human genetics. DNA contains, in addition to genes, non-coding regions that vary from one individual to another in their length or their sequence. Many of the markers are in these non-coding regions of DNA. The first of these DNA marker systems was discovered in 1980, and was called restriction-fragment length polymorphisms (abbreviated RFLPs and pronounced ‘riflips’). Restriction fragments are short pieces of DNA produced by cutting the DNA with specific enzymes called restriction enzymes, which we will see more about in Chapter 4. These fragments are useful markers because they are different lengths indifferent people, and therefore one person’s DNA can be distinguished from another’s. There are only a limited number of RFLPs in the human genome, however. More recently, other DNA markers have been discovered that occur with greater frequency throughout the genome than do RFLPs. Each of these is a short, unique DNA sequence with a known location in the genome. Each DNA marker sequence exists in different alleles; that is, the sequence varies slightly from one person to another, again allowing one person’s DNA to be distinguished from another’s. For some DNA markers the same sequence is repeated a variable number of times (microsatellite markers). For other DNA markers some nucleotides differ from one allele to another. These include expressed sequence tags, small portions of genes that vary from one person to another, and singlenucleotide polymorphisms, sequences located either in genes or in noncoding DNA regions that differ by a single nucleotide.Each different marker can be detected by a specific DNA probe, a piece of DNA with a sequence complementary to the marker sequence. When a radioactive DNA probe is added to some DNA, the DNA picks up the radioactivity if it contains the marker sequences that can pair with the probe. DNA probes cause only those fragments to show up that have sequences complementary to the probe sequence. For markers such as microsatellites or RFLPs that vary by length, the alleles can be distinguished by length after separation by electrophoresis (Figure 3.8). For markers that differ by sequence, a different DNA probe is required forFigure 3.8Microsatellite DNA marker alleles can be distinguished by the distance they travel during electrophoresis.The microsatellite differs in length depending on the number of repeats that exist within it. In this example, the allele from the father is shorter because it has fewer repeats than the allele from the mother, which is longer because it has more repeats.(B) AMPLIFICATION OF MICROSATELLITE BY PCR(Using techniques shown in Figure 3.12.)DNA from a pair of chromosomes chromosomefrom father...TCTGAGAGAGGC...chromosome from mother...TCTGAGAGAGAGAGGC...repeat sequence© SEPARATION BY ELECTROPHORESISThe mixture of microsatellite PCR products is placed on a gel and exposed to an electric field. Because DNA has a negative charge,the pieces move toward the electrode of positive charge. In the time that the current is on, smaller pieces travel farther through the gel than the larger ones do.electric field+agrose gel electrophoresis(D) DETECTION WITH A PROBENone of the pieces can be seen; however, they can be detected with a variable-repeat probe tagged radioactively orchemically (bands shown in color). The probe is a small piece of DNA with a sequence complementary to the sequence of that variable repeat, so the probe will bind to those pieces of DNA containing that variable repeat. The probe thus does two things: it identifies pieces with that specific repeat and it allows scientistsDNA fragment not boundby the probelonger piece from mother’s chromosomeshorter piece from father’s chromosomedirection of travel to determine whether the sequence is repeated a few times (to givea short DNA piece that travels farther) or many times (to give a long piece that travels a shorter distance within the gel).Figure 3.9Using DNA markers to establish a linkage between a DNA region and an inherited phenotype.each allele. These DNA probes are clustered onto a solid surface called a DNA chip, or microarray. A fluorescently labeled sample of DNA is added. If the DNA sample contains the complement to the DNA probe, it binds and a microscope attached to a computer detects its fluorescence. One million DNA probes can be placed on a one square centimeter microarray, so that two alleles of each of a half million markers can be tested at the same time.Such marker sequences have been identified throughout the DNA of humans and their chromosomal locations and genetic map positions have been established. Geneticists use all of these different types of markers in developing linkage maps. Because the chromosomal locations of the markers are known, geneticists can determine the positions of presumed genes located near the markers by finding a pattern of linkage between the trait and the marker. DNA samples are collected from members of a family with a pedigree in which the trait appears. Molecular geneticists then search the DNA samples for a marker, among the thousands of markers known, that is inherited within the family in the same pattern as the trait of interest. If all the individuals within a large pedigree who have a particular trait have a specific DNA marker, and all those without the trait do not have the marker, the gene for the trait is presumed to be located near that marker (Figure 3.9A). For the other markers that are not in the vicinity of a gene linked to the trait, theMarker 1, detected by probe 1, is linked to the trait father’s marker alleles mother’s marker allelespedigreemarker from mothermarkers from fatherunaffected female unaffected maleaffected individualThe father has the trait and is heterozygous at marker 1. The mother does not have the trait and is homozygous at marker 1; the mother’s marker allele has a greater number of repeats than either of the marker alleles from the father’s DNA.The children who have the trait have one of their father’s length of microsatellite marker. The child without the trait does not. The marker lengths detected with probe 1 thus follow the pattern of inheritance of the trait, indicating that an associated gene may be nearby.Probe 2 detects a different microsatellite marker, and shows that it is not linked to the trait father’s marker 2 alleles mother’s marker 2 allelespedigreeA child with the trait and a child without the trait have the same band pattern for the marker detected by probe2. The marker detected by probe 2 is therefore not near any gene associated with the trait. mother’s and father’s markers can be found in the children, but the pattern of bands does not follow the pattern of inheritance of the trait (Figure 3.9B). In this way, an increasing number of presumed gene locations are being discovered at an accelerating rate.Identifying a specific gene as the cause of a trait. It is important to understand that DNA markers are not the genes themselves. In other words the linkage indicates the approximate location of a gene of interest. It does not tell us what the gene is, or what its function is, or what alleles are associated with disease or nondisease.Often when such a location has been identified, news reports are published claiming that ‘the gene for X’ has been discovered, but no gene has even been investigated, only a DNA region that maps with the trait. When a linkage area has been identified, sequence databases can be consulted to see what genes are known in this area of the chromosome. If genes are known, their protein products can sometimes be deduced from the nucleotide sequence and those proteins can be further investigated for their connection with the trait or disease. Often, however, the genes within a linkage area have not yet been identified, and neither their protein product nor their function is known.The first gene to be located by using DNA molecular markers was the gene for Duchenne’s muscular dystrophy, which is located on the X chromosome. Other diseases for which linkage areas were located and identified during the 1980s and 1990s include Huntington’s disease (chromosome 4), cystic fibrosis (chromosome 7), Alzheimer’s disease (chromosome 21), one form of colon cancer (chromosome 2), and two forms of manic depression (chromosome 11 and the X chromosome). Of these linkage areas, genes have so far been found for muscular dystrophy, Huntington’s disease, and cystic fibrosis. Among these diseases, only cystic fibrosis seems to be inherited on the basis of single-gene Mendelian genetics. Even in cystic fibrosis, how the gene product produces the disease is not fully understood.Some hereditary diseases associated with known genesSome human diseases that follow simple Mendelian genetics were identified early in the twentieth century. Genes for some other diseases have been found recently by using DNA markers. In this section we consider some hereditary diseases whose underlying genes are known. In some cases the mechanism by which the gene mutation produces the disease is known, but for others, although the full DNA sequence of the gene and its mutations may be known, the mechanism by which these result in disease is not.Alkaptonuria. Alkaptonuria is a rare condition in which a patient’s face and ears may be discolored and in which their urine turns black upon exposure to air. Archibald Garrod, mentioned earlier in this chapter, tested the urine of these patients and discovered that the color is caused by an acid. We now know that this substance, homogentisic acid, is formed in the course of breaking down the amino acid tyrosine. In most individuals, the homogentisic acid can be broken down harmlessly with the help of an enzyme. However, in patients with alkaptonuria, the necessary enzyme is missing or defective. Garrod realized that an error in an important biochemical (metabolic) process was responsible, and heFigure 3.10Biochemical pathways for three inborn errors of metabolism: phenylketonuria, alkaptonuria, and albinism.called this type of condition an “inborn error of metabolism”. He studied the families of individuals with alkaptonuria and two other such conditions, including albinism, and found a common pattern: each of these inborn errors of metabolism was inherited as a simple Mendelian trait, and in each case the lack of a functional enzyme was recessive. Many other inborn errors of metabolism have since been discovered and their biochemical defects identified. Each of these inborn errors is caused by a recessive allele, the product of a DNA mutation that, when transcribed and translated to its protein product, changes a functional enzyme into a nonfunctional one. Alkaptonuria, albinism, and the condition called phenylketonuria, which is described next, all arise from errors in a series of closely related metabolic pathways (Figure 3.10).Phenylketonuria. Phenylketonuria (PKU) is a genetically controlled defect in amino acid metabolism. The amino acid phenylalanine, which is present in most proteins, is normally converted by an enzyme into another amino acid, tyrosine; the tyrosine is then broken down by the pathway shown in Figure 3.10. A defect in the enzyme that usually confrom proteins from proteins dopamine (see Chapter 13) phenylalanineblocked in phenylketonuriatyrosine DOPA(alternative path in phenylketonuria)blocked in albinismphenylpyruvate (accumulates in phenylketonuria)p-hydroxyphenylpyruvate
CO2
normally melanin (black, brown) and pheomelanin (red, yellow) pigments formhomogentisic acid (accumulates in alkaptonuria)blocked in alkaptonuriaKEY:carbon atom oxygen atom nitrogen atom hydrogen atom normally breakdown products enter Krebs cycle verts phenylalanine to tyrosine causes the phenylalanine to be processed by an alternative pathway. A product of this alternative pathway accumulates in the blood and in all cells, acting as a poison that causes most of the debilitating symptoms of the disease: insufficient development of the insulating layer (myelin) around nerve cells, uncoordinated and hyperactive muscle movements, mental retardation, defective tooth enamel, retarded bone growth, and a life expectancy of 30 years or less. Thus a change in one gene (and one enzyme) can have many phenotypic consequences throughout the body.Fortunately for people carrying this genetic defect, a simple test for its presence exists. If phenylketonuria is detected at birth or earlier, it is possible to avoid the symptoms of the disease by greatly limiting those foods that contain phenylalanine (nearly all proteins, including breast milk), and diet foods and soda containing the artificial sweetener aspartame, which is metabolized to phenylalanine. Small amounts of pheny-lalanine are essential in protein synthesis (see Chapter 10), but the diet must be carefully monitored to guard against the larger amounts of phenylalanine whose breakdown products would be in toxic amounts that cause the disease symptoms.Alkaptonuria and phenylketonuria are inherited via single recessive alleles that follow Mendel’s laws. Yet these traits are medical conditions, rather than visible traits like those studied by Mendel. New findings thus broadened the concept of a ‘trait.’ The concept has been broadened further by the discovery of a genetic basis for diseases that are not just present or absent but that show a range of severity in different people.Duchenne’s muscular dystrophy. Duchenne’s muscular dystrophy is a sex-linked genetic disorder that causes muscles to become weak and nonfunctional. In most cases, the inability of the muscles of the diaphragm to keep the patient breathing leads to death during the teenage years or in the early twenties. After the gene responsible for this disease was located by linkage studies using DNA markers, its protein product, dystrophin, was found. So far, this discovery has not led to new therapies for the disease, but the research on dystrophin is greatly adding to our understanding of normal muscle contraction, and it is hoped that this knowledge will lead to effective treatments.Cystic fibrosis. Cystic fibrosis is the most common genetic disease among the white population in the United States and much of western Europe. Cystic fibrosis is characterized by thickened fluids, especially the fluids that line the lungs. Normally, as these fluids are cleared from the lungs, they remove respiratory bacteria, preventing infections. The thicker-than-normal fluids of cystic fibrosis are not cleared from the lungs as they should be, so people with cystic fibrosis have breathing difficulties and frequent lung infections.Cystic fibrosis was mapped by linkage studies to a region on chromosome 7 and later a gene was identified. The product of that gene is a membrane transporter, a protein that carries ions, chloride in this case, into or out of a cell. A very large number of different mutations have now been found in the gene for this transporter protein. Some mutations lead to few or no symptoms; some are associated with more severe disease. However, no particular mutation is completely predictive of disease onset or severity. Although identification of the gene and its product has increased our understanding of the disease mechanism, it is still not known how the mutations lead to the many symptoms of the disease.Huntington’s disease. Huntington’s disease (or Huntington’s chorea) is a neurological disorder that typically begins in middle age with uncontrollable spasms or twitches of the hands or feet (see Chapter 13, p. 474). As the disease progresses, the spasms become more pronounced, and the patient gradually loses conscious control of all motor functions and of mental processes. The disease progresses slowly, but is invariably fatal. American song writer and balladeer Woody Guthrie died of Huntington’s disease. Although it is always lethal, Huntington’s disease does not appear until after its victims have lived through their prime reproductive years, during which they may have passed the mutation to their children. Studies of family trees show that Huntington’s disease is inherited as a dominant trait. The gene responsible for the disease was located on chromosome 4 in 1983. This gene was fully isolated and identified in 1993, but its normal function remains unknown.Subsequent studies have shown that Huntington’s disease is associated with a different type of DNA mutation, called a dynamic mutation. Most mutations are rare, stable, and inherited unchanged from one parent or the other. In dynamic mutations, a three-nucleotide segment is repeated many times, increasing in number during mitosis in different tissues. The number of copies can also change during meiosis, so a child may inherit more copies of the repeat than is present on either parent’s chromosome.The allele that causes Huntington’s disease differs from the other alleles of the gene in having many extra repetitions of the threenucleotide sequence AGC. Persons with fewer than 30 repeats are unlikely to get the disease. Persons with more than 38 repeats are almost certain to get the disease, with the age of onset being younger when there are more than 50 repeats. A test for the allele responsible for Huntington’s disease has since been devised, but there is a problem in interpreting it because there is an overlap in the number of repeats associated with a particular outcome. The ‘normal’ range in number of repeats is 9–37, but some people with as few as 30 repeats have become ill. Because the number of repeats can increase during meiosis, people with 30–37 repeats may pass the disease to their offspring.Huntington’s is one of several diseases, called trinucleotide repeat diseases, associated with dynamic mutations. Another is fragile X syndrome, the most common type of hereditary mental retardation, in which the repeat is CCG in a gene on the X chromosome. The gene has been identified but its normal function remains unknown.Genes increasing susceptibility to disease. The transmission of human traits controlled by single genes follows the rules that Mendel developed for peas. The situation is more complex when we study phenotypic traits such as height or skin color that are controlled by many genes at once and that are also influenced by environmental variables such as nutrition.Genes have now been found that do not lead directly to a trait (such as a disease) but increase the probability that some trait or disease will develop. Having a particular allele of these genes does not mean that a person is certain to get a particular disease, only that the likelihood of their doing so is higher than that in people with other alleles. These genes, like all genes, code for proteins. The proteins associated with susceptibility are often regulatory proteins that change the body’s response to some environmental factor. The genes have sometimes been called susceptibility genes, although ‘genes associated with increased susceptibility’ is a more accurate description. Those associated with predisposition to cancer, discussed in Chapter 12, are examples. As we mentioned earlier for other multigene traits, we must be cautious not to think of these ‘susceptibility genes’ as simple, either/or, Mendelian alleles.In many cases all we know at present is a statistical association between some traits and some DNA markers; the genes themselves have not yet been identified. Traits such as bone density or obesity in mice, and behavioral traits such as ethanol consumption by rats, have been found to each be associated with several DNA markers, but no genes have yet been identified. Despite this, news stories have overplayed such statistical associations, referring, for example, to the ‘gene for obesity.’ Such terms are premature and surely oversimplified. Each of these traits is influenced by multiple genes, so we cannot think of them as we think of Mendelian either/or traits. These traits vary along a continuum and are not just present or absent like those studied by Mendel. Thus the concept of a single gene determining a single trait does not apply. A single gene codes for a single protein, but the amount of that protein produced depends on what other genes and proteins are present. It is the interaction of them all that results in the trait.What is the difference between a genetic marker and a gene?Is research on genetic diseases important for society even if it does not lead to new methods of treatment?With our thinking influenced by genetic diseases like PKU or Huntington’s disease, we have been accustomed to thinking ofTHOUGHT QUESTIONS‘mutations’ as ‘defects.’ Not every mutation is a defect, however. With genetics research now turning to the identification of disease susceptibility, it is likely that we will all turn out to have a hereditary predisposition to something. Do new research directions necessitate reconceptualizing the term mutation as ‘variation,’ rather than ‘defect’?Genetic Information Can Be Used or Misused in Various WaysAfter a genetic basis has been identified for a particular trait, what happens next depends in a large part on the values that individuals and society place on that trait. We have considered in this chapter many traits that at least some people consider undesirable, although not all of them impair health or longevity. In many cases, but not others, we can identifyFigure 3.11Techniques for prenatal detection of genetic conditions.a specific gene that fails to make a functional protein of some sort. These are often called genetic defects, a category that includes all inborn errors of metabolism such as those shown in Figure 3.10. The term genetic defect thus means that a specific allele and its product are defective; it does not mean that the person bearing the gene is defective. For this reason, many people prefer terms such as genetic disease or genetic condition, rather than genetic defect.Humans can deal with hereditary conditions and hereditary risks in many ways. We can conveniently describe four broad categories of response: gathering and sharing information through genetic testing and counseling, changing individual genotypes, changing the gene pool at the population level, and changing the balance between genetic and environmental factors. Many of the methods in these four categories, which we consider below in turn, raise important ethical questions. The ethical questions can be summarized as follows.Who decides who should be tested?Who has access to the results of the test?What are the responsibilities of a person who carries a gene for a hereditary disease?Do we have a responsibility to maintain genetic diversity?Who determines what traits (if any) are called ‘defects’? Think about these ethical issues as you read the rest of the chapter.Genetic testing and counselingAdvances in medical genetics have led to better ways of detecting genetic diseases and to ways of detecting them earlier. Identification of chromosomal variations, mutated alleles of genes, or products of mutated alleles may allow the detection of a disease at the earliest possible stage.Prenatal detection of genetic conditions. Some conditions can be detected before birth, in utero (literally, ‘in the womb’). From conception until about the eighth week of pregnancy, a pregnant woman is carrying an embryo; from the eighth week until birth, the term fetus is used rather than embryo. In the technique of amniocentesis (Figure 3.11A), a small amount of fluid (amniotic fluid) is withdrawn from the sac in which the fetus is developing in the mother’s uterus (see Chapter 9, pp. 302–303). The fluid itself is analyzed for the presence or absence of certain enzymesamniotic cavity placentaextract amniotic fluidfetal cells in amniotic fluid(B) CHORIONIC VILLUS SAMPLINGultrasound locator usedto monitor correct placementvilli of chorionremove sample of chorionic villifetal cellsuterus wallgrow cells in culturegenetic analysisuteruswall placenta flexible cathetergrow cells in culturegenetic analysis that might indicate a genetic defect in the fetus. Also, amniotic fluid usually contains cells that have been shed from the surface of the fetus. Growing the cells in the laboratory can reveal additional information.Instead of amniocentesis, chorionic villus sampling is sometimes used for prenatal detection. This technique is a type of biopsy (removal of living tissue for examination) of the placenta (Figure 3.11B). The placenta is the structure by which the fetus attaches to the wall of the uterus (see Chapter 9, pp. 300–301 and Chapter 14, pp. 530–531). Because the part of the placenta biopsied is tissue derived from the fetus, not from the mother, the cells sampled by this technique are fetal cells. Chorionic villus sampling can be performed earlier in pregnancy than amniocentesis can. Certain low but nonzero risks are associated with amniocentesis or chorionic villus sampling, including a risk of mechanical injury to the growing fetus and a risk that the pregnancy will be prematurely terminated. Because of these risks and other reasons, these tests are not performed routinely on every expectant mother.After fetal cells have been obtained by either amniocentesis or chorionic villus sampling, chromosomes from these cells are analyzed for evidence of Down, Turner, or Klinefelter syndromes. Also, if there is a reason to study a particular gene, its sequence can be determined by comparing it with a known sequence for that gene. This cannot be done on the minute amounts of DNA that exist in the cells unless these amounts are first increased, or amplified. Amplification of DNA is accomplished by the polymerase chain reaction (PCR) (Figure 3.12). The polymerase chain reaction is often used to detect genetic conditions by using DNA from eight-cell embryos before implantation. These embryos are derived from in vitro fertilization (literally ‘in glass’), meaning that the fertilization of the egg by the sperm took place in laboratory glassware rather than inside the body (in vivo). One of the eight cells can be removed for genetic testing and the other seven can be implanted into a woman’s uterus to grow to term.Several dozen genetic diseases are now detectable through prenatal tests, including Tay–Sachs disease, cystic fibrosis, and phenylketonuria. separate DNA strands and add primerDNAsynthesisseparate DNA strands, add primers againDNAsynthesisDNA marker primersregion of double-stranded chromosomal DNA to be amplifiedFigure 3.13Two ways of assessing risk for a recessive trait with single-gene, simple Mendelian inheritance.Testing newborns or adults. Other tests are done on newborns or on adults. Tests that are simple and inexpensive can be used for mass screening. For example, many hospitals routinely screen all infants at birth for phenylketonuria (by a blood test to detect the amino acid phenylalanine, not by a DNA test). Such screening is considered ethical because it is done on all infants and it is a clear benefit to the infant for the information to be known. Tests that detect heterozygosity for defective alleles (e.g., testing for carriers of the allele causing sickle-cell anemia; see Chapter 7) can be performed on adults before they become parents. Those undergoing this type of screening must first give their informed consent. They must sign a form stating that they understand the nature of the test, the possible outcomes (including the conditions that the test can detect and the likelihood that the genotype will result in a disease phenotype), the possible risks of the procedure, and the possible benefits. People in these situations often consult a genetic counselor to help them understand the test and the risks before giving their consent. For example, they can be advised that if they are identified as being heterozygous and they have children with a person also heterozygous for the same allele, each of their offspring has a 25% chance of being homozygous for the recessive condition. (To understand why, refer back to Figure 3.7B.) The extent to which homozygosity predicts disease severitydiffers with the disease.Who should be tested? Genetic testing is expensive and it would not be reasonable to test everyone for all genetic disorders. So an effort is made to identify persons at higher risk of having certain defective alleles. Figure 3.13 shows two ways in which risk is estimated. First, family history identifies persons at higher risk and may prompt testing because having a family history of a genetic condition increases the probability that a family member carries the defective allele (see Figure 3.13A). However, because recessive traits show up phenotypically only when the genotype is homozygous or sex-linked, a recessive trait may not show up in a pedigree and a person may not know the family history. A second way of estimating risk is by the population frequency of a trait (that is, how many people have the trait in a given population). The likelihood of carrying aEach child of two parents heterozygous for a recessive trait has a 25% probability of being homozygous recessiveIf 1% of a population expresses a trait known to be recessive (meaning that those who express the trait are assumed to be homozygous), 18% can be assumed to be heterozygous. Out of 100 individuals shown here, 1 is homozygous for the recessive trait and 18 are heterozygous.KEY:malesfemales homozygous for dominant traithomozygous for recessive traitheterozygous recessive allele for a particular condition is higher for a person from a population in which the allele is more frequent (Figure 3.13B). Diagnostic testing for a particular genetic trait is sometimes recommended specifically to persons from those populations or ethnic groups known to have a greater prevalence of the trait. When the frequency of an allele is higher in a particular group, the probability of having an offspring homozygous for the trait is higher if both parents are from the same group than if one marries outside the group.Examples of genetic testing for recessive alleles because of withingroup risk are the following.Many African Americans now seek testing to see whether they carry a sickle-cell allele because the frequency of sickle-cell anemia is higher among African Americans (see Chapter 7, pp. 228–231).People of Mediterranean or southeast Asian descent may seek testing to see whether they carry an allele for thalassemia (see Chapter 7, p. 232) because the frequency of this disorder is higher in these groups.Ashkenazi Jews (those of eastern European descent) commonly seek testing for the recessive allele that causes Tay–Sachs disease, a fatal disorder of brain chemistry, because the frequency of the disease is higher in their group.People of western European (especially Irish) descent may seek testing for mutations in the membrane transporter gene responsible for cystic fibrosis because the frequency of the disease is higher in this group.Each of these four diseases is a single-gene trait with recessive inheritance. There may be more than one defective allele for a disease and a range of disease severity depending on the exact mutation in the allele; cystic fibrosis is an example. Therefore, determining by genetic testing that a person is homozygous recessive most often does not tell you the severity of future disease, or even whether disease will actually develop.People outside any higher-risk group can also inherit each of these diseases but their probability of doing so is lower simply because the frequency of the recessive allele is lower in their groups. These traits are rare even in the higher-risk groups where they are ‘more frequent,’ far more rare than the 1% shown in Figure 3.13B. Therefore most people, even those in a higher-risk group, are not heterozygous carriers of these rare recessive traits. (The frequency of heterozygous carriers can be calculated from the frequency of the recessive trait by a method we discuss in Chapter 7, pp. 222–223.)Genetic testing of this sort should be done only on a voluntary, informed-consent basis and, in general, only when it is of potential benefit to those being tested or to their children. Community leaders of various ethnic groups, including many clergy, have helped to organize genetic testing programs and have encouraged people to participate.Using information from genetic tests. When a genotype for a disease is detected, the decision about what to do is left up to the person, or to his or her parents if the person is a child. A patient’s decision should be based on a clear knowledge of the possible choices, their consequences, and the extent to which an outcome can or cannot be predicted by the test. Genetic counselors help people to understand these choices, but the code of ethical conduct of genetic counselors prohibits them from making a decision on behalf of their clients: clients could rightfully resent any counselor who has pressured them into a decision.Some decisions that must be made after genetic testing are difficult for the people making them. Couples who know they are at risk of bearing children with a genetic disease may decide to adopt children instead. In other cases, knowledge of a genetic condition permits medical intervention at the earliest possible stages, when chances of successful treatment may be better. For conditions that cannot be treated, some couples may choose to abort the fetus bearing the genetic defect. However, people committed to a pro-life position believe that the potential benefits to those being tested or to any future children can never justify what they view as the murder of a fetus.Genetic testing has already led to some highly inventive mixtures of tradition and modern technology. The Hasidic Jews of Brooklyn, New York, who are mostly descended from the Ashkenazi Jews of Eastern Europe, have a relatively high population frequency of the gene for Tay–Sachs disease. Marriages are traditionally arranged within the Hasidic community, and marriages outside the community are rare; this pattern generally increases the rate at which recessive alleles come together and produce recessive phenotypes. Because they are ethically opposed to all abortions, the Hasidim do not permit genetic testing in utero. The availability of a test that detects Tay–Sachs heterozygotes has, howeveever, allowed the Hasidic community to set up a computerized registry under their strict control. Testing of all persons within the community is encouraged, and the results are entered into the registry under a code number that guarantees confidentiality. The registry permits the traditional matchmakers to check potential couples before proposing a match; if both partners are carriers for Tay–Sachs disease, the matchmaker is warned of this fact and the match is never made. Before this registry was set up in 1984, the Kingsbrook Jewish Medical Center in Brooklyn, which serves the Hasidic community, had an average of 13 Tay–Sachs children under treatment at any one time; after just 5 years, the number of Tay–Sachs children under treatment in the hospital dropped to two or three.The ethics of genetic testing. Genetic testing is sometimes a mixed blessing. If a genetic defect can either be cured or phenotypically suppressed, or if heterozygote detection permits at-risk couples to decide against having children, then a genetic test can be justified on the grounds that it relieves future suffering. However, most genetic defects cannot be cured. What is the point of testing a person for a condition such as Huntington’s disease that can be neither controlled nor cured? One reason is that it permits people who carry a genetic condition to decide whether or not to have children. Will a person who tests positive for such a genetic disease be denied insurance or employment on the basis of the test results? Will a woman choose to abort a fetus if a genetic disease is detected in utero? Box 3.1 examines some of the ethical questions that arise in connection with various forms of prenatal and at-birth testing.Another ethical issue concerns the use of prenatal screening not for the purpose of detecting a disease-associated allele but to find outBOX 3.1 Ethical Issues in Medical Decision-making Regarding Genetic TestingShould society influence the private decisions of individuals? To what extent do (or should) financial considerations limit the choices available? Suppose a child is born with a birth defect or other congenital condition. Is it ever ethical to withhold treatment? (Similar ethical issues are raised by conditions resulting from injuries, infectious diseases, poor maternal nutrition, or other causes.) What if the same disease is diagnosed in a fetus in utero—is it ethical to abort the fetus? The decision to abort a fetus or to withhold treatment from a child with a genetic disease raises important ethical questions. Here are some questions to consider.Tay–Sachs disease is a genetically controlled disease whose victims are in constant pain and never survive beyond about 4 years of age. Does it make sense to spend thousands of dollars on the medical care of a child who has no chance of living beyond age 4, or even of enjoying those few years free from pain? Would it make a difference if a few people with the disease were capable of surviving? What if we were dealing with a disease that people could survive, but only with some disability?When genetic testing has been done, people often meet with a genetic counselor to have the results of the test explained to them. The code of ethics of genetic counselors includes the ethic that they give information about ‘health risks’ in a non-directive and ‘value-neutral’ way. Is this possible? In what ways does a person’s concepts of ‘health’ influence how they understand information about health risks?The involvement of third-party insurance policies raises more issues. Should insurance policies pay for genetic testing? Should insurance policies pay medical expenses for genetic diseases that could have been avoided after screening? Some insurance policies will pay for medical treatment, but not for the testing that might have avoided the need for the treatment. Do you think insurance policies should cover genetic screening?Should genetic screening be covered for certain ethnic groups but not others, just because the risks differ? For example, thalassemia is more prevalent among Italians, Greeks, and certain southeast Asians; should insurance cover testing for this condition in a person of Italian descent, but not in a person of English or Danish descent? Or in the instances common in the United States, in which descent is either mixed or unknown?If a genetic disease is detected during pregnancy, should insurance policies cover termination of the pregnancy if desired by the parents? If parents elect not to terminate a pregnancy, and a child is born with a genetic disease, should insurance policies cover any specialized medical care that might be necessary? Should insurance companies be allowed to deny coverage or increase premiums if a genetic disease is discovered?Screening for some inherited diseases such as PKU are done on all newborns. Informed consent is not gathered as the screening is universal and diet can prevent the harmful effects of the mutation. As tests are developed for other genetic diseases, should screening for these become routine? Do parents have the right to refuse to be told the results of such tests? What if there is no cure for the condition detected?What role might science have in answering questions of medical ethics that are related to genetics? For example, can science help in assessing the benefits and risks of genetic screening? How reliable are the genetic tests? (For example, the test to detect a cystic fibrosis allele is currently less than 90% accurate.) To what extent does the detection of an allele predict a harmful phenotype? What constitutes sufficient evidence that a condition is genetically determined? What are the limits of the ability of science to contribute answers to these questions of medical ethics? whether the fetus is a boy or a girl, something easily determined from examining the chromosomes. Will couples use this technology to select the sex of their offspring? This already happens in India, where abortion is legal and determination of the sex of the fetus by ultrasound is widely available to those who can afford (or can borrow) a fee of a few hundred dollars. A 1988 study of 8000 abortions in India’s clinics showed that 7997 were female and only 3 were male. In the United States, clinics offering prenatal genetic testing have found that over one-fourth of the couples who come to them are motivated by the possibility of choosing their baby’s sex.As genetic testing becomes more common, it is inevitable that test results will occasionally be misused. In one case, school officials were told that a child needed to be kept on a special diet because he had phenylketonuria (PKU). Although he was functioning normally, the child was placed in a class for the learning disabled. The school officials apparently knew that PKU could cause mental retardation, but were unaware that this outcome could be averted by the special diet. As this case shows, the misuse of genetic information may result from ignorance.Discrimination by employers or insurers represents another possible misuse of genetic information. Employers may refuse to hire or promote, or insurance companies may refuse to insure, persons who have or who are suspected of having a genetic condition. In some cases, benefits have been denied to heterozygous carriers of recessive conditions or to persons at risk for other reasons whose phenotype was unaffected. The practice is still uncommon, but it is growing and is likely to continue to grow as more and more genetic information becomes available through medical testing. One of the best safeguards against this kind of discrimination is a strict adherence to rules governing the confidentiality of medical records and other personal information held by health care providers and medical testing laboratories. Recent rulings state that the Americans with Disabilities Act protects people from discrimination on the basis of their genetic profile.The language used by geneticists and genetic counselors may be misleading when only those persons who are homozygous for the nondisease allele are reported as ‘normal.’ Heterozygotes are called ‘carriers’ although phenotypically they show no disease. In Figure 3.13A, for example, only the child on the far left of the diagram would be reported as normal, even though 75% of the children and both of the parents are phenotypically normal with no sign of disease.Altering individual genotypesSome rare genetic traits impair health. In the future, it may become possible to correct certain genetic defects by direct alteration of the individual genotype. A more realistic possibility is a form of gene splicing in which the functional allele is added to the DNA of persons with defective alleles, a practice commonly referred to as gene therapy. A new gene is inserted into a cell that also continues to carry the mutated allele. We will cover the details of gene therapy in the next chapter.Altering the gene pool of populationsSome people have proposed that, instead of treating people one at a time, we should alter the genetic makeup of populations (the entire gene pool) by changing the frequencies of certain genotypes. One difference between this approach and the approaches already described has to do with who is perceived to reap the benefits. Genetic testing, counseling, and the altering of individual genotypes are justified in terms of the pain and suffering that may be spared to individuals. In contrast, all attempts to alter the gene pool carry with them notions of harm or benefit to society rather than to the individual.Positive eugenics. The altering of the gene pool through selection is called eugenics, from the Greek words meaning ‘good birth.’ This idea is not at all new: Plato’s Republic (book 5) suggests that the best and healthiest individuals of both sexes be selected to be the parents of the next generation, much as we breed our horses and cattle. Plato’s type of eugenics is called positive eugenics, meaning an attempt to alter the gene pool by selectively increasing the genetic contributions of certain chosen individuals or genotypes. Positive eugenics was also proposed in the twentieth century by the Nobel Prize-winning geneticist H.J. Muller, who advocated setting up sperm banks to which selected male donors would contribute. Muller thought that women would eagerly seek artificial insemination with these sperm in the hopes of producing genetically superior children. Several entrepreneurs have established sperm banks (and a smaller number of egg banks) offering to infertile couples (and others) the gametes of people thought to carry desirable traits. The system is not regulated, however, by any public agency, and many sperm banks and egg banks seem to be motivated more by profit than by any desire to change the gene pool. In 1999, a photographer in California began advertising the eggs of several fashion models, offering them at auction to the highest bidder over the Internet.Ethical and other questions raised by positive eugenics usually center on the lack of an agreed standard for human excellence. The traits most often discussed by those who favor eugenics are intelligence and athletic ability. However, these traits are genetically complex and are highly influenced by education, training, and other environmental variables. Studies attempting to demonstrate a genetic influence on these and other traits were in many cases poorly done, leading many scientists to doubt the existence of any reliable evidence concerning the genetic control of human intelligence and other complex traits.The complexity of the human genotype raises other issues. What if Einstein had been heterozygous for some genetic disease? If a society wanted to use his germ cells to breed people of superior intelligence, they would also unwittingly be selecting whatever other traits he happened to possess, possibly including a genetic defect in the process. Suppose a person inherited the manic-depressive disorder of Robert Schumann or Vincent Van Gogh, instead of their creative talents? What liability or what responsibility would a sperm bank face if a descendant were born with a genetic defect? What constitutes ‘superiority’ in an individual, and who should have the power to make such choices?Negative eugenics. Most discussions of eugenics have centered on negative eugenics, the prevention of reproduction among people thought to be genetically defective or inferior. Founded by Francis Galton (1822–1911), a cousin of Charles Darwin, the modern eugenics movement has generally tended to emphasize negative measures. Galton and his supporters were very much interested in measuring intelligence, and they developed some of the early versions of what we now call IQ tests. Through the use of these and other tests, supporters of eugenics have long sought scientific respectability for their attempts to label certain people as genetically defective or inferior.The Nazis instituted a program of negative eugenics in Germany, beginning with the forced sterilization of mental ‘defectives,’ deaf people, homosexuals, and others. The eugenics program soon grew into a program for the mass killing of all those millions who did not belong to Hitler’s ‘master race.’ By 1945, the Nazis had killed millions in the name of racial purity and Aryan superiority. The Nazis also practised positive eugenics by encouraging German women with certain traits to have more children.In the United States, the eugenics movement started as a series of attempts to identify, segregate, and sterilize mental ‘defectives.’ The movement soon found allies among racists and especially among those who sought to curb the new waves of immigration during the period from about 1890 to 1920. During the 1890s, one Kansas doctor sterilized 44 boys and 14 girls at the Kansas State Home for the Feeble-Minded, while Connecticut passed a law prohibiting marriage or sexual relations between any two people ‘either of whom is epileptic, or imbecile, or feeble-minded.’ A 1907 Indiana law required the sterilization of ‘confessed criminals, idiots, imbeciles, and rapists in state institutions when recommended by a board of experts.’ Fifteen other states passed similar laws, as often for punitive as for eugenic reasons. From 1909 to 1929, 6255 people were sterilized under such laws in California alone.The writings of the American eugenicists became increasingly racist and anti-immigrationist in tone during this period. One eugenicist, for example, wrote in 1910 that “the same arguments which induce us to segregate criminals and feebleminded and thus prevent breeding apply to excluding from our borders individuals whose multiplying here is likely to lower the average [intelligence] of our people.” In the 1960s, H.J. Muller wrote several articles warning against the practice of protecting and extending the lives of the ‘genetically unfit,’ those whom natural selection would tend to eliminate from the population. According to Muller, our medical intervention would only perpetuate genetic defects in our gene pool. Muller spoke pessimistically of a population divided into two groups, one so enfeebled from genetic defects that their very lives had to be sustained by extraordinary means, and the other group consisting of phenotypically normal people who had to devote their entire lives to the care and sustenance of the first group. Muller’s views have not been substantiated by any evidence.Biological objections to eugenics. Biological arguments against negative eugenics are based on the realization that eugenic measures could be expected to produce only small changes at great cost. Most known genetic defects are both rare and recessive, and selection against rare, recessive traits can only proceed very slowly no matter what the circumstances. As the trait gets increasingly rare, selection against it becomes increasingly ineffective. For example, the gene for albinism has a frequency of about 1 in 2000 in many human populations. If a eugenic dictator ordered all albinos to be killed or sterilized, theoretical calculations show that it would require about 2000 generations (about 50,000 years) of constant vigilance just to reduce the frequency of this trait to half of its present value. The reason why the process works so slowly is that most individuals carrying the gene for a rare, recessive trait are heterozygous and their phenotype does not reveal the presence of the gene. In contrast, modern techniques that allow the detection of the gene in heterozygous form would greatly increase the effectiveness (and hence the dangers) of negative eugenic measures.For characteristics such as height or IQ, which are controlled by many genes and are influenced strongly by environmental factors, estimates are that eugenic selection would be so slow as to be barely perceptible. One geneticist calculated that it would take about 400 years of constant, unrelenting and totally efficient selection to raise IQs by about 4 points; the same improvement could be achieved through education in as little as 4 years, and with far less cost. This topic is addressed in more detail in Chapter 7.Finally, eugenic measures can at best address only a small percentage of undesirable conditions, because most physical disabilities and medical conditions result from accidents, from infectious illnesses, or from exposure to toxic substances in the environment, not from inherited genetic makeup, and eugenic measures are powerless to alter these nongenetic causes. Genetic conditions may also result from new mutations, rather than from the inheritance of defective genes, and eugenic measures have no capacity to eliminate newly mutated genes or to depress the frequency of any gene below the mutation rate.There is no biological basis for the claims of any eugenics movement that their methods could in any way improve humankind other than at great cost. The risks of negative eugenics are especially great, and include the possibility of genocide—the attempted extermination of a race or ethnic group. In addition there are no biological benefits. We are coming to know that population health and stability depends on genetic diversity; thus, narrowing a gene pool eugenically makes the population more vulnerable to infectious disease. Infectious disease is a far more widespread and common cause of sickness and death than is genetic disease.Changing the balance between genetic and environmental factorsAlthough many traits are inherited, most are also influenced by the environment. Phenotypes result not just from genes but from the interactions between genes and their environment. In addition, far more disability is caused entirely environmentally through accidents and illnesses than is caused genetically. Even for most conditions that are caused genetically, elimination of an allele from the population is hardly the only option. Most genetic conditions can be modified or accommodated in several different ways.Euphenics. Euphenics (literally, ‘good appearance’) includes all those techniques that either modify genetic expression or alter the phenotype to produce a modified phenotype. Plastic surgery, such as to repair body parts, is a form of medical intervention that alters the phenotype. Other examples include the installation of pacemakers in defective hearts, the giving of insulin to diabetics, and the dietary control of phenylketonuria. Although the genes remain unchanged, euphenics modifies or compensates for their phenotypic expression is in such a way that they no longer cause harm.Many leading geneticists have argued, as an alternative to eugenics, that there is nothing wrong with altering the phenotype or the environment so that formerly disabling genotypes are no longer so harmful or debilitating. A leading advocate of this viewpoint was Theodosius Dobzhansky (1893–1975), who favored measures to permit people with hereditary ‘defects’ to overcome their handicaps and become phenotypic copies (phenocopies) of normal, healthy human beings. Once phenotypes could be controlled culturally, said Dobzhansky, the presence of formerly defective genotypes would cease to be the subject of any great concern. Euphenic intervention is already common practice for a number of genetic conditions. As our ability to modify phenotypes increases (e.g., with advances in corrective surgery), this type of practice is likely to become more common.Euthenics. Another type of intervention is called euthenics. In this form of intervention, both genotype and phenotype remain unchanged, but the environment is modified or manipulated so that the phenotype is no longer as disabling as before. (In euphenics, by contrast, the phenotype is modified.) Examples of euthenic measures include canes, crutches, wheelchairs, and wheelchair ramps for those who cannot walk unaided, guide dogs and Braille for the sight-impaired, eyeglasses for the nearsighted, and so on. Conditions that are improved or assisted by euthenics may be either genetic or not.Most people with disabilities support research that would prevent the recurrence of their condition in other people, especially if pain or paralysis are involved. However, medical research is expensive, its results are uncertain, and its benefits may take many years to become widely available. Euthenic measures are often less expensive and more quickly made available once they have been developed. Many of the people who use euthenic devices feel that they would be better served by simple improvements in the devices (e.g., better wheelchairs) than they would be if medical research were our only emphasis.Eupsychics. Many people with uncommon traits or conditions (whether genetic or not) feel that they are best served by being accepted as they are and do not necessarily want to be ‘cured.’ (For an example, see our Web site, under Resources: Deafness.) Social and behavioral measures, or eupsychics, may lessen the impact of or compensate for disabling conditions. Included are the special education of handicapped individuals, mainstreaming (education of the handicapped in a regular public school setting), and the education and social conditioning of nonhandicapped members of society so that they will better understand and accommodate the needs of all citizens.Genetic research seeks to understand the molecular mechanisms underlying normal physiology and health, but genetic testing and counseling emphasize diseases. The assumptions underlying genetic testing have at times included viewing variations as defects and desiring to apply to humans some arbitrary standard of perfection. Society may be better served by an emphasis on the abilities, rather than the disabilities, of each individual. All individuals should be encouraged to develop their talents and abilities to the fullest. Whenever a person is discouraged from trying to develop a certain skill, ability, or talent, both the individual and the society are the losers in the long run.Are all ‘birth defects’ genetic defects? Do the same ethical questions regarding diagnosis and counseling apply to both genetic and nongenetic traits?In some hospitals, screening for phenylketonuria is often performed on all infants. Does this violate the principle of informed consent? Is this practice ethical or not? How is it commonly justified? Do you feel that the justification is adequate?Some groups opposed to abortions have also begun to object to certain kinds ofgenetic testing. What good, they ask, can come from knowing that a fetus suffers from a particular genetic or chromosomal defect if the parents are opposed to abortion of the fetus on religious or similar grounds? For such situations, discuss the costs, benefits, and ethical status of genetic testing. Does it matter what kind of testing is performed? Does it matter what genetic or chromosomal defect is being tested for?Do unborn children have a ‘right’ to inherit an unmanipulated set of genes? Do they have a right to inherit ‘corrected’ genes if such a possibility exists? What kind ofTHOUGHT QUESTIONSinformed consent can we expect on behalf of unborn generations? Can a person make decisions that affect the genotype of all of his or her progeny? Do we need safeguards to protect future generations against the selfish interests of the present generation?In what sense is ‘positive’ eugenics positive? In what sense is it negative? Should human populations be bred as we breed domesticated animals?If public funds will be spent for the care and treatment of a person with a genetic condition, does that alter the ethical balance between the rights of the individual and the rights of society? If a euphenic measure is available, should public funds be used to ‘correct’ the condition? Should the person have the right to refuse such treatment? Should public funds be withheld from a person who refuses such euphenic measures?How much access to genetic information about a subscriber or employee should aninsurance company or an employer have? How much access do they have now?Concluding RemarksThrough the processes of transcription and translation, genes get expressed as proteins, and proteins lead ultimately to phenotypes. As we have seen in many contexts in this chapter, however, most of human genetics is more complex than the either/or traits that Mendel studied in pea plants. It is not that Mendel’s laws do not apply to humans; they do. There are some human conditions that do follow simple Mendelian inheritance with a mutation in a single gene leading to the trait. Rather, since Mendel’s time, we have learned that the inheritance of most traits in all organisms, not just in humans, is more complex than Mendel and scientists early in the twentieth century envisioned. Many traits, including sex determination and disease susceptibility, are influenced by multiple genes. The expression of the genotype as a phenotype is also influenced by the environment. Most biologists today would agree that phenotypes are far more malleable than was assumed in the past, contradicting earlier ideas of biological determinism that assumed that genotypes solely determined phenotypes. In addition, phenotypes can be modified by technologies and other aspects of cultures.We are entering an era in which people will be able to find out a lot about their own genotype and the genotypes of their children. Identifying a genetic predisposition to a chronic disease may allow a person to make healthier choices about his or her diet and lifestyle. As we saw with the couple in the introduction to this chapter, people will have the power to find out whether a fetus carries a genotype for a fatal illness. This new knowledge will give people choices that they have not had in the past, but none of those choices are likely to be easy.Chapter SummaryDNA, a nucleic acid, is the template for the synthesis of another nucleic acid, RNA, in a process called transcription.mRNA is the template for protein synthesis in a process called translation. Three mRNA bases form a codon, directing the addition of one amino acid to a protein.Changes in the DNA sequence (mutations) are reflected as changes in the mRNA sequence that usually result in changes in the amino acid sequence of proteins. Such changes may affect the folded shape and therefore the function of the proteins. Gene mutations create new alleles.Phenotypes result from the activity of proteins, often of several proteins acting together.Human genes are now being identified at an increasingly rapid pace through pedigrees and linkage with DNA markers.Many genetic diseases result from alleles that code for nonfunctional proteins. Some of these are inherited as simple Mendelian alleles; others show more complex patterns of inheritance.Risk is the probability of a condition’s occurring; some genotypes are associated with increased risk.Genetic diseases can be diagnosed prenatally by amniocentesis, by chorionic villus sampling, and by other techniques, including those that use the polymerase chain reaction (PCR) to amplify DNA sequences into many copies. Testing for genetic diseases can also be done on children or adults. In any case, testing requires prior informed consent.Altering the gene pool at the population level is called eugenics.CONNECTIONS TO OTHER CHAPTERSChapter 1 Molecular genetics is forcing a change in the scientific paradigm that includes our concepts of phenotypes and traits.Chapter 1 Manipulating human heredity has raised several ethical concerns.Chapter 2 The same basic laws of genetics apply to humans as to other animals and to plants.Chapter 4 Human genes are often very similar to those from other species, and studying these relationships can tell us about species’ evolutionary history.Chapter 5 Evolution takes place whenever allelic frequencies change.Chapter 7 Human populations differ in the frequencies of many alleles.Chapter 8 Mating patterns and sexual strategies can alter allelic frequencies in populations.Chapter 9 Population control seeks to manage the size of populations; eugenics, in contrast, seeks to alter the gene pool.Chapter 11 Genetic engineering can be used to improve the traits of commercially important plant species.Chapter 12 Predispositions for some cancers are hereditary.Chapter 13 Huntington’s disease is one of several brain disorders for which a genetic basis has been identified.Chapter 18 Conserving genetic diversity is an important aspect of protecting biodiversity.PRACTICE QUESTIONSWhen a man and a woman who are both albino have children, what percentage of their children will be albino?Are DNA markers genes?A particular disease is suspected of being a genetic disease. A person with the disease tests positive for 15 DNA markers, each detected with a specific DNA probe, and negative for 20 other markers. What would be the next step in trying to determine which of the markers might be located near a gene responsible for the disease?What is the risk of a child’s having a recessive genetic trait when both parents are from a population in which the frequency of the recessive allele is 1 in 1000 (0.1%)? What is the risk when one parent is from a population with an allelicfrequency of 0.1% and the other parent is from one in which the frequency is 1 in 100,000 (0.001%)?How many copies of a DNA fragment are synthesized in 20 rounds of amplification by PCR (assuming that each step works correctly)? How many will be synthesized in 30 rounds?How many different genes are mutated in cystic fibrosis? Do all people with cystic fibrosis have the same mutation?A point mutation that substitutes a single base for another changes that codon but not the succeeding ones. If two bases that are next to each other are replaced by two different bases, how many codons will be altered? On what might your answer depend?Taylor & FrancisTaylor & Francis GroupIssuesDoes genetic engineering fundamentally change the biology of an organism?Does gene therapy work?When should gene therapy be used? When should it not be used?Do DNA tests positively identify individuals?Why does the U.S. government fund the Human Genome Project?What benefits have been derived from the Human Genome Project?How could the results of the Human Genome Project be misused? How can we guard against such misuse?Biotechnology (The Human Genome Project; genetic engineering)Molecular biology (genomics; bioinformatics)Structure–function relationships (proteomics)4Chapter OutlineGenetic Engineering Changes the Way That Genes Are TransferredMethods of genetic engineering Genetically engineered insulin Gene therapyMolecular Techniques Have Led to New Uses for Genetic InformationThe first DNA marker: restriction-fragment length polymorphismsUsing DNA markers to identify individuals Using DNA testing in historical controversiesThe Human Genome Project Has Changed BiologySequencing the human genome The human genome draft sequence Mapping the human genomeSome ethical and legal issuesGenomics Is a New Field of Biology Developed as a Result of the Human Genome ProjectBioinformatics Comparative genomics Functional genomics Proteomics95Genetic Engineering and Genomicss a result of information published in 2001, humans now know more about themselves, at least at the molecular level, than they ever havebefore. This watershed date marked the publication of the draft of the nucleotide sequence of all of the DNA in human chromosomes. Along the way, a complete map of the location of these nucleotide sequences on the chromosomes was also produced. All of this information is stored in an enormous database that is publicly available for use by any scientist in the world. A tremendous amount of basic molecular biology has been discovered in the course of the Human Genome Project that produced this database. As a tool for biological research, this database potentially offers new ways of studying everything else in biology. In addition, the project has spawned many practical advances in biotechnology and genetic engineering.Genetic Engineering Changes the Way That Genes Are TransferredGenetic engineering is the direct alteration of individual genotypes. It is also called recombinant DNA technology or gene splicing, terms which are used interchangeably. Human genes can be inserted into human cells for therapeutic purposes (gene therapy, p. 100). In addition, because all species carry their genetic information in DNA and use the same genetic code, genes can be moved from one species to another. The uses of genetic engineering in plants are discussed in Chapter 11. Here we see some of the applications of genetic engineering for human medicine.Methods of genetic engineeringWhether the ‘engineered’ gene is one from the same species or a different species, the techniques are much the same. All these technologies depend on being able to cut and reassemble the genetic material in predictable ways. This is possible owing to the discovery of special enzymes called restriction enzymes.Restriction enzymes. Restriction enzymes are enzymes used to cut DNA at specific sites. There are several hundred restriction enzymes currently known and each cuts DNA at a different nucleotide sequence; these target sites are generally about four to eight nucleotides long (Figure 4.1). Each of these restriction enzymes is a normal product of a particular bacterial species, and most are named after the bacteria from which they are derived. Thus, in Figure 4.1, HaeIII is an enzyme from the bacteria Haemophilus aegypticus and EcoRI is from Escherichia coli. They are called restriction enzymes because their normal function within the bacteria is to restrict the uptake of DNA from another bacterial species. Each species’ restriction enzyme cuts the DNA from other species, but not its own, because its own DNA does not contain the96 nucleotide sequence that is the target site for its own enzyme.Several other enzymes are known that can break apart a DNA molecule, but an enzyme that acts indiscriminately is of little use in genetic engineering. Restriction enzymes act specifically. Each restriction enzyme generally cuts a sample of DNA in several places, wherever the DNA contains a particular sequence of bases that the enzyme recognizes, forming a series of pieces (called restriction fragments). A given restriction enzyme mixed with the same sequence of DNA always produces the same number of fragments. The length of the pieces may vary if there are variable repeat sequences, for example, but the number of pieces and the places cut are always the same. Before the discovery of restriction enzymes, breaking chromosomal DNA into pieces was done mechanically, producing different numbers of pieces every time the procedure was done, making the results of DNA techniques impossible to reproduce from one experiment to the next. Because restriction enzymes always cut at the same sites, they can be used in genetic engineering.Restriction enzymes in genetic engineering. The first step in inserting a gene for genetic engineering is to isolate the gene in question. This is carried out by using a restriction enzyme to snip out the desired segment of DNA. Each restriction enzyme cuts the DNA at specific places, defined by their DNA sequences. The most useful restriction enzymes are those that cut the two DNA strands at locations that are not directly across from each other, producing short sequences of single-stranded DNA known as sticky ends (see Figure 4.1). For example, the commonly used restriction enzyme EcoRI always targets the sequence GAATTC, cutting it between G and AATTC, breaking the two-stranded sequence into fragments that have sticky ends. The ends are called ‘sticky’ because they can stick together spontaneously with another molecule containing complementary sticky ends. In fragments cut with EcoRI, the single-stranded AATT sequences can pair with one another, stick together, and then be joined permanently. (An enzyme such as HaeIII that cuts at sites directly across from each other forms ‘blunt’, rather than sticky, ends, as shown in Figure 4.1.)If a particular restriction enzyme produces sticky ends, all fragments cut with that enzyme will have sticky ends that match one another. Thus, a fragment can be joined to any other fragment cut with the same enzyme. This makes it possible to use restriction enzymes to cut a DNA sequence and insert a functional gene with matching sticky ends.double-stranded DNAsugar–phosphate backboneHaeIII +EcoRI+Restriction enzymes that produce blunt ends are useful in other ways, but are not useful for genetic engineering because the fragments cannot be put back together.Cutting an entire chromosome with a restriction enzyme produces many fragments, only one of which contains the gene to be isolated. A DNA probe specific for the gene will isolate the fragment containing the gene of interest. As we have seen before, such a probe is a complementary DNA strand that carries a radioactive or chemical tag. The probe allows geneticists to isolate the labeled sequences, and then separate the desired genes from the DNA probes that pair with them.A functional gene isolated in this way can then be inserted into another piece of DNA. The target DNA is cut with the same restriction enzyme, so sticky ends complementary to the fragment are available, and the gene can be incorporated permanently. So far, most genetic engineering of human genes has involved the introduction of these human genes into bacteria. The reasons for this are largely practical: many human gene products are useful in medicine but are more readily produced in large amounts inside genetically engineered bacteria than inside people. For example, the hormone somatostatin, also called growth hormone, is highly valued for the treatment of certain types of dwarfism. The hormone is, however, difficult to obtain from human sources (the traditional way is to extract it from the pituitary glands of dozens of cadavers) and is therefore very expensive. Insulin, the hormone needed by diabetics, is another example of a human gene product. Both of these hormones could be obtained from sheep or pigs or other animals, but the animal hormones are not as active in humans as the human hormones, and some patients are allergic to hormones obtained from other species. Genetic engineering provides a cost-effective way of manufacturing large amounts of these human hormones in bacteria.Genetically engineered insulinHuman insulin was the first commercially produced genetically engineered product. The initial step is to grow human cells in tissue culture. Tissue culture is a procedure in which cells that have been removed from an organism are grown in a dish of nutrient-rich medium kept at body temperature in an incubator. After a sufficient number of cells have grown, DNA extracted from the cell nuclei is then exposed to a restriction enzyme that cuts the DNA into desired fragments. One fragment contains the human gene for insulin, which can be isolated using a DNA probe.The same restriction enzyme is used on nonchromosomal DNA molecules, called plasmids. Bacteria have a single chromosome in the form of a closed loop. Many also have a number of plasmids, short circular DNA pieces that are separate from the bacterial chromosome (Figure 4.2). Plasmids are used in genetic engineering because, being short, they have fewer sites at which a given restriction enzyme can cut. Cutting a DNA sequence in the plasmid with the same restriction enzyme that was used on the human DNA creates sticky ends that match the DNA fragment taken from the human cell. This allows incorporation of the human gene for insulin into the bacterial plasmid. The bacteria are then treated so that they take up the engineered plasmid. In most cases, the plasmid also contains another DNA sequence that can be used toselect the bacteria that have incorporated an engineered plasmid. For example, the plasmid might contain the gene for an enzyme that gives the bacteria resistance to a common antibiotic; the antibiotic can then be used to select the bacteria that have incorporated this gene while killing the majority that are still susceptible. The procedures sound easy and straightforward, but each step of the process is technically difficult and only a small proportion of the attempts succeed.The genetically altered bacterium can now be cloned, that is, allowed to multiply asexually, which produces vast numbers of genetically identical copies of itself and its engineered plasmid. The resultant bacteria then transcribe and translate the human gene to produce human insulin (Figure 4.3). The human insulin extracted from these bacteria, called recombinant human insulin, can be given to diabetic patients.Figure 4.3Production of genetically engineered insulin.Isolate human cells and grow in tissue culture.Isolate DNA from the human cells.Use a restriction enzyme to cut DNA into fragments with sticky ends. Isolate the fragment containing ‘insulin gene’4 Meanwhile, isolate plasmid DNA from a bacterium.Combine plasmid and human DNA; some of the plasmids will recombine with the human DNA fragment containing the insulin gene.5 Use the same restriction enzyme to cut the plasmid DNA, creating matching sticky ends.etc.7 Allow new bacteria to incorporate the recombinant plasmid into the bacterial cell, then screen bacteria to find the ones that have incorporated the human gene for insulin.8 Grow trillions of new insulinproducing bacteria.Gene therapyInstead of growing human insulin in bacteria (see Figure 4.3), genetic engineering could theoretically be used to introduce the insulin gene into human cells that do not possess a functional copy. (That would still not cure diabetes unless these cells were also capable of appropriately increasing or decreasing their output of insulin according to conditions.) This type of genetic engineering is called gene therapy, the introduction of genetically engineered cells into an individual for therapeutic purposes.Treatment for hereditary immune deficiency. Human gene therapy has been used successfully to treat severe combined immune deficiency syndrome (SCIDS), a severe and usually fatal disease in which a child is born without a functional immune system. Unable to fight infections, these children will die from the slightest minor childhood disease unless they are raised in total isolation: the ‘boy [or girl] in a bubble’ treatment. The enzyme that controls one form of SCIDS has been identified; it is called adenosine deaminase (ADA) and its gene is located on chromosome 20. A rare homozygous recessive condition results in a deficiency of this enzyme, which in turn causes the disease.Gene therapy for this condition consists of the following procedural steps, shown in Figure 4.4.Normal human cells are isolated. The cells most often used are T lymphocytes, a type of blood cell that is easy to obtain from blood and easy to grow in tissue culture.The isolated cells are grown in tissue culture.The DNA from these cells is isolated.A restriction enzyme is used to cut the DNA into fragments with sticky ends; one will contain the functional gene for ADA. A probe with a complementary DNA sequence is then used to isolate and identify the fragments bearing the gene.The same restriction enzyme is used to create matching sticky ends in viral DNA isolated from a virus known as LASN. This virus was chosen because it can be used as a vector: it can transfer the gene into the desired human cells—the host. (Other vector viruses have also been used; each virus type varies in the size of DNA fragment that can be inserted and the type of cell that it can enter.)The viral DNA is then mixed with the human DNA fragments and allowed to combine with them.The virus is allowed to reassemble itself; it is then ready for further use.Blood is drawn from the patient to be treated and T lymphocytes are isolated from this blood. These lymphocytes, like all of the other cells from this person, are ADA-deficient because they do not possess a functional ADA allele.The virus is now used as a vector to transfer the functional gene. The virus must get the gene not only into the lymphocyte but also into its nucleus. The gene must incorporate into the cell’s DNA in a location where it will be transcribed and where it does not break up some other necessary gene sequence.The lymphocytes are tested to see which ones are able to produce a functional ADA enzyme, showing that they have successfully incorporated the functional ADA allele.The genetically engineered lymphocytes are injected into the patient, where they are expected to outgrow the genetically defective lymphocytes because the ADA-deficient cells do not divide as fast as cells with the ADA enzyme.Figure 4.4An example of gene therapy showing the transfer of the human gene responsible for adenosine deaminase (ADA).Isolate normal human T lymphocytes.Grow lymphocytes in tissue culture.Isolate DNA from some of the cells.Also isolate DNA from the LASN virus and cut with the same restriction enzyme.Use a restriction enzyme to cut this DNA and produce ‘sticky ends’, then isolate fragment containing the gene for ADA enzyme.Mix the DNA fragments.Allow new virus particles to incorporate the recombinant DNA.Withdraw blood and isolate T lymphocytes from a patient whose DNA lacks the gene for ADA.Combine T lymphocytes with LASN virus (vector).Grow cells and test for the ADA enzyme, thus selecting lymphocytes that have incorporated the vector carrying this gene.11 Inject genetically engineered lymphocytes with gene for ADA enzyme into the patient.Technical difficulties in gene therapy are numerous. Transferring large pieces of DNA into cells is difficult (most genes are large). Inserting a gene in a location in the DNA where its protein product will be transcribed and translated in a normal way is far more difficult.The gene therapy described above provides a functional gene that is transcribed and translated by the body cells, producing the missing enzyme in lymphocytes. Because lymphocytes are not the only cells that need the ADA enzyme, the patient must also receive injections of the ADA enzyme coupled to a molecule that permits it to enter cells. (This last step might not be necessary for the treatment of other enzyme defects.) The enzyme controls the symptoms of the disease, but it is not a cure because the underlying disease is still present. Gene therapy for ADA was first successfully used on a 4-year-old girl in 1990. A second patient, a 9-year-old girl, began receiving treatments in 1991. Both patients are being closely monitored, and their immune systems are now working properly. However, because the genetically engineered cells are mature lymphocytes, which have only a limited lifetime, repeated injections of genetically engineered cells are needed.To get around this problem, in the hope of bringing about a morelasting cure, some Italian researchers have tried using both genetically engineered lymphocytes (as described above) and genetically engineered bone marrow stem cells. Stem cells divide to form all the developed types of blood cells (see Chapter 12) and they maintain this ability throughout life. Therefore, after repaired lymphocytes die off, stem cells with repaired DNA could divide to provide new, ADA-functional lymphocytes, possibly for the lifetime of the individual. This type of therapy was begun on a 5-year-old boy in 1992, and since then several other children have received this treatment.Questions of safety and ethics. There are legitimate safety concerns with human gene therapy. For example, any virus used as a vector must be capable of entering human cells. Might such a virus cause a disease of its own? To preclude this possibility, the viruses used in human gene therapy have been from viral strains with genetic defects that render them incapable of reproducing and spreading to other cells. Might random insertion into the host DNA destroy some other gene? Methods are being developed for directing the insertion location, but it is still largely a random event. In 1999, gene therapy clinical trials were halted in the United States when an 18-year-old boy died after receiving a viral vector for gene therapy for a metabolic disease. The reasons for his death were not apparent, so clinical studies were halted until issues of safety could be addressed. The boy’s father has testified at a U.S. Senate hearing that the boy and his family were not fully informed of the dangers of the experiment. Others have raised ethical objections to the use of the term ‘gene therapy’ in clinical trials when most of the experiments that have been done so far have not been designed to cure any condition, only to alleviate symptoms (or to test the safety of the procedure itself).Gene therapy also raises other ethical concerns. New recombinantDNA procedures are very expensive to develop. This raises ethical issues of fairness: will the benefits of genetic engineering be available only to those who can afford them? Should government programs provide them through Medicare and Medicaid? Should insurance cover their use? How can society’s health care resources best be distributed? If medical resources are limited, should an expensive procedure used on one person take up needed resources that could cover inexpensive treatments of other diseases for many people? These particular questions are not unique to genetic engineering; they apply to any expensive form of medical treatment.Genetic engineering may someday become commonplace in human cells. In theory, gene therapy could be practised either on somatic cells or on gametes. If it were performed on somatic cells, the effects of the gene therapy would last as much as a lifetime, but no longer. For example, insertion of the functional allele for insulin into the pancreatic cells of patients with diabetes might cure them of the disease, but they would still pass on the defective alleles to their children. A general consensus has been reached that using gene therapy on somatic cells has an ethical value if it is used for the purpose of treating a serious disease.If successful gene therapy is performed on germ cells, then the genetic defect will be cured in the future generations derived from those germ cells. In addition to all the ethical questions raised earlier, gene therapy on germ cells raises many additional ethical questions. Most medical ethicists today advise caution and waiting in the case of germcell gene therapy on humans until we have more experience with gene therapy on somatic cells or in other species.The use of growth hormone for the treatment of shortness (not dwarfism) in otherwise healthy children is controversial, but its testing for this purpose was approved in 1993 by the Food and Drug Administration. When does a phenotypic condition unwanted by its bearer become a disease to be treated? Who decides?Should the use of human growth factor produced by engineered bacteria to increase someone’s height be allowed? Is this simply another form of cosmetic surgery, similar to breast implantsor face-lifts?If a person dissatisfied with his or her phenotype suffers from lack of self-esteem on that account, does the lack of self-THOUGHT QUESTIONSesteem justify a procedure to correct the phenotype? (This same argument is raised to justify traditional forms of cosmetic surgery.) Do parents have the right to anticipate for a child what the future effects on self-esteem will be with and without corrective procedures? For a phenotype such as height that develops over a period of years, at what age is it appropriate (if ever) to evaluate the phenotype and decide upon corrective measures?A procedure such as gene therapy is expensive. Who should pay for it? Is gene therapy a limited resource? Does giving gene therapy to one patient thereby deprive another of medical care?Molecular Techniques Have Led to New Uses for Genetic InformationMolecular biology is an interdisciplinary field that focuses on DNA. Although there are many other kinds of molecules, molecular biologists are concerned mostly with DNA. Molecular biology techniques can tell us a lot about human genetics, and several marker systems have now been discovered for studying human DNA. The first of these marker systems, restriction-fragment length polymorphisms, is described here. More recently other markers, with names such as expressed sequence tags, microsatellites, and single-nucleotide polymorphisms, have been discovered.Each person has a unique DNA sequence. If it were practical to sequence a person’s whole genome, his or her DNA could definitively identify a person. The human genome is far too long for it to be useful for such identification, but the DNA marker techniques that have been so useful in mapping gene regions have also proved useful in distinguishing, with a high probability, any person from another except for identical twins. Two frequent uses of this technique are in the identification of suspects in police investigations and in disputes over paternity.The first DNA marker: restriction-fragment length polymorphismsIn 1980 a new mapping technique was devised that could readily be used in human studies, as well as in studies on other species. DNA contains, in addition to genes, noncoding regions that vary in length from one individual to another. Short sequences of nucleotides, 3–30 bases long, are repeated over and over anywhere from 20 to 100 times. These are called short tandem repeats. Several thousand different such repeats are now known in humans, each with a unique sequence not found elsewhere in the genome. When DNA containing variable numbers of repeats is cut with a restriction enzyme, fragments of DNA of various lengths are produced (Figure 4.5A). Variations (also called polymorphisms) in the lengths of the fragments produced with restriction enzymes are known as restriction-fragment length polymorphisms, or RFLPs (pronounced “riflips”). The fragments of different lengths are separated by a technique called electrophoresis (Figure 4.5B). As we saw in Chapter 3 (Figure 3.8, p. 73), because DNA carries an electric charge it moves in an electric field. When a DNA sample that has been cut into fragments is loaded onto a gel and electric current is applied, the fragments move. The gel material retards the movement of the fragments somewhat, and the larger the fragment, the more its movement is retarded by the gel. In the time that the electric current is on, smaller fragments will therefore move farther than large fragments. Because the nucleotide sequence of each short tandem repeat is unique, each can be detected by a specific probe, a piece of DNA with a sequence complementary to the repeat sequence (Figure 4.5C). Probes are specific and cause only those fragments to show up that have sequences complementary to the probe sequence.Molecular Techniques Have Led to New Uses for Genetic Information 105Using DNA markers to identify individualsUsing the same DNA marker techniques that we saw above, geneticists can compare DNA samples from different persons. The samples are cut with restriction enzymes. Pieces are separated according to size by electrophoresis and then transferred to a paper material. Radioactively labeled probes complementary to known DNA sequences are then used to detect the fragments containing particular variable repeats. These fragments appear as bands, with their location indicating the fragment length. Several probes can be used at once so that many bands show up, not just one or two as in the example shown in Figure 4.5, in which just one probe was used.Bands at the same position indicate fragments of the same length in samples being compared. If the band patterns are not the same, then it can be stated with certainty that two samples did not come from the same person. In the example from a criminal investigation shown in Figure 4.6, person 1 can be eliminated as a suspect because the band pattern from the evidence is not the same as that from sample 1. The reverse is not true, however; band patterns that are the same are not an absolute guarantee that the samples came from the same individual. What are being visualized are chunks of DNA of variable lengths, not the DNAFigure 4.5Restriction-fragment length polymorphisms (RFLPs).DNA from a pair of chromosomesThe pieces differ in length depending on the number of repeats that exist within a piece. In this example, the piece from the father is shorter because it has fewer repeats than the piece from the mother, which is longerbecause it has more repeats.chromosome from fatherchromosome from motherrepeat sequence restriction enzyme cut(B) SEPARATION BY ELECTROPHORESISThe mixture of pieces is placed on a gel and exposed to an electric field. Because DNA has a negative charge, the pieces move toward the positive electrode. In the time that the current is on, smaller pieces travel farther through the gel than the larger ones do. None of these pieces is visible yet.sample loaded onto gel by pipette+© DETECTION WITH A PROBENone of the pieces can be seen; however, they can be detected with a variable-repeat probe tagged radioactivelyor chemically (bands shown in color). The probe is a small piece of DNA with a sequence complementary to the sequence of that variable repeat, so the probe will bind to those pieces of DNAcontaining that variable repeat. The probe thus does two things: it identifies pieces with that specific repeat and it indicates whether the sequence is repeated a few times (to give a short DNA piece) or many times (to give a long piece). Other probes will find other sequences that are repeated in other chromosomal locations.DNA fragment not boundby the probelonger piece from mother’s chromosomeshorter piece from father’s chromosomedirection of travelFigure 4.6Forensic DNA technology. In this example, the evidence sample shows the same pattern of bands as DNA from suspect 2. There is therefore a high probability that the DNA in the evidence is from that suspect. The person from whom sample 1 was taken can be eliminated as a suspect.samples from two suspectsevidenceisolate and purify DNAdigest DNA with restriction enzymeseparate DNA fragments by electrophoresissequences of the chunks. A score is calculated that indicates how likely it is that a randomly chosen person, other than the one tested, could have the same band pattern.The likelihood that another, randomly selected person could have the same banding pattern is made very small in two ways. First, the DNA probes selected are those that pick up specific DNA markers that are rare in a given population. Also, several DNA probes are used, one after another, to produce a composite banding pattern. The probability that the bands produced with just one DNA probe are the same for two people is equal to the frequency of that DNA marker in the population. If more than one DNA probe is used, the probability of both band patterns’ matching is equal to the population frequency of the first DNA marker multiplied by the population frequency of the second, and so on for multiple DNA probes and markers.There are many ways in which the banding pattern can yield flawed or ambiguous results if samples are not properly processed. In samples from crime scenes, there is often DNA from mixed sources, including DNA from several people and from bacteria or fungi. Protein material in the sample may slow the movement of a restriction fragment in the electrophoresis, making the DNA fragment appear as though it were larger than it is. Other chemicals in the samples, such as the dyes in cloth, can interfere with the restriction enzymes cutting the DNA. However, when the tests are done properly and with the proper controls, they can be very reliable. In addition to linking suspects to material taken from crime scenes, the methods can be used to settle questions of disputed parentage. The methods can also be used to identify the dead when an intact corpse is not available, as in the aftermath of the terrorist attacks in the United States on 11 September, 2001.Using DNA testing in historical controversiesAn unusual use of this technique helped shed new light on a historical controversy involving Thomas Jefferson, the third president of transfer fragments to nylon membrane (Southern blotting)add radioactively labeled DNA probeswash membrane, expose to X-ray film, developDNA profilesE = evidence S1, S2 = samplesfrom two suspectsthe United States. DNA markers were used to investigate whether Thomas Jefferson could have been the father of children borne by one of his slaves, Sally Hemings. Two oral traditions exist: descendants of Hemings’s sons, Eston Hemings Jefferson and Thomas Woodson, believe that Jefferson was their ancestor, while descendants of Jefferson’s sister believe that one of her children, Jefferson’s nephew, fathered Sally Hemings’s later children. Researchers compared Y chromosomal DNA from descendants of two of Sally Hemings’s sons with DNA from descendants of one of Thomas Jefferson’s uncles. No Y chromosomal DNA was available from Thomas Jefferson’s direct descendants because he had no sons who survived to have children.The DNA data show that a set of 19 markers (collectively called the haplotype) is shared by all five of the descendants of Jefferson’s uncle who were tested and by the descendants of Eston Hemings Jefferson. The haplotype is not shared by descendants of Hemings’s other son, Thomas Woodson, or by the descendants of Jefferson’s nephew, nor was it found in almost 1900 unrelated men. Thus, Jefferson may definitively be ruled out as the father of Thomas Woodson.In the case of the positive match, however, the evidence supports, but does not prove, the idea that Thomas Jefferson could have been Eston Hemings Jefferson’s father. As we explained earlier, positive matches indicate probabilities, not definite identity. The researchers state that because “the frequency of the Jefferson haplotype is less than 0.1%,” their results are “at least 100 times more likely if the president was the father of Eston Hemings Jefferson than if someone unrelated was the father.” They also state that they “cannot completely rule out other explanations of our findings,” but that “in the absence of historical evidence to support such possibilities, we consider them to be unlikely.” Interestingly, although the authors are very precise in the text of their article, the title, “Jefferson fathered slave’s last child,” overstates their results (E.A. Foster et al. Nature 396: 27, 1998).Thomas Jefferson had daughters who survived to have children. Why was the DNA of their descendants not used in the study to determine the paternity of Eston Hemings Jefferson and Thomas Woodson?The authors of the Jefferson study state that they “cannot completely rule out other explanations of our findings.” What other explanations are biologically possible?THOUGHT QUESTIONSThink about the study done on DNA from descendants of Jefferson’s family and Sally Hemings’s sons. Why is the title of the study, “Jefferson fathered slave’s last child,” an overstatement of the results?In the study on Jefferson’s descendants, why did the researchers test DNA at 19 DNA marker sites, rather than just at one or two sites?The Human Genome Project Has Changed BiologyThe complete genetic material of an entire organism is known as its genome. In 1986, scientists proposed a project to make a genetic map, or catalogue, of a prototypical human, including the chromosomal location of all human genes and the complete DNA sequence of the genome. Many scientists and physicians think that many medical and other benefits could flow from knowing the location and sequence of all the genes. Such knowledge would facilitate locating genes that are associated with diseases or disease susceptibility. It will also make possible the development of drugs that are much more specifically tailored to block particular molecules. This effort became known as the Human Genome Project. The Human Genome Project was funded by the U.S. Congress to begin work in the fall of 1989, and James Watson, co-discoverer of the double-helical structure of DNA, was appointed as the first director.Watson stated his belief that the Human Genome Project would tell us what it means to be human.It should be noted, however, that although we talk of the human genome sequence, the DNA sequence of each person is unique. There is no one DNA sequence that is representative of every human, just as no one person could be said to represent all humans in any other method of describing people. It is estimated that one person differs from another in about 0.1% of the 3 billion base pairs in the human genome. People share the same genes but the nucleotide sequences of those genes vary in different alleles.Sequencing the human genomeOne of the stated goals of the Human Genome Project was to determine the human DNA sequence. When we read in the newspaper or hear on television about a genome being sequenced, what does this mean? The ‘sequence’ of DNA is the order in which the four nucleotide bases (see Chapter 2, p. 56) appear from one end of the DNA molecule to the other. Because DNA is an unbranched molecule, the sequence of bases can be ‘read’ from one end to the other.Determining the order of nucleotides by using fluorescent dyes. Because the amount of DNA in even one chromosome is enormous, it is not practical to work with the whole length of a chromosome in determining sequences. The maximum size of pieces that can be sequenced is currently about 500–700 bases long. The chromosomes are therefore separated and each is cut into overlapping pieces with restriction enzymes. Each piece is inserted into a plasmid which enters a bacterium. The bacteria then divide repeatedly and make large quantities of one piece at a time, as we saw on p. 98 for bacterial production of human insulin.The nucleotide sequence of each of the pieces can then be determined using an established method (called the di-deoxy method) based on DNA synthesis. The DNA is used as a template for synthesis of new DNA strands in a test tube, as outlined in Figure 4.7. The overall result is the production of a series of smaller pieces, each piece one nucleotide longer than the next. Each of the small pieces is then separated by electrophoresis. The pieces are made visible with a fluorescent dye, a different color used for each of the four nucleotides. Unlike the specific probes used with DNA markers, fluorescent dyes make all of the pieces visible that end in that nucleotide. The sequence of bases in the DNA fragment can thus be read from the gel: the base found at the end of the shortest piece is first (traveled farthest in the gel), followed by the base found at the end of the next longer piece (traveled the second farthest in the gel), and so forth.Mistakes can occur in either copying or sequencing, and repeating the process does not always give the same answer, so the technique must be repeated several times by different laboratories until a consensus sequence is established. After the sequence of each piece has been determined, the pieces must be arranged in their original order to get the overall sequence. Remember: this sequence analysis has been carried out on only one fragment of a chromosome at a time. The next challenge is to piece together the sequenced fragments, which is part of the mapping procedure discussed below.The non-coding DNA. Most of the human chromosomal DNA does not code for genes, however, and the Human Genome Project included thesequencing of these non-coding regions. The non-gene DNA consists of ‘spacer’ sequences that are never transcribed, and other kinds of sequences that are transcribed but never translated. The function of most of these non-gene sequences is currently unknown, and the wisdom of spending an estimated $15 billion on their sequencing is a question on which opinion, even among scientists, differs widely. These non-coding regions, however, have turned out to be the locations of many of the DNA markers discussed earlier, which have allowed us to find where specificFigure 4.7Discovering the nucleotide sequence of a piece of DNA.primer to start synthesisGCA T direction of synthesisC GTATA C AG T C AGG T Csingle-stranded DNA to be sequencednormal triphosphate precursors (A, T, C, G)+small amount of abnormal precursors(A and T and C and G)A piece of single-stranded DNA to be sequenced is added to a test tube with an enzyme to activate DNA synthesis and the four precursor triphosphates (black A, T, C and G). Also added are small amounts of chemicals similar to each of the triphosphate precursors, which can add to the growing chain but cannot then bond to the next precursor. Each of the four types of abnormal precursors is labeled with a differently colored fluorescent dye: red As, green Ts, blue Cs and orange Gs.DNA synthesis is then allowed to proceed. When a normal, black precursor is added to the template, theGCAT AGCAT ATGTCAGCAT ATGCAT ATGTGCAT ATGTCGCAT ATGTCAGTCGCAT ATGGCAT ATGTCAGchain keeps growing. When, by random chance, an abnormal precursor gets added instead, synthesis of that chainGCAT ATGTCAGTCCA GCAT ATGTCAGT GCAT ATGTCAGTCCGCAT ATGTCAGTCCAG stops, leaving a strand shorter than thestrand being sequenced. Each chain isone nucleotide longer or shorter than the others. Each short sequence ends with a fluorescently tagged molecule.direction in which DNA moves during electrophoresisThe pieces can then be separated by size using electrophoresis. In the time that the current is on, the fragment that consists of the primer plus a single nucleotide (A in this illustration) will travel the farthest. The fragment that is the primer plus two nucleotides (A + T) will travel not quite as far, and so forth.A T G T C A G T C C A Gsequence of newly synthesized DNAREADING THE SEQUENCEA fluorescence detector reads each band of the gel, detecting the color of the dye labeling that band. distance from bottom of the electrophoresis gel genes are located. Other scientists suggest that these non-coding regions will also turn out to be important for other reasons. For example, the non-coding regions are the binding sites for proteins, such as the SRY protein (see Chapter 2, p. 48), that regulate DNA folding, and thus regulate when a gene is transcribed.The human genome draft sequenceIn February 2001 two groups simultaneously announced completion of a draft of the sequence of the human genome. One group, the International Human Genome Sequencing Consortium, involving laboratories from the United States, Britain, Japan, France, Germany, and China, published their results in Nature (409: 860). The other group, a biotechnology company called Celera Genomics, published their results on the same day in Science (291: 1304). The draft covers about 94% of the estimated 3 billion bases in the complete genome. Of those 3 billion bases, 1 billion have been sequenced to completion, including all of those on the smallest paired chromosomes, chromosomes 21 and 22. The other 2 billion bases contain gaps and areas where different efforts at sequencing have resulted in different answers.Completion of the draft sequence supported some previously established hypotheses, but also produced some surprises. Some key results are:About 95% of the human genome represents non-coding DNA, a large proportion of which is composed of repetitive sequences. Less than 5% of the human genome is composed of genes, sequences that code for RNAs or proteins. It has been known for a while that the complexity of an organism does not correlate with the size of its genome. Much of the excess size is due to these non-coding, repeat sequences. Detailed knowledge of these sequences is opening up a new resource for studying evolution. These sequences can be likened to living fossils carried within each of us. They are already used in population genetic studies examining the migrations of human populations.The actual number of genes is smaller than previously estimated. In humans it is difficult to predict which sequences represent genes, for reasons we discuss later. Thus, although the draft sequence of the human genome has been published, the number of genes remains unknown. The estimate of the number of genes is currently between 30,500 and 35,500. (Previous estimates had been between 50,000 and 100,000 genes.) The numbers of genes in the fruitfly (Drosophila melanogaster) and the roundworm (Caenorhabditis elegans) have been ascertained; comparisons reveal that humans are likely to have only twice as many genes as each of them.The protein products of many human genes remain unknown. It has been found that many of the known genes can be translated in different ways to produce alternative protein variants from the same gene (see Figure 4.10, p. 117). Thus, although we have only twice as many genes as fruitflies, we may have five times as many different proteins.A very high percentage of our genes are not unique to humans but are closely similar to comparable genes from other species. In fact, only 1% of human genes have no sequence similarity to any other organism. Our genes are similar to 46% of the genes in yeast, among the simplest organisms whose cells have a nucleus. Changes within genes over time provide clues to rates and paths of evolution.More than 200 human genes and their protein products have been found to have significant similarity to those in bacteria. These genes are not found in intermediate organisms such as fruitflies, and one school of thought suggests that these genes jumped from bacteria to humans or vice versa.Mutation rates differ in different parts of the genome. They are also higher in males than in females, although the reason for such a difference is not known.Within each gene, there is an average of 15 sites at which different individuals carry a different nucleotide, or at which the same individual may have a different nucleotide on each chromosome in a pair. These variations, called single-nucleotide polymorphisms, are greatly expanding how many alleles we think are possible for different genes. In addition, these small changes may affect the physiology of the organism possessing them. Some of these polymorphisms are associated with disease; most are not, but are instead associated with small changes in protein function or regulation. Knowledge of such small-scale variations continues to challenge our concepts of terms such as ‘heterozygous’, ‘dominant’ and ‘recessive’, and ‘allele’. It also makes it clear that there is no such thing as the human genome sequence. The genome sequence within each individual is unique.In April of 2003, only two years after publication of the draft sequence, the sequence of the human genome was completed. Its publication in the journal Nature was timed to coincide with the fiftieth anniversary of Watson and Crick’s article describing the double helical structure of DNA.Mapping the human genomeAnother goal of the Human Genome Project was to map the human genome. Mapping a species’ genome means identifying the chromosomal location of each gene and the order of the genes relative to one another. Just determining the sequence of a piece of DNA does not tell you its location in the genome. The molecular techniques developed as part of the Human Genome Project have accelerated the mapping and identification of genes more generally.One way to map a large piece of DNA is to cut the same long piece with two different restriction enzymes, derive the sequence of each of the pieces, then use computers to discover how the two sets of pieces overlap. Figure 4.8 shows how sequence data from overlapping fragments of DNA are used to derive the original order of the fragments. Figure 4.8A shows two sets of fragments of DNA produced by cutting a DNA sample with different restriction enzymes. The first restriction enzyme cut theFigure 4.8(A)Combining the sequences of small pieces into the sequence of the original whole chromosome. Here are the fragments of a sequence cut with two different enzymes. Can you piece them together to reconstruct the complete sequence? Don’t turn the page until you’ve tried it!DNA into six pieces only; the second resulted in eight pieces. The bases in the sequences of each of the eight pieces can be lined up to match the bases in the six pieces. Can you see how you would use this idea to determine the order that the six pieces had originally been in? Now turn the page and look at Figure 4.8B.In our example the largest piece contains 40 bases. Actual DNA pieces for sequencing are around 500 bases in length. Because the pieces are so much longer and there are so many of them, computers are needed to line up the overlaps. The accuracy of the method increases with the length of the overlapping region. The longer the sequence of the overlap between two pieces, the higher the probability that the sequence will appear only once in the genome, allowing the unambiguous assignment of the position of the two pieces relative to each other.Celera used this approach first in 1995 with the complete sequencing of the genome of the bacteria Haemophilus influenzae. The same approach was used successfully on the genomes of the 599 viruses, 31 eubacteria, and 7 archaebacteria that were sequenced between 1995 and 2002. They believe that the same approach will work for mapping the human genome.But there are obstacles to applying this approach to mapping the human genome. One obstacle is size; the human genome is about 25 times larger than any previously sequenced genome, although it is far from being the largest genome known. (One species of single-celled amoeba has a genome 200 times larger than humans!) Another obstacle to accurate reassembly is the fact that much of the non-coding DNA in the human genome is composed of repeated sequences of nucleotides. This enormously complicates the job of putting pieces into unambiguous order. Species whose genomes had previously been sequenced do not contain these repeats, so it was much easier to determine which piecewent where in these genomes.In this example, a DNA sequence of 150 bases is cut with two different restriction enzymes, producing the following fragments, each of which has been sequenced.Fragments from the first restriction enzyme: GGTCGGCTATGTAACGAGTTGCC TCTTGTTCCTAGCTTGTCAACCGGGGATGAATGTTTACTGCACGCGGACCGTCGGTTCATGTCGCAGAGCCTATTGCGAGAAGT GCCCACCTTTTATTGAGTTGATGCTCGACGTAGCCAGACTTAAFragments from the second restriction enzyme: ACCGGGGATGAATGTTTACTGGTCGCAGAG CCTATTGCGAGAAGTGGTCGGCTACTTGTCATGATGCTCGACGT CGTCGGTTCAT AGCCAGACTTAACACGCGGACTGTAACGAGTTGCCGCCCACCTTTTATTGAGT TCTTGTTCCTAGTry to piece these fragmentary sequences together and determine the entire sequence of 150 bases, before you turn the page.The International Human Genome Sequencing Consortium therefore used DNA markers in addition to sequence overlap to map the locations of the pieces. In the technique used by the Consortium, the total DNA in the genome was split into 29,298 overlapping large fragments with a variety of restriction enzymes. Each large piece was further split into pieces of a size that could be sequenced. Sequencing of the small pieces has been proceeding at the same time as the mapping of the large fragments, and one advantage of this approach is that different laboratories can be simultaneously working on different pieces of the puzzle. Indeed, the location of each of the large fragments within the genome has now been mapped and the map is publicly available. Mapping of all of the small pieces is still proceeding.Because Celera started with all small pieces, the Consortium maintains that Celera will not be able to reassemble the sequences of their small pieces without referring to the publicly available data posted by the Consortium. Celera maintains that because the Consortium map and sequence data are publicly available, Celera should use it to help assemble their small pieces more quickly. Why continue to insist on the slow way, when those data can now be used in a more rapid way?The Consortium requires rapid, public disclosure of all data. Their decision to publish a draft sequence as fast as possible was driven, in their words, by “concerns about commercial plans to generate proprietary databases of human sequences that might be subject to undesirable restrictions on use” (Nature 409: 863). These worries have to do with the stated intentions of Celera Genomics to require others to pay for access to their databases.Some ethical and legal issuesMany of the issues already covered in Chapter 3 regarding genetic testing will become more commonplace as molecular genetics continues to change medicine. How does an individual’s right to privacy balance against family members’ desire to know the results of genetic tests or an insurance carrier’s or employer’s desire to cover or to hire only employees who will remain healthy? How does an individual’s desire to control their own reproduction balance against possible eugenic aims of society or against further stigmatization of disabled people? How can genetic counseling be value-free while providing education about genetics and not just about the testing procedure itself?When the Human Genome Project was funded, scientists saw theneed for examination of the ethical, legal, and social issues (anticipated and unanticipated) that would be raised by the research. One percent of the funding was set aside for this effort. The issues just mentioned are among those being studied, but there are many others. Social workers, anthropologists, ecologists, ethicists, and others are working together to examine the issues raised by the study of genetic variation in human populations and by the integration of genetic information into health care as well as into non-clinical settings. Others are studying the ways in which socioeconomic factors, race, and ethnicity influence people’s understanding, interpretation, and use of genetic information. Simultaneously, new genetic information continues to change our concepts of race and ethnicity (see Chapter 7). Others are examining how genetic knowledge and concepts interact with different philosophical and theological traditions. Many of the working groups have composed reports with their answers to many of these questions and their guidelines for the use of genetic information. These reports are available at the Web site www.genoma.govIn addition, data obtained from the Human Genome Project raise questions about ownership and patent rights. Who owns the human genome Figure 4.8(B) Here is the complete 150 base sequence. Geneticists often work with hundreds of fragments at a time, each larger than this complete sequence, making the task of putting them together much more difficult. Or the sequence of a specific gene? If a researcher locates a gene on a specific chromosome, can he patent the information? Can a genetic sequence be copyrighted like a book? Can the genes themselves be patented? Certain biotech companies can benefit greatly from commercializing gene sequences, testing gene sequences, or curing various genetic diseases, but sharing information about gene sequences seems, at first sight, to jeopardize their competitive position. . Several companies aim to identify as many gene sequences as possible, then record them and sell the information at a profit. Other scientists believe that the human genome should be public information and that scientists should share this information cooperatively, especially when public funding in the form of research grants was used to generate knowledge. A compromise is being developed, in which most sequences are published in publicly available databases, but sometimes there is a charge for this access. Wenn die beiden Sätze von Fragmenten auf diese Weise aneinandergereiht werden, ist die Reihenfolge der Basen in der ersten Reihe the same as the order of the bases in the second row.and the complete sequence is therefore as follows:TCTTGTTCCTAGCTTGTCAACCGGGGATGAATGTTTACTGGTCGCAGAGC- TCTTGTTCCTAGCTTGTCAACCGGGGATGAATGTTTACTGGTCGCAGAGC- TCTTGTTCCTAGCTTGTCAACCGGGGATGAATGTTTACTGGTCGCAGAGC-CTATTGCGAGAAGTGGTCGGCTATGTAACGAGTTGCCGCCCACCTTTTAT - CTATTGCGAGAAGTGGTCGGCTATGTAACGAGTTGCCGCCCACCTTTTAT- CTATTGCGAGAAGTGGTCGGCTATGTAACGAGTTGCCGCCCACCTTTTAT-TGAGTTGATGCTCGACGTAGCCAGACTTAACACGCGGACCGTCGGTTCAT TGAGTTGATGCTCGACGTAGCCAGACTTAACACGCGGACCGTCGGTTCAT TGAGTTGATGCTCGACGTAGCCAGACTTAACACGCGGACCGTCGGTTCATdeduced sequence fragments from first enzymefragments from second enzymeTHOUGHT QUESTIONSTo what extent do you stimme Watsons Aussage zu, dass die Sequenzierung des menschlichen Genoms uns sagen wird, was bedeutet es, ein Mensch zu sein? Suppose he knows the exact genetic sequence of part or all of the genome; What would you really know about yourself? If only stretches of DNA that are 500 to 700 bases long can be sequenced at a time, how many of these small stretches of DNA must be sequenced to determine the sequence of the entire human genome? (Also consider the overlaps required to assemble the sequences; assume an average of 10% overlap.) Will the DNA sequence of the human genome tell us which features are controlled by each part of the sequence? Will it tell us which sequences are genes and which are spacers? If you have a certain rare genetic condition and scientists use cell samples from your body to determine the DNA sequence of the gene, what rights (if any) does that give you to the information? Do scientists have the right to publish your genetic sequence or parts of it? Is it an invasion of your privacy? Can scientists sell information? If so, are you entitled to a share of the winnings? Genomics is a new field of biology that developed as a result of the Human Genome Project, which also funded the sequencing of the genomes of many other species. This may seem strange at first, since the name of the project specifies the human genome, but there were several reasons for including these other species. The study of the genomes of species has become an entirely new area of biology called genomics. This field has emerged to help unravel the mysteries of human genes now that sequencing and mapping nears completion. One approach to genomics is the identification of individual human genes. The combination of molecular biology and informatics required to navigate the vast amounts of data produced by the various genome projects is known as bioinformatics. -achieve applications found outside of genetics. DNA sequencing and mapping would not have been practical before the advent of large computers. Although the techniques for sequencing short fragments of DNA are fairly simple (see Figure 4.7), finding the overlaps that indicate how the sequenced short fragments were originally ordered (see Figure 4.8) requires enormous computational power. Then, when the longest sequences were determined, storing the data required the development of ever-larger computer databases and new methods to search for them. Genomics requires the development of new computer programs. The need for people trained in molecular biology and computer science who can work with this data has made bioinformatics a rapidly growing new field of employment. A research project within bioinformatics has been the development of computer programs to locate genes in a genome. In the past, as we've seen, scientists have worked backwards from a trait to find a gene. Now that the genome sequence is complete for many species and nearly complete for humans, the method of gene discovery has changed. Now the people themselves are examining the sequence data, trying to determine which parts might be genes without first knowing a trait or function of those genes. Many of these genes have already been found in bacteria and yeast and are called "orphan genes" because they had no known function at the time of their discovery. (Further identification of its function is part of the functional genomics research program described below.) In bioinformatics, people program computers to scan sequence data to locate genes, that is, regions that code for RNA and proteins. To do this, programmers must recognize the "rules" of the genetic code: what features of a sequence distinguish a coding region from a non-coding region? The computer search for genes within sequences is called gene scanning. (A) Bacterial genes contain only coding regions; that is, all DNA is transcribed into mRNA. (B) In eukaryotic cells, non-coding regions that are not transcribed lie within the coding regions of genes. © In humans (a eukaryotic species), the amount of non-coding DNA is much greater than the amount of DNA that codes for a protein product. (A) Genetic scanning of the coding region in different organisms. Interestingly, most genes begin with the ATG codon and end with one of three "stop codons": TAA, TAG, or TGA. If nucleotides A, T, G, and C were randomly assigned, one would expect each of the stop codon triplets to occur every 43 or 64 bases on average. But nucleotides are not randomly distributed within genes; they are maintained in a nonrandom pattern as a result of evolution because they encode a product that confers an advantage on the organism. In bacteria, genes are typically 300 to 500 codons long, contiguous, and do not overlap. Also, bacteria have very little non-coding DNA. These factors make scanning bacteria for genes relatively easy. A computer can scan the sequences that follow each ATG and find the regions where the next stop codon is located a few hundred bases away. Gene scanning is much more difficult in other organisms, namely nucleated organisms (eukaryotic organisms; see Chapter 5). Unlike bacterial species, they have long non-coding stretches of nucleotides (called introns) spread out over much shorter regions that correspond to codons. While the coding regions (called exons) are approximately the same length in different species, the size of the non-coding introns is much larger in humans than in other species (Figure 4.9). In the human genome, less than 5% is within the genes; moreover, within these human genes, only about 5% of the nucleotides comprise coding sequences. This makes it difficult to use raw sequence data to predict which nucleotide regions represent genes. Therefore, gene scanning programs continue to be refined to incorporate up-to-date knowledge of the characteristics of "deviations from randomness" within genes in species other than bacteria. Such a deviation from randomness is called "codon bias": a given species does not use all codons equally. For example, the amino acid alanine may be encoded by four different codons in humans; Moreover, three of them are used much more often than the fourth. In a non-coding region of the genome, all codons are equally likely to be represented, but in a coding region, one codon is less abundant. The presence of non-coding regions within genes is clearly a complication of genetic scanning. What benefit could an organism have if its genes were interrupted by such non-coding regions? It is these decoding sections that made the shorter encoding segments possible.
(B)
gene (1000 nucleotides)DNArecombine to form new genes. This provides a mechanism for rapid genetic change (more rapid than by mutation). New genes are pro-duced by the novel assembly of parts. There is another way in©coding regions (exons)genenoncoding regions (introns)DNAwhich the division of genes into many coding regions is adaptive, and that is in providing a mechanism by which slightly different versions of a protein can be made in different tis-sues, adapted to the cellular coding regions noncoding regionshuman Factor VIII gene (200,000 nucleotides)DNAenvironment and function of that tissue. An example is shown in Figure 4.10. Thehuman gene for a protein called -tropomyosin contains many coding regions scattered among non-coding regions. This gene can be tran-scribed to mRNA in different ways, so that in the cells of one tissue one set of coding regions is used, and in the cells of another tissue, a different set of coding regions is transcribed. This results in different mRNAs in the different cells, and therefore in slightly different proteins after translation.Each protein is still -tropomyosin, but with a slightly different aminoacid sequence and therefore a slightly different functional capability.Although scientists think these large non-coding regions within genes are adaptive for the organism, they do present a significant obstacle to identifying genes by gene scanning. In fact, it does not appear that gene-scanning programs alone will be able to identify all of theFigure 4.10Within human genes all of the nucleotides are transcribed into RNA but only some of the RNA nucleotides are translated into protein. genes in a eucaryotic genome. Hence, the Human Genome Project also funded work on the genomes of other species, so that human genes could be located by comparison with the genes of other species, a field now known as comparative genomics.coding regionsnon-coding regions-tropomyosin genetranscription and splicingDNA strandmRNA for tropomyosin in striated muscle mRNA for tropomyosin in smooth muscle mRNA for tropomyosin in fibroblast cells mRNA for tropomyosin in brain cellsComparative genomicsWhen scientists compare sequences of genes from one species with those from another, they are working in the field of comparative genomics. The size of the genome of many species has been determined. As we saw earlier, the overall size does not always correlate with the complexity of the organism. This is due to the very great differences in the amount of noncoding DNA in various genomes, so that overall size does not correlate with the numbers of genes present.As we have just discussed, genes are much easier to identify in some species than in others. Once a gene has been identified and its sequence determined in one species, there is often enough sequence similarity for its counterpart gene (or genes) to be located in other species. This is the major reason why other species’ genomes were also examined as part of the Human Genome Project. Another reason was that sequencing the genomes of other species allowed scientists to develop the technology that was later used to analyze human genome sequences.Many human genes have been located by their similarity to yeast genes. A yeast cell, like a human cell, has a nucleus and many of its genes have remained very similar to the counterpart genes in humans. Animals are even more similar and one animal that is proving to be quite useful in comparative genomics is the pufferfish, Fugu rubripes. Its genome is only one-seventh the size of the human genome, yet it is estimated to have the same number of genes. Because of its small genome size, gene location is much easier in pufferfish, and may subsequently allow mapping of the human counterpart genes. The mouse genome is almost complete, andmany more human genes will be found by comparison with those in the mouse. Many known genes in mice are located in the same order on their chromosomes as they are on human chromosomes, and this correspondence is extremely helpful in mapping genes. The mouse genome, however, is even larger than the human genome, so the problems of working with a large genome still pertain. See our Web site for information on the sizes of the genomes of various species (under Resources: Genome sizes). Aside from its usefulness in locating human genes, comparative genomics has produced new data for evolutionary biologists. Species that have a common ancestor have more genes and more nucleotide sequences in common than species that do not. Unfortunately, the scientists working on a particular species have often independently devised the database for each species’ genome. Consequently, another goal of bioinformatics is to devise ways of making the different databases com-patible and interactive, thereby facilitating comparative genomics.In addition to finding similarities between species, comparative genomics has led to the realization that within a species there are groups of genes that share large portions of their sequences. These ‘gene families’ are presumed to have evolved from a common ancestral gene. Finding one gene in the family enables the others to be located, and most often the different protein products of the family members to be identified. For example, the human hormones oxytocin and vasopressin (both proteins) belong to the same gene family, and they have very similar amino acid sequences and genes that code for them. The same is true of the oxygen-carrying proteins hemoglobin and myoglobin.Functional genomicsIn Chapter 3 we described how Archibald Garrod and other scientists studied “inborn errors of metabolism,” disease conditions caused by changes in biochemical pathways. The study of similar changes in bacteria or yeast have often led to the discovery of entire chains of biochemical reactions. In the past, scientists looking for the molecules involved in such a biochemical pathway, would start with a trait and work backwards to a protein. Pedigrees such as we saw in Chapter 3 would be linked with different forms of a protein. After purifying the protein and discovering its amino acid sequence, its gene sequence could be inferred. Gene sequencing turns this whole process around. Genes are found by linkage to DNA markers, and only later is the protein product found. However, finding a gene, mapping its location, sequencing it, and even deriving the amino acid sequence of its protein product, will not tell us its function.New sequences can be compared with those whose function is already known. This is the field of functional genomics. Species that can be easily manipulated experimentally have been most useful in discovering gene functions. The zebrafish is a vertebrate that reproduces rapidly, and many of its internal structures are visible in the living fish because overlying structures are transparent. For these reasons, zebrafish have become an experimental species of great interest to scientists working on the genetics of development. An even simpler species, the yeast Saccharomyces cerevisiae, has been found to share many genes with humans. Gene functions that were discovered in yeast have proved to have paral-lels with disease-associated gene mutations in humans. For some examples see our Web site, under Resources: Yeast genes. The functions of the yeast genes are discovered by several methods. One is to examine which genes are transcribed to mRNA when the yeast undergoes a particular response or function; another is to inactivate (mutate) a gene and see what effect this has. Once the sequence of a gene is known, it is relatively easy to mutate it by manipulating the DNA causing a change in the protein product, which is now not functional. The opposite approach can also be used: extra copies of the gene can be inserted and observations made of the change in function under different environmental conditions. These approaches are not confined to yeast, but are also done to discover gene functions in mice and other species.Earlier in this chapter we saw how a gene could be added to a genome, using a vector. In Figure 4.4 we saw how the functional gene for ADA was added to the genome in human cells. This method adds a gene, but in an unpredictable location within the genome. The non-functional gene is still present, and indeed one of the possible dangers of the technique is that the new gene may get added in a place that disrupts some other gene. More recently, methods have been developed for changing the sequence of a specific gene. In theory, this technique could be used to repair a non-functional gene, to mutate a gene in a specific way, or to disrupt a functional gene. A vector is used to carry into the cell a piece of DNA partly complementary to the gene to be altered. The introduced double-stranded DNA becomes substituted for the gene region as a result of crossing-over at two sites where the insert and the gene have the same sequences (Figure 4.11). If the inserted DNA is non-functional, as shown in this example, the normal gene is disrupted. The effect of deletion of that gene’s protein can then be studied in the offspring cells (yeast or tissue culture of human cells). If the gene disruption is carried out on a cell from a very early stage of development, an entire organism can develop that is lacking the gene and its protein product. (This topic, part of stem cell research, is covered in more detail in Chapter 12.) Mutated mice with particular genes nonfunctional or ‘knocked out’, or mice with overexpressed genes produced by the insertion of additional copies of a functional gene, have led to important clues to the functions of human genes. Families of genes have been found within species that have structurally related protein products but very often quite different functions. This has led scientists to realize that gene duplication and mutation can occur first, and that new functions can follow. Of course, a gene that is present in just a single copy cannot change to a new form (possibly witha new function) without giving up its original form and function.Figure 4.11In human genes, different combinations of coding regions can be transcribed to produce different mRNAs in different tissues.A duplicated gene, however, can undergo changes in one copy (possibly evolving new functions) while the other copy remains unchanged.ProteomicsJust as the complete DNA sequence of an organism is its genome, the complete protein content of that organism is its proteome. Proteomics is the study of how the protein content changes over time in a cell and in an organism, how it differs in different tissues,chromosomal DNArecombination at two sitesdisrupted genevector DNATHOUGHT QUESTIONSand how it relates to the health and function of the organism. Proteins are synthesized as a result of transcription of genes and translation of mRNA, as we saw in Chapter 3. However, there are further modifications to a protein after it has been translated that affect both its activity and its concentration. No protein stays in a cell forever; all are degraded and removed. We will see more about these aspects of protein function in cells in Chapter 12.Knowing the DNA sequence of genes has hastened the discovery of the amino acid sequence of proteins. Computer programs use the known energies and bond angles of chemical bonds to turn amino acid sequence data into molecular models of the three-dimensional shape of a protein or portion of a protein. Having the ability to visualize these shapes by computer graphics has led to new strategies for the design of medicines. In the past, natural products and synthetic compounds were randomly tested in functional assays to see which would work for a particular need. Now small molecules can be designed to exactly fit a critical enzymatic site of a protein. Once the molecule has been designed by computer simulation, medicinal chemists then synthesize it and biologists test to see whether it has the desired outcome of blocking the protein’s function. The action of such drugs is far more specific, and the drug will therefore have fewer side-effects than traditionally developed drugs, for reasons we will study in Chapter 14.To synthesize a protein with even a slightly different structure can be very difficult and costly. However, once the sequence for the gene coding for that protein is known, it becomes relatively easy to modify the protein by changing the sequence of its gene. Roughly the same technique as that in Figure 4.11 is used, but the inserted piece of DNA differs from the normal piece by only a few nucleotides. Such modifications can, for example, lead to the development of proteins that are stable under a wider variety of conditions. These proteins find a variety of industrial applications. Stain removers in laundry detergents, altered enzymes for food processing, and cleanup of pollution, are just a few examples.Rather than studying one protein change at a time, proteomics also has another goal: to study all of a cell’s proteins in the aggregate. Such a goal has been unattainable in the past, and is a big factor explaining why reductionism (reducing a problem to its simplest form) has been a widespread experimental approach in biology. Proteomics is in its infancy, but promises to be a much more integrative approach.1 In what ways are humans poor subjects for genetic research? In what ways are humans good subjects? Which of your reasons are purely biological, and which have ethical components?Why are certain traits studied in some species and not others?Will genomics allow the findings in one species to be applied in other species? Why or why not?Summary to Chapter 4 121Concluding RemarksAs genomics has discovered genes with useful properties within one species, genetic engineering has given us the tools to transfer those genes into another species. The Human Genome Project has discovered that transfer of genes from one species to another does also occur in nature. Viral and bacterial genes are found in the human genome, for example. Because we have almost always studied the effect of one gene or one protein at a time, transferring a gene into a new genomic environment may lead to different results from those that we expect. As we develop the tools to alter genomes, proteomics may give us the ways to study the effects of such changes throughout the cell. We also need to be mindful of effects at the level of the whole organism and effects of genetic engineering on ecosystems as well, which we will explore further in Chapter 11.Chapter SummaryRestriction enzymes cut DNA into fragments with known sequences at their ends. Restriction enzymes that produce fragments with singlestranded sticky ends are used in genetic engineering to splice new genes into genomes.Variations in the lengths of these fragments are called restriction-fragment length polymorphisms or RFLPs. RFLPs have helped in finding the location of many genes, as well as in the identification of individuals and in genetic engineering.Genetic engineering consists of inserting functional genes into cells, thereby altering the cell’s genotype. The recipient cells may be bacterial cells that may then acquire the ability to make certain human proteins, or they may be human cells that acquire a functional allele and are injected into a patient as gene therapy.Bacterial plasmids are used to carry genes into a new species.A genome is the total genetic information carried by a particular organism. The Human Genome Project has now produced a draft sequence and map of the human genome.DNA markers of various kinds have allowed the mapping of genes to locations within the genome. Markers also allow the identification of individuals.Genomics is the study of the genome, either the comparison of genomes of different species or as a method of discovering gene functions.Bioinformatics combines computer science and molecular biology in the analysis of genomes and the identification of genes within a genome.Proteomics is the study of all of the proteins present within a cell.PRACTICE QUESTIONSIf one individual human differs from another in 0.1% of the genome, how many bases are different?In the following stretch of DNA, how many fragments will result from digestion with the HaeIII restriction enzyme shown in Figure 4.1? How many will result from digestion with EcoRI?strand 1A T C C G T A G G C C T A A C C A T C C T A G T G C T A G G C A T C C G G A T T G G T A G G A T C A C Gstrand 2Why are restriction enzymes that produce fragments with ‘sticky ends’ more useful in genetic engineering than restriction enzymes that produce fragments with ‘blunt ends?’Could the following sequence be used as an insert into genomic DNA? Why or why not?strand 1A A G C T T A A C G G A T T A G C A A G CC G A A T T G C C T A A T C G T T C G A Astrand 2Could the following sequence be used as an insert into genomic DNA? Why or why not?strand 1A A G C U U A A C G G A U U A G C A A G CC G A A U U G C C U A A U C G U U C G A Astrand 2When a plasmid is being cut with a restriction enzyme in preparation for inserting a DNA fragment, the plasmid needs to be cut with the same restriction enzyme as was used to make the DNA fragment. Why?Can DNA marker band patterns be used to identify maternity, as well as paternity?Can DNA marker testing be used to identify individual organisms in other species besides humans?IssuesDid life evolve?Is science compatible with religion?How does evolution relate to genetics?How do new species originate?Is life still evolving?Will life continue to evolve?Is the science of evolution static or changing?Evolution (descent with modification, natural selection)Fossils and geologic timeEnvironmental influences on species
adjustment
Form and functionSpecies and speciationOrigin of lifeChapter OutlineThe Darwinian Paradigm Reorganized Biological ThoughtPre-Darwinian thoughtThe development of Darwin’s ideas Descent with modificationNatural selectionA Great Deal of Evidence Supports Darwin’s IdeasMimicryIndustrial melanismEvidence for branching descent Further evidence from the fossil record Post-Darwinian thoughtCreationists Challenge Evolutionary ThoughtBible-based creationism Intelligent designReconciling science and religionSpecies Are Central to the Modern Evolutionary ParadigmPopulations and species How new species originateLife on Earth Originated by Natural Processes and Continues to EvolveEvolution as an ongoing process5123124Evolutionsk any biologist to name the most important unifying concepts in biology, and the theory of evolution is likely to be high on the list. Asgeneticist Theodosius Dobzhansky explained, “nothing in biology makes sense, except in the light of evolution.” However, many people in the United States are unaware of the importance of evolution as a unifying concept: public opinion surveys reveal that 25–40% of Americans either do not believe in evolution or think that evidence for it is lacking. (The percentage varies depending on how the question is worded.) In this chapter we examine both the theory of evolution and the opposition to it.As explained in Chapter 1, scientists use the word ‘theory’ for a coherent cluster of hypotheses that has withstood many years of testing. In this sense, evolution is a thoroughly tested theory that has withstood nearly a century and a half of rigorous testing. Scientific evidence for evolution is as abundant as, and considerably more varied than, the evidence for nearly any other scientific idea. To refer to evolution as “just a theory” is thus a grave misunderstanding of both scientific theories in general and evolutionary theory in particular. When physicists speak of the atomic theory or the theory of relativity, or when medical professionals speak of the germ theory of disease, they are speaking of great unifying principles. These principles are now well established, but they have withstood repeated testing for somewhat fewer years than the theory of evolution has. Educated people no longer doubt the existence of atoms or of germs, and nobody refers to any of these concepts as ‘just a theory.’ In the way that the atomic theory is a unifying principle for much of physics and chemistry, the theory of evolution is a unifying principle for all of the biological sciences.The Darwinian Paradigm Reorganized Biological ThoughtArguably the most influential biology book of all time was published in 1859. On the Origin of Species by Means of Natural Selection, written by the English naturalist Charles Darwin (1809–1882), contains at least two major hypotheses and numerous smaller ones, along with an array of evidence that Darwin had already used to test these hypotheses. Both hypotheses deal with evolution, the process of lasting change among biological populations. Together, these hypotheses offer explanations for the origins and relationships of organisms, the great diversity of life on Earth, the similarities and differences among species, and the adaptations of organisms to their surroundings.The first major hypothesis, branching descent, is that species alive today came from species that lived in earlier times and that the lines of descent form a branched pattern resembling a tree (Figure 5.1). Darwin used this hypothesis, which he called “descent with modification,” to explain similarities among groups of related species as resulting fromcommon inheritance. The second major hypothesis is that parents having genotypes that favor survival and reproduction leave more offspring, on average, than parents having less favorable genotypes for the same traits in a given environment. Darwin called this process natural selection, and he hypothesized that major changes within lines of descent had been brought about by this process. Both of these two hypotheses are falsifiable, and they have been tested hundreds if not thousands of times, without being falsified, since Darwin first proposed them in 1859. Darwin’s two hypotheses made sense of several previously noticed but unexplained regularities in anatomy, classification, and geographic distribution. As both a unifying theory and a stimulus to further research, Darwin’s Origin of Species fits the concept of a scientific paradigm expounded by Thomas Kuhn and explained in Chapter 1 (p. 13). Modern evolutionary thought is still largely based on Darwin’s paradigm of branching descent and natural selection, expanded to include the findings of genetics.Pre-Darwinian thoughtDarwin’s evolutionary theory was not the first. An earlier theory had been proposed by the French zoologist Jean-Baptiste Lamarck in 1809. Lamarck believed in what he called la marche de la nature (the parade of nature), a single straight line of evolutionary progress. This idea was based in part on the earlier idea of a scale of nature, called ‘scala naturae’ in Latin or ‘chain of being’ in English, an idea described on our Web site (under Resources: Scala naturae).Lamarck also noticed that species were adapted to local environments. An adaptation is any feature that enables a species to survive in circumstances in which it could not survive as well without the adaptation. Adaptations had been observed since ancient times, but scientists of Lamarck’s generation were among the first to propose hypotheses to explain adaptation. Along with several contemporaries, Lamarck was an environmental determinist, meaning that he believed in the almost limitless ability of adaptation to mold speciesto their environments and achieve a per-Figure 5.1The pattern of branching descent. Living species in the top row are descended from the ancestors below them.The red circle represents the common ancestor to all other circles, and the red square is likewise ancestral to all the squares. The red hexagonal shape at the bottom is ancestral to all species shown in this family tree. In a classification, all the squares would be placed in one group and all the circles in another.living species fect match. Each environmental determinist favored a different explanation for adaptation. Lamarck’s own explanation was based on the strengthening or increase in size of body parts through repeated use, or their weakening or decrease in size through disuse. Lamarck thought that such changes, acquired during the life of an individual, would be passed on to the next generation, but we now know that these acquired characteristics are not inherited and do not contribute to evolution. Other scientists, including Darwin, recognized adaptation to the local environment as an important phenomenon. However, Darwin differed from the determinists in seeing important limitations to the ability of adaptation to modify species.more recentextinct species ancestral to all species shown as squaresmore ancientextinct species ancestral to all species shown as circlescommon ancestor of all species in the treeBritish naturalists had quite different explanations for adaptation. The Natural Theology movement, led by the Reverend William Paley, sought to prove the existence of God by examining the natural world for evidence of perfection. By careful examination and description, British scientists found case after case of organisms with anatomical structures so well constructed, so harmoniously combined with one another, and so well suited in every detail to the functions that they served that one could only marvel at the degree of perfection achieved. Such harmony, design, and detail, they argued, could only have come from God. Paley offered well-planned adaptation as proof of God’s existence: “The marks of design are too strong to be gotten over. Design must have a designer. That designer must have been a person. That person is God.” (Paley, Natural Theology, end of Chapter 23; page numbers vary among many editions.) In a nation in which many clergymen were also amateur scientists, it became fashionable to dissect organisms down to the smallest detail, all the better to marvel at the wondrously detailed perfection of God’s design. A large series of intricate and sometimes amazing adaptations were thus described, which Darwin would later use as examples to argue for an evolutionary explanation based on natural selection.The publication of On the Origin of Species challenged many scientific ideas, including those of Lamarck and Paley, and it thus caused controversy among scientists. Some people felt that it also challenged social and religious views that had been taught for centuries. Today, there are still people who are antievolutionists and we discuss their ideas later in this chapter.The development of Darwin’s ideasFrom 1831 to 1836, Charles Darwin traveled around the world aboard the ship H.M.S. Beagle. His observations in South America convinced him that the animals and plants of that continent are vastly different from those inhabiting comparable environments in Africa or Australia. For example, all South American rodents are relatives of the guinea-pig and chinchilla, a group found on no other continent. South America also had llamas, anteaters, monkeys, parrots, and numerous other groups of animals, each with many species inhabiting different environments throughout the continent, but different from comparable species elsewhere (Figure 5.2). This was definitely not what Darwin had expected! Environmental determinist theories such as Lamarck’s had led Darwin to expect that regions in South America and Africa that were similar in climate would have many of the same species. Instead, he found that most of the species inhabiting South America had close relatives living elsewhere on the continent under strikingly different climatic conditions. They had no relationship, however, to species living in parts of Africa or Australia with similar climates. The animals inhabiting islands near South America were related to species living on the South American continent. Fossilized remains showed that extinct South American animals were related to living South American species. “We see in these facts some deep organic bond, prevailing throughout space and time, over the same areas of land and water, and independent of their physical conditions. The naturalist must feel little curiosity, who is not led to inquire what this bond is. This bond, on my theory, is simply inheritance, that cause which alone, as far as we positively know, produces organisms quite like, or…nearly like each other.” (Darwin. Origin of Species, 1859, p. 350.)The Galapagos Islands. The Galapagos Islands are a series of small volcanic islands in the Pacific Ocean west of Ecuador. Darwin’s visit to these islands proved especially enlightening to him. In this archipelago, a very limited assortment of animals greeted him: no native mammals or amphibians were present; instead there were several species of large tortoises and a species of crab-eating lizard. Most striking were the land birds, now often called ‘Darwin’s finches’ (phylum Chordata, class Aves, order Passeres): a cluster of more than a dozen closely related species, each living on only one or a few islands (Figure 5.3). The tortoises also differed from island to island, despite the clear similarities of climate throughout the archipelago. Darwin hypothesized that each species cluster had arisen through a series of modifications from a single species that had originally colonized the islands. The islands, Darwin noted, were similar to the equally volcanic and equally tropical Cape Verde Islands in the Atlantic Ocean west of Senegal, which Darwin had also visited, but the inhabitants were altogether different. Darwin concluded that the Galapagos had received its animal colonists (including the finches) from South America, while the Cape Verde Islands had received theirs from Africa, so in each example the closest relatives were found onFigure 5.2An assortment of South American mammals. These species are very different from the mammals found on other continents, even where climates are similar. chinchillatapirtree sloth agouticoatimundipaca spider monkeyarmadillokinkajou guanacogiant anteater the nearest continent, not on geologically similar or climatically similar but distant islands. Geographic proximity, in other words, was often more important than climate or other environmental variables in influencing which species occurred in a particular place.Descent with modificationAs the result of his studies of species distribution on continents and on islands, Darwin concluded that each group of colonists had given rise to a cluster of related species through a process of branching descent. He called this process “descent with modification,” and he emphasized that each species in the cluster had been differently modified from a common starting point. Darwin was the first evolutionary theorist to emphasize that clusters of related species indicated a branching pattern of descent, a series of treelike branchings in which species correspond to the finest twigs, groups of species to the branches from which these twigs arise, larger groups to larger branches, and so forth (see Figure 5.1). In this diagram, each branch point represents a time of species formation and genetic divergence, and the base of the tree represents the common ancestor of all the species that arose from it. Darwin useda very similar treelike diagram, the only illustration in his book.Darwin found many large groups of related animal species inhabiting each continent. These groups were unrelated to the very different groups inhabiting similar climates on other land masses. Several large land areas had flightless birds, but they differed strikingly from one continent or island to the next: rheas in South America, kiwis and extinct moas in New Zealand, emus and cassowaries in Australia, extinct elephant birds on Madagascar, and ostriches in Africa. Each land mass had its own distinct type of flightless bird, although they all lived in regions of similar climate. Theories of environmental determinism (such as Lamarck’s) could not explain these differences, nor could theories of divine creation explain why God had seen fit to create half a dozen distinct types of flightless birds where one might have sufficed.Before Darwin’s time, biological classifications had already taken their modern hierarchical form, as described in Chapter 6, and as illustrated in Figure 6.1. Darwin explained this hierarchy as the natural result of branching descent with modification, a process that produces the similarities and differences that biologists have used in classifying organisms.Natural selectionWhen Darwin returned to England, he began reading about the ways in which species could be modified. How, he wanted to know, could a single colonizing species produce a whole cluster of related species on a group of islands? To help find clues to answer this question, Darwin contemplated the results of plant and animal breeding in Britain. During the preceding hundred years, British breeders had produced many new varieties of plants, such as roses and apples, and animals, including dogs, sheep, and pigeons, by careful breeding practices. Through these same practices, the breeders had greatly improved wool yields in sheep, and milk yields in cattle. By methodically selecting the individuals in each generation with the most desired traits and breeding these individuals with each other, the breeders had modified a number of domestic species through a process that Darwin called artificial selection. This process simply took advantage of the natural variation that was present in each species, yet it produced breeds that were strikingly different from their ancestors. Darwin remarked that some of the domestic varieties of pigeons or dogs differed from one another as much as did natural species, despite the fact that the domestic varieties had been produced within a short time from a known group of common ancestors. Could a similar process be at work in nature?At about the same time, Darwin read Thomas Robert Malthus’ Essay on Population (see Chapter 9, p. 287). Malthus emphasized that, in the natural world, each species produces more young than are necessary to maintain its numbers. This overproduction is followed in each generation by the premature death of many individuals and the survival of only a few. When Darwin compared this process with the actions of the animal breeders, he concluded that nature was slowly bringing about change in each species. Individuals varied in every species, and those that died young in each generation differed from those that survived to maturity and mated to produce the next generation. In this ‘struggle for existence,’ he hypothesized that…individuals having any advantage, however slight, over others, would have the best chance of surviving and of procreating their kind…. On the other hand, we may feel sure that any variation in the least degree injurious would be rigidly destroyed. This preservation of favourable variations and the rejection of injurious variations, I call Natural Selection…. Natural selection…is a process incessantly ready for action, and is as immeasurably superior to man’s feeble efforts, as the works of Nature are to those of Art. (Darwin. Origin of Species, 1859, pp. 61, 81.)All modern descriptions of natural selection are stated in terms of the concepts of genetics outlined in Chapter 2. New genotypes originate by mutation and by recombination, both of which act prior to any selection. Darwin, of course, knew nothing of mutations or of modern genetics, but he did realize that heritable variation had to come first and that “any variation which is not heritable is unimportant to us.”Natural selection may be defined as consistent differences in what Darwin called “success in leaving progeny,” meaning the proportion of offspring that different genotypes leave to future generations. The relative number of viable individuals that each genotype contributes to the next generation is called its fitness, and natural selection favors any trait that increases fitness. Darwin’s theory of natural selection is the basis for all modern explanations of adaptation.Many agents of natural selection operate in nature. Often, the selecting agents are predators. Selection by predators may be convenient to study, but many other agents of selection are known. Any cause of death contributes to natural selection if it reduces the opportunity for reproduction and if some genotypes are more likely to die. Some genotypes may be more susceptible to particular diseases or parasites, and die in greater numbers from these causes, while other genotypes might be more resistant and thus survive more readily. Starvation and weatherrelated extremes of cold, dryness, or precipitation may also be agents of selection if some genotypes can survive these conditions better than others. These and other causes of mortality are all agents of selection if there are differences in the death rates for different genotypes.Not every agent of selection causes death, however. Natural selection also favors those genotypes that reproduce more and leave more offspring. A special type of selection, called sexual selection, operates on the basis of success (or lack of success) in attracting a mate and reproducing. For example, animals of many species attract their mates with mating calls (such as bird songs), visual displays (as in peacocks; see Figure 8.2, p. 253), or special odors (as in silkworm moths or many other invertebrate animals). Individuals that do not perform well enough to attract a mate may live long lives but leave no offspring.THOUGHT QUESTIONS1 Darwin did not initially use the expression “survival of the fittest.” The phrase was first used by the British social philosopher Herbert Spencer, and was popularized especially by those who saw Darwinism as a license for unbridled, cutthroat competition in the era of the ‘robberbarons.’ (Darwin did adopt the expression in his later editions.) Do you think that this expression accurately reflects Darwinian thought regarding the animal and plant kingdoms?In what ways does it not?A Great Deal of Evidence Supports Darwin’s IdeasDarwin had proposed two major hypotheses: branching descent (“descent with modification”) acting over long periods of time, and natural selection as a mechanism that explained how evolutionary change takes place. In the years since Darwin proposed these two hypotheses, many scientists have used scientific methods to conduct thousands of tests of both hypotheses. The results of these tests have yielded much evidence that supports the hypotheses, and none that falsifies them.MimicryOne of the earliest tests of Darwin’s hypothesis of natural selection involved the phenomenon of mimicry, in which one species of organisms deceptively resembles another. In one type of mimicry, a distasteful or dangerous prey species, called the model, gives a very unpleasant and memorable experience to any predator that attempts to eat it. Predators always avoid the model after such an unpleasant experience. A palatable prey species, the mimic, secures an advantage if it resembles the model enough to fool predators into avoiding it as well.Selection by predators explains mimicry rather easily. Any slight resemblance that might cause a predator to avoid the mimic as well as itsmodel is favored by selection and passed on to future generations of the mimic species, while individuals not protected in this way would be eaten in greater numbers. Predator species differ greatly in their abilities to distinguish among prey species, so a resemblance that fools one predator might not fool another. Any advantage that increases the number of predators fooled is favored by selection, causing closer and closer resemblance to evolve with the passage of time.Sometimes several species that resemble each other are all distasteful to predators. Predators learn to avoid distasteful species, but a certain number of prey individuals are killed for each predator individual that learns its lesson. Without mimicry, each prey species must sustain this loss separately. Mimicry allows predators to learn the lesson with fewer individuals of each prey species dying in the process. The mimicry therefore benefits each prey species and is thus favored by natural selection.Mimicry often varies geographically. Some wide-ranging tropical species mimic different model species in different geographic areas. The deceptive resemblance is always to a species living in the same area, never to a far-away species. Environmentalist theories such as Lamarck’s had no way to account for the evolution of mimicry, and the patterns of geographic variation could not be explained by either environmentalist theories or by Paley’s natural theology. Natural selection, however, explains the variation as resulting from selection by predators.In a well-known case of mimicry, the model is the monarch butterfly, a distasteful species that feeds on milkweed plants. An unrelated species, the viceroy, is similar in superficial appearance, and is thus avoided by many predators (Figure 5.4); some of these predators may find the viceroy distasteful as well.Industrial melanismThe power of natural selection is also demonstrated by a phenomenon called industrial melanism, when darker colors evolve in areas polluted by industrial soot in species that are usually light in color elsewhere. In the British Isles, a species known as the peppered moth (Biston betularia) (phylum Arthropoda, class Insecta, order Lepidoptera) had long been recognized by an overall light gray coloration with a salt-and-pepper pattern of irregular spots. A black variety of this species was discovered in the 1890s. The black moths increased until they came to outnumber the original forms in some localities (Figure 5.5). The British naturalists E.B. Ford and H.B.D. Kettlewell studied these moths for several decades from about 1944 onward. Downwind from the major industrial areas, the woods had become polluted with black soot that killed the lichens grow-Figure 5.4An example of mimicry.Limenitis arthemis, a nonmimic relative of (B) Limenitis archippus, the viceroy. The viceroy resembles the unrelated monarch butterfly(C, Danaus plexippus), the model. The monarch is avoided by predators after just a single unpleasant experience (D, E). The warning color pattern of the monarch helps predators learn to avoid it; the viceroy is protected because its color pattern mimics that of the monarch.Butterfly closely related to the species from which the viceroy evolvedViceroy (C) Monarch (D) Blue jay eating monarch(E) Blue jay vomiting after eating monarchFigure 5.5Industrial melanism in peppered moths in the British Isles.ing on the tree trunks. Most of the moths living on the darkened tree trunks in these regions were black. However, where the woods were untouched by the industrial soot, the tree trunks were still covered with lichens and the moths had kept the light-colored pattern. Ford and Kettlewell hypothesized that the moths resembling their backgrounds would be camouflaged and thus harder for predators to see. To test this hypothesis, they pinned both light and dark moths on dark tree trunks in polluted woods, and they also pinned both types on lichen-covered tree trunks in unpolluted woods. They observed that birds ate more of the dark moths in the unpolluted woods (favoring the survival of the light-colored pattern), but birds in the polluted woods ate more of the light-colored moths, not the dark ones. These observations and the geographical patterns of variation (see Figure 5.5) were easily explained in terms of natural selection by predators. In addition, since the experiments wereGeographic variation in the frequency of melanic moths in the 1950s, which reached as high as 100% in polluted localities downwind from major industrial centers.0–30% melanics30–60% melanics60–80% melanics80–100% melanicsfirst conducted, laws to control smokestack emissions and other forms of pollution were passed and enforced, and many of the woods affected by pollution have returned to their former state. In these woods, the lichens have returned to the tree trunks, and most of the moths in these places again have the original light-colored pattern.Industrial melanism in insects demonstrates thatNThe melanic (black) variety and the original ‘peppered’ variety (below the right wing-tip of the melanic moth) on a light, lichen-covered tree trunk.major industrial centerThe same two varieties on a dark, soot-covered tree trunk.species can change in response to changes in the environment and were not created with permanent, unalterable traits. Lamarckian mechanisms fail to explain industrial melanism because, in these species, the adult colors do not change once they are formed, and there is nothing that individuals can do that would alter their color. The experiments with birds as predators clearly show natural selection at work.Evidence for branching descentDarwin’s contemporaries immediately recognized that his concept of “descent with modification” could be used to make sense out of a variety of observations not easily explained by other means. The branching pattern of descent explained the formation of groups or clusters of related species in particular geographic areas. Moreover, it explained the arrangement of these groups into a hierarchy of smaller groups within larger groups. Biologists before Darwin had been making classifications this way for about a century, but it was his theory of branching descent that explained why this type of classification made sense. Darwin predicted that biological classifications would increasingly become genealogies (that is, maps of descent similar to Figure 5.1) as more and more details about the evolution of each group of organisms became known. Darwin’s prediction came true as scientists found more and more evidence showing that relationships among species arise in branching patterns of descent. Evidence for such relationships comes from the comparative study of the anatomy, biochemistry, physiology, and embryology of different species.Homologies. The construction of family trees is based in large measure on the study of shared structures or gene sequences. Under Darwin’s paradigm, shared similarities are evidence that the organisms in question share a common ancestry. In a sense, a shared similarity is a falsifiable hypothesis that the several species sharing it are related to one another by descent. By itself, one such similarity reveals very little, but a large number of similarities that fit together into a consistent pattern strongly suggest shared ancestry. When the evidence for shared ancestry is compelling, the similarity is called homology.Darwin noted the similarities among the forelimbs of mammals: “what can be more curious than that the hand of a man, formed for grasping, that of a mole for digging, the leg of the horse, the paddle of the porpoise, and the wing of the bat, should all be constructed on the same pattern, and should include the same bones, in the same relative positions?” (Figure 5.6). Darwin wondered why similar leg bone structures appeared in the wings and legs of a bat, used as they are for such totally different purposes. Among the Crustacea (barnacles, crabs, shrimp, etc.), most species have a thorax region with eight pairs of leglike appendagesFigure 5.6Homologies among mammalian forelimbs adapted to different functions.HUMAN CHEETAH WHALE BAT used for locomotion, but the group that includes lobsters and crabs has the first three of these pairs modified into accessory mouthparts, leaving only five pairs of walking legs. Why, asks Darwin, should a crustacean that has more mouthparts have correspondingly fewer legs, or why should those with more legs have fewer mouthparts? Darwin’s answer is that all these structures arose by modification of the same type of repeated part. Crustacean mouthparts and legs are derived from a common set of leglike appendages. When the structure of these appendages varied (through mutation and other causes), natural selection favored different structures for different uses. Individuals with better-functioning mouthparts near the mouth, or with better-functioning legs near the center of gravity, left more offspring, and the proportions of the responsible genotypes increased in each population. As a consequence, when more appendages were used around the mouth as food-handling structures, there were fewer appendages remaining to be used as legs. An omnipotent God, however, could have added mouthparts without taking away legs (without being limited by the total number of appendages), leaving Darwin to declare, “How inexplicable are these facts on the ordinary view of creation!” (Darwin. Origin of Species, 1859, p. 437.)Vestigial structures. Structures whose function has been lost in the course of evolution tend to diminish in size. Often, they persist as small, functionless remnants, called vestigial structures. A good human example is the coccyx, a set of two or three vestigial tail bones at the base of the spinal column, homologous to the tails of other mammals. The Darwinian paradigm of natural selection and branching descent explains these vestigial structures as the remnants of structures that had once been functional. Neither Lamarck nor the creationists had any explanation for the presence of vestigial structures, and certainly not for the homologies of vestigial structures in many species with their functional counterparts in related species.Convergence. Similarities that result from common ancestry (that is, true homologies) should also be similar at a smaller level of detail, and even similar in embryological derivation, meaning that they should grow from the same source tissues. A hypothesis of homology can thus be falsified if two similar structures turn out to be dissimilar in detailed construction or in embryological derivation. There are also cases in which several hypotheses of homology are in conflict because they require different patterns of relationship for different characters. In such cases, evolutionists examine all the similarities more closely and repeatedly to see whether a reinterpretation is possible for one set of similarities.Convergence is an evolutionary phenomenon in which similar adaptations evolve independently in lineages not closely related. Similarities for which the hypothesis of homology is falsified by more careful scrutiny are often reinterpreted as convergent adaptations, meaning structures that evolved independently in unrelated lineages. Resemblance resulting from convergent adaptation is called analogy. Distinguishing homology from analogy is an ongoing aim of evolutionary classification. For example, the wings of bats and insects are analogous, rather than homologous, structures. They are constructed in different ways and from different materials, and their common shapes (which they also share with airplane wings) reflect adaptation to the aerodynamic requirements of flying. Although bat wings are not homologous toinsect wings, they are homologous to human arms, whale flippers, and the front legs of horses and elephants. These all have similar bones, muscles, and other parts in similar positions despite their very different shapes and uses, while insect wings have no bones and their muscles are very differently located.Cephalopods as an example. One frequent test of the hypothesis of branching descent is to identify a group of organisms that share some particular character, such as an anatomical or biochemical peculiarity. The general hypothesis of branching descent then gives rise to a more specific hypothesis, that these organisms all share a common descent from a common ancestor. An example of this type of reasoning can be illustrated by the Cephalopoda, a group of mollusks that includes the squids, octopuses, and their relatives. All cephalopods can be recognized by the presence of a well-developed head and a mantle cavity beneath (Figure 5.7). The mantle cavity contains the gills, the anus, and certain other anatomical structures. Other mollusks have mantle cavities, but only in the Cephalopoda is the mantle cavity located beneath the head and prolonged into a nozzlelike opening known as the hyponome. Knowing this, we can formulate the specific hypothesis that all cephalopods share a common descent.If our hypothesis is true, then we should be able to find, as evidence, some additional similarities among cephalopods not shared with other mollusks. Such similarities do exist: all cephalopods have beaklike jaws at the front of the mouth, and a muscular part, called the foot in other mollusks, subdivided into a series of tentacles (see Figure 5.7). Moreover,Figure 5.7Three living types of cephalopod mollusks (kingdom Animalia, phylum Mollusca, class Cephalopoda): the cuttlefish, the squid, and the chambered nautilus.CUTTLEFISH (Sepia) tentaclesshellCHAMBERED NAUTILUS (Nautilus)headhyponome gillmantle cavityjawsheadSQUID (Loligo) tentaclesheadeyetentacleshyponomemantle cavitygillshyponomegillmantle cavity all cephalopods have an ink gland that secretes a very dark, inky fluid. When a squid or octopus feels threatened by a predator, it releases this fluid into its mantle cavity and quickly squirts the contents of the mantle cavity forward through its nozzlelike hyponome. This action hides the animal and propels it backwards, in a direction not expected by its predator. The predator’s attention is meanwhile held by the puff of inky fluid. By the time the color dissipates, the squid or octopus has vanished. All members of the Cephalopoda have this elaborate and unusual escape mechanism, including squids, cuttlefishes, octopuses, and the chambered nautilus. The hypothesis of a common descent for all the Cephalopoda is thus consistent with the known data, meaning that the hypothesis has been tested and not falsified.Further comparisons among species. Since Darwin’s time, many additional types of similarities have been discovered among organisms. The comparative study of embryonic development has resulted in the discovery of many new similarities among distantly related species, some of which are described in Chapter 6. Comparative genomics (Chapter 4) and comparative studies in biochemistry have revealed the detailed structure of protein chains, DNA and RNA sequences, and other large molecules of biological interest. As with anatomical similarities, similarities in biochemistry or in embryology group related species together, and small groups are contained within larger groups at many hierarchical levels. Each new type of similarity has brought new evidence of branching descent with modification: in most cases, the groups established by older methods are reaffirmed when newer methods result in the same groupings. In a few cases, new groupings are discovered, and sometimes these are later corroborated by further evidence such as new fossil discoveries. On the basis of anatomical, embryological, and biochemical comparisons, hypotheses of common descent have been tested and confirmed for cephalopod mollusks and for many other groups of animals and plants. This increases our confidence in the larger hypothesis that all species of organisms have evolved from earlier species in patterns of branching descent. The many facts of comparative anatomy, comparative physiology, embryology, biogeography, and animal classification are all consistent with the hypothesis that modern species have evolved from ancestorsthat lived in the remote past, and they make little sense otherwise.Since Charles Darwin published his evolutionary ideas in 1859, thousands of tests have been made of his twin hypotheses of branching descent and natural selection. Because these thousands of tests have failed to falsify either hypothesis, both now qualify as scientific theories that enjoy widespread support. The Darwinian paradigm continues to this day as a major guide to scientific research.Further evidence from the fossil recordThe history of life on Earth is measured on a time scale encompassing billions of years. This geological time scale (Figure 5.8) was first established by studying fossils, the remains and other evidence of past life forms. Most fossils are formed from the burial of plants or animals in sediment. The soft parts of these organisms are often consumed or decomposed, but they may leave imprints in soft sediments if buried rapidly. Scientists had recognized since 1555 that most fossils were theremnants of species no longer living, thus providing clear-cut evidence for extinction. Comparisons of fossils with living species provide evidence of change over time and thus have a role in supporting the theory of descent with modification and the concept of evolution more generally.Stratigraphy. The geological time scale was first established through the study of layered rocks (stratigraphy). One of the first principles established in the study of these rocks was that when rock layers have not been drastically disturbed, the oldest layers are on the bottom and successively newer layers are on top of them. Using this principle, geologists can identify the rock formations in a particular place as part of a local sequence, arranged chronologically from bottom to top.Figure 5.8The geological time scale.THE WHOLE OF EARTH’S HISTORY MORE DETAILED VIEW OF PAST 550 MILLION YEARS millions of years ago055010002000300040004500millions of years ago065100200300400500550Figure 5.9Family tree of the class Cephalopoda (phylum Mollusca), showing branching descent over time. Horizontal width represents number of species in each group; vertical distance represents time.coiled curved straight noneLocal sequences from different places can be matched with one another in several ways, but the most reliable of these proved to be the study of their fossil contents. Two rock formations are judged to be from the same time period if they contain many of the same fossil species (the principle of correlation by fossils). The rocks do not need to be similar in composition or rock type—one can be a limestone and the other a shale—but if their fossil assemblages are similar, they are judged to be equally old. A single species of fossil is never sufficient; several fossil species are needed, and they must occur together with some consistency. Using this technique, paleontologists (scientists who study fossils) have been able to match up formations of the same age from many different localities, enabling them to assemble the world’s various local sequences into a ‘standard’ worldwide sequence, which is the basis for the complete sequence of time periods shown in Figure 5.8. The dates assigned to these periods are determined by measuring the rate of radioactive decay in certain rocks.Family trees. The age of a fossil, by itself, tells us very little about its place in any family tree. The relative ages of fossils only begin to have meaning when we study a group of organisms represented by many fossils. The family tree or genealogy of any group, called its phylogeny, fits into a pattern like that shown in Figure 5.1. Any such family tree is a hypothesis that biologists use to explain how the anatomical and other characteristics of each species are related, which leads to the classification of the group as a whole. In any family tree, the known fossils must fit into a consistent framework. living speciesoctopuses cuttlefishes chambered nautilusFor example, there aremany fossils of cephalopod mollusks, permitting further tests ofTertiaryOctopodaSepoidathe hypothesis of a common descent for all the Cephalopoda. Living and extinct cephalopodsCretaceousJurassic TriassicPermianPennsylvanianTeuthoidaBelemnoidaDIBRANCHIATAAMMONOIDEANautilidacan be arranged into a family tree consistent with our knowledge of the characteristics of each species and the relations among them (Figure 5.9). Differences among the living cephalopods can be explained with reference to this family tree. The chambered nautilus is very different from other livingcephalopods because it is fullyMississippianDevonian SilurianActinoceroidaOncoceroidaDisco-Ascoceroidahoused within a coiled shell and has four gills, while the squids and octopuses have only two gills and a very small, reducedEndoceroidaMichelino-ceroidasoroidashell or else none at all. Onewould therefore imagine a fam-OrdovicianCambrianN A U T I L O I D E AEllesmeroceroidaily tree in which octopuses and squids have a common ancestor that the chambered nautilus does not share. The fossilCephalopoda conform to these expectations. The group of cephalopods with the oldest fossil record is the nautiloids, of which the chambered nautilus is the only living remnant. A second group of cephalopods, called the ammonoids (see Chapter 18, p. 351), flourished in Mesozoic times, during the age of dinosaurs. A small, third group had an internal shell that became reduced in size. When the ammonoids became extinct, this third group, the Dibranchiata, persisted and is represented today by the squids and octopuses. Thus, the fossil record of the cephalopod mollusks, including both the anatomy and age relationships of fossil forms, confirms the relationships hypothesized on the basis of the anatomy of the living forms.The fossil record has repeatedly confirmed hypotheses of descent for particular living species. For example, Thomas Henry Huxley, one of Darwin’s early supporters, studied the anatomy of birds and declared them to be “glorified reptiles.” The interpretation of birds as descendants of the reptiles was strengthened by the discovery of Archaeopteryx, a fossil with many birdlike and also many reptilian features. Among these were a long tail, simple ribs, a simple breastbone, and a skull with a small brain and tooth-bearing jaws (Figure 5.10). Despite these reptilian features, Archaeopteryx had well-developed feathers and was probably capable of sustained flight. The discovery of transitional forms like Archaeopteryx, coupled with the fossils of other early birds and of feathered dinosaurs close to bird ancestry, strengthens our confidence in the hypothesis that birds evolved from reptiles. Other transitional forms are known, such as those between older and more modern bony fishes, between fishes and amphibians, between reptiles and mammals, and between terrestrial mammals and whales. Instead of being exactly intermediate in each trait, transitional forms usually exhibit a mix of some innovative characteristics and some ancestral characteristics.Post-Darwinian thoughtOne of the hallmarks of science is that hypotheses are subjected to rigorous and repeated testing. Darwin’s hypotheses have been thoroughly and repeatedly tested for nearly a century and a half, and the general outlines of branching descent and natural selection have been repeatedly and consistently confirmed. A second hallmark of science is that theories are extended and modified as new data are discovered. Here again, Darwin’s ideas have been extended and supplemented by newer findings. Many additional details are now known, none of which contradict the basic concepts of natural selection and branching descent. A third hallmark of a scientific theory is that it acts as a spur to further research, and Darwin’s two theories have stimulated more scientific research than just about any other theory in the history of biology, with the possible exception of Mendel’s theories in genetics. Evolution guides our thinking in nearly every field of biology, which is why “nothing in biology makes sense, except in the light of evolution.”During the period 1860–1940, scientists who doubted the effectiveness of natural selection proposed many other hypotheses to explain evolutionary change. Our modern theory of mutations originated from one such hypothesis. In Czarist Russia, scientists of nearly every political stripe (from conservative monarchists to socialists and anarchists) found the British idea of competition very distasteful. They were thereforeFigure 5.10The early bird Archaeopteryx, compared with a modernday pigeon. Modern birds lack teeth, and evolution has enlarged the braincase and strengthened other parts (wing, ribs, breastbone, pelvis, tail) highlighted here.reluctant to embrace the concept of natural selection, which they felt was based on a model of competition. (Darwin had emphasized that he meant competition in a “large and metaphorical sense,” but his Russian readers still found the similarity with capitalist economics distasteful.) As an alternative, the anarchist Petr Kropotkin, and the novelist and pacifist Leo Tolstoy, developed theories of “mutual aid” or mutualism as an important evolutionary mechanism. According to this view, organisms succeed (and leave more offspring) if they cooperate with one another instead of competing, as among social insects (see Chapter 8). Modern biologists now view mutualism as an adaptive interaction between species that may evolve as the result of natural selection. Natural selection favors any change that increases reproductive success, and this frequently includes changes that benefit other species directly. The theory of mutualism has thus been accepted into the mainstream of Darwinian evolutionary thought, and is no longer viewed as something incompatible with natural selection. Darwin himself gave several examples of cooperative interactions between species.Although Darwin’s theories of natural selection and branching descent continue to guide biological research to this day, the early 1940s saw the expansion of the evolutionary paradigm called the modern synthesis. Dar-braincasebraincasewing teethwingpelvis ribsribspelvistail tailbreastbone breastbone win’s ideas are retained in this expanded paradigm, but the findings of genetics are also incorporated and are used to explain the source of heritable variation. Natural selection is well documented as an important cause of evolutionary change, but it is by no means the only cause. Chance alone (accidents of sampling which individuals die, which live, and which reproduce) can cause erratic changes in the allele frequencies of natural populations, especially small ones. This phenomenon, called genetic drift, is discussed further in Chapter 7. The changes produced by genetic drift are usually nonadaptive, and they increase the chances that a small population will die out. Later in this chapter we will also discuss the importance of geographic isolation, a nonselective force that sets up conditions that bring about the evolution of new species.Beginning in the 1970s, Niles Eldredge and Stephen Jay Gould advocated a theory that they viewed as alternative to Darwinian thought. Darwin had frequently emphasized that evolutionary change was gradual, but Eldredge and Gould claimed instead that species remain static for long periods and then change abruptly. The new species begins, they said, as a small, isolated population on the geographic periphery of the original species. The small size of the isolated population allows it to undergo rapid change, producing a new species. Once the new species becomes successful, its numbers and geographic range may increase to the point where it invades the geographic range of the original species from which it evolved. If the new species successfully outcompetes the original one, the original one may become extinct. What we often see in the fossil record is the abrupt replacement of one species by another rather than a gradual change. Gould always claimed that this punctuated equilibrium theory is an alternative to Darwin’s gradualism, but certain other evolutionists (such as Ernst Mayr) view the two theories as fully compatible.For a family tree such as that shown in Figure 5.9, what kinds of fossil evidence (be specific) would falsify the descent pattern shown? What kinds of evidence would cause paleontologists to modify the family tree but continue to believe in aprocess of descent with modification? What kinds of evidence would falsify the hypothesis of descent with modification?One of the Galapagos finches studied by Darwin has woodpeckerlike habits and certain woodpeckerlike features: it braces itself on vertical tree trunks with stiff tail feathers in the manner of true woodpeckers and drills holes for insects with a chisel-like bill. However, it lacks the long, barbed tongue with which trueTHOUGHT QUESTIONSwoodpeckers spear insects; it uses cactus thorns for this purpose instead. How would Lamarck have accounted for this set of adaptations? How would Paley? How would Darwin? Which of these explanations accounts for the absence of the barbed tongue in the woodpecker finch? How would each hypothesis account for the absence of true woodpeckers on the Galapagos Islands?Is the study of evolution static or changing? Find some recent news articles dealing with new fossil discoveries or other new findings that deal with evolution.Explain antibiotic resistance in bacteria by using Darwin’s concept of natural selection.Creationists Challenge Evolutionary ThoughtOpposition to the idea that life evolves has come from various quarters. Many opponents of evolution have been creationists, people who believe in the fully formed creation of species by God. In this section we discuss a variety of creationist ideas, along with the creationist opposition to evolution.Creationists, by definition, believe that God created biological species. The majority of creationists believe that God created species much as we see them today, and that they did not evolve. Creationists are usually devout believers and most of them are Christian, but beyond these similarities creationists do not always share all of the same beliefs. Some creationists have been practising scientists who conduct research and follow scientific methodology, while others are strongly antiscience and may even seek the destruction of science and of scientific institutions.Three major groups of creationists stand out:Bible-based creationists, who insist on the biblical account of creation. These creationists work outside science and reject any scientific theory that conflicts with scripture; some of them are openly hostile to science.Intelligent-design creationists, who try to work within the framework of science to find evidence of design in nature. They claim that biological systems are so complex and so well adapted to their functions that only an intelligent (and benevolent) designer could have made them.Theistic evolutionists, who believe that God created the universe and all life, but that species evolved after that time and that evolution is one of God’s creative processes. Several practising scientists and various clergy adhere to this view.Bible-based creationismIn the United States, most creationists have based their beliefs on a literal interpretation of the Bible. Believing in the inerrant truth of their ideas, these creationists reject all science and all scientific evidence that contradicts their beliefs. Some of them are openly hostile to science. Almost all of these creationists are Protestant Christians, but they represent a small minority within the Protestant tradition. The large, established denominations accept the evidence for evolution as fully compatible with their religious beliefs.Various shades of opinion divide the Bible-based creationists into separate groups. One group, the ‘Young Earth’ creationists, insists that the six days of creation mentioned in Genesis were each 24 hours in length. Another group, the ‘Day–Age’ creationists, seeks to reconcile science with biblical accounts by proposing that the six days of creation should be interpreted as six ages of indefinite duration. (The Hebrew word ‘yom’ is often used this way elsewhere in the Bible.) Many mainstream clergy of various faiths subscribe to this view. Somewhat similar in their views are the ‘Gap’ creationists, who reconcile biblical with geological time scales by claiming that a long, indefinite gap of time intervened between the events described in Genesis chapter 1 and Genesis chapter 2.Early fundamentalism. In the early twentieth century, most opposition to evolution came from certain Protestants, mostly in the United States, who declared that evolution conflicted with the account of creation given in the Bible. These people founded a number of societies, including the Society for Christian Fundamentals (the origin of the term fundamentalist). The fundamentalists persuaded several state legislatures to pass laws restricting or forbidding the teaching of evolution in schools. Some of these state laws remained until the 1960s.In 1925, a famous court case was brought in Tennessee by the fledgling American Civil Liberties Union. A teacher, John H. Scopes, was arrested for reading a passage about evolution to his high school class. The trial attracted worldwide attention. Scopes lost and was assessed a$100 fine. Upon appeal, the case was thrown out because of the way in which the fine had been assessed; the merits of the case were never really debated. The Scopes trial did, however, have a chilling effect on the textbook publishing industry: books that mentioned evolution were revised to take the subject out, and most high school biology textbooks published in the United States between 1925 and 1960 made only the barest reference, if any, to Charles Darwin or any of his theories.Creationism in recent decades. The Soviet launch of the Earth-orbiting satellite Sputnik in 1958 set off a wave of self-examination in American education. Groups of college and university scientists began examining high school curricula with renewed vigor, and several new high school science textbooks were written. Most of the new biology texts emphasized evolution, or at least gave it prominent mention.Alarmed in part by the new textbooks, a new generation of creationists began a series of attacks on the teaching of evolution. These new creationists tried to portray themselves as scientists, calling their new approach ‘creation science’ even though they never conducted experiments or tested hypotheses. Instead of making their studies falsifiable, the new creationists claimed that they held the absolute truth:Biblical revelation is absolutely authoritative…. There is not the slightest possibility that the facts of science can contradict the Bible and, therefore, there is no need to fear that a truly scientific comparison…can ever yield a verdict in favor of evolution…. The processes of creation…are no longer in operation today, and are therefore not accessible for scientific measurement and study. (H.M. Morris (Ed.). Scientific Creationism. San Diego: Creation- Life Publishers, 1974, pp. 15–16 and 104.)We do not know how the Creator created, what processes He used, for He used processes which are not now operating anywhere in the natural universe…. We cannot discover by scientific investigations anything about the creation process used by the Creator. (D.T. Gish. Evolution: The Fossils Say No!. San Diego: Creation-Life Publishers, 1978, p. 40.)In contrast, Darwin knew that his theories were—rightly—subject to empirical testing and possible falsification (see the quotation on page 147).Some creationist writings contain faulty explanations of scientific concepts. One such misinterpretation uses the second law of thermodynamics. According to this law, a closed system (one in which energy neither leaves nor enters) can only change in one direction, to that of less order and greater randomness. Thus, a building may crumble into a pile of stones, but a pile of stones cannot be made into a building without the expenditure of energy. Creationists have claimed that this law precludes the possibility of anything complex ever evolving from something simpler. The second law of thermodynamics does not, however, rule out the building up of complexity; rather, it states that making something complex out of something simple requires an input of energy. The second law of thermodynamics does apply to all biological processes. If the Earth were a thermodynamically closed system, life itself would soon cease. However, the Earth is not a thermodynamically closed system because energy is constantly being received from the Sun, and this energy allows life to persist and evolve. Creationist claims on this point may have originated as an innocent error, but the point has been so well refuted that its continued use can only be a deliberate misrepresentation that lies outside the bounds of science or of honest debate.In the 1960s, because many of the laws in the United States forbidding the teaching of evolution had been declared unconstitutional, one group of creationists, led by Henry Morris, Duane Gish, and John Slusher, decided on a new approach. Evolution could be taught in the schools, they argued, but only if ‘creation science’ was taught along with it and given equal time. (The concept of ‘equal time,’ was originally a measure to ensure fairness in political campaigns.) A few state legislatures passed laws inspired by this new group of creationists. An Arkansas law known as the Balanced Treatment Act (Public Law 590) was finally declared unconstitutional in 1981, and a similar Louisiana law was declared unconstitutional a few years later. Interestingly, in the challenges to these laws, the scientific issues were raised in court, and prominent scientists were called upon to testify. Specifically, in the Arkansas and Louisiana cases, the U.S. Court of Appeals was asked to rule on what is scientific and what is not. The court finally ruled that evolution is a scientific theory and may be taught, whereas ‘creation science’ is not science at all because it involves no testing of hypotheses and because its truths are considered to be absolute rather than provisional. Instead, ‘creation science’ was found to be a religion, or to include so many religious concepts (creation by God, Noah’s flood, original sin, redemption, and so forth) that it could not be taught in a public school without violating the U.S. Constitution’s historic separation of church and state.In the 1990s, a new group of creationists emerged, advocating the view that modern science, particularly evolution, is the basis for the materialistic philosophy that they claim is responsible for all that is wrong in today’s society. The avowed aim of this group, called the ‘Wedge group’, is to destroy all of science, and evolution in particular, by driving in a thin ‘wedge’ and then continuing to drive it in deeper and deeper until the body of science is split asunder. Small but well-financed, this group is the guiding force behind the Discovery Institute and the Center for the Renewal of Science and Culture (CRSC), both of which support intelligent-design creationism.Creationists continue to exert influence today. Despite state laws that have been declared unconstitutional, creationists continue to pressure local school boards and state education departments to support their approach. These efforts have sometimes been successful. In 1999, the Board of Education in Kansas approved, at the urging of creationists, a statewide science curriculum that included no mention of evolution. They also approved a statewide program for testing scientific knowledge and understanding, but decided that an understanding of evolution should not be part of this testing program. Two years later, after two of the officials who had voted for this curriculum had been voted out of office and a third had left voluntarily, the Board of Education reversed its earlier decision and restored evolution to the science curriculum in Kansas. This kind of opposition to the teaching of evolution is largely an American phenomenon. Biologists in most countries other than the United States have not faced similar opposition.Intelligent designIn the eighteenth and nineteenth centuries, many creationists were also scientists who proposed and tested hypotheses. For example, Reverend William Paley and his supporters proposed that biological adaptations were the work of a benevolent God. In 1996, American biochemist Michael Behe resurrected Paley’s preevolutionary arguments and revised them in the new language of cell biology and biochemistry.Paley’s Natural Theology. Paley sought to prove the existence of God by examining the natural world for evidence of perfection in design. The anatomical structures examined by Paley and his supporters were so well suited to the functions that they served and were, in his view, so perfectly designed that they could only have come from God. Paley’s school of Natural Theology was very influential in Britain in the early nineteenth century, and the young Charles Darwin was educated in its lessons.Paley and his supporters had paid much attention to complex organs such as the human eye. The eye, they pointed out, was composed of many parts, each exquisitely fashioned to match the characteristics of the other parts. What use would the lens be without the retina, or the retina without a transparent cornea? An eye, they argued, would be of no use until all its parts were present; thus it could never have evolved in a series of small steps, but must have been created, all at once, by God.Paley pointed to the structure of the heart in human fetuses as containing features that adaptation to the local environment could not account for. In adult mammals, including humans, the blood on the left side of the heart is kept separate from the blood on the right side of theheart (see Chapter 10, pp. 353–354). In fetal mammals, the blood runs across the heart from the right side to the left, bypassing the lungs, which are collapsed and nonfunctional before birth. As the blood enters the left side of the heart, it passes beneath a flap that is sticky on one side. When the baby is born, its lungs fill, and blood flows through them. The blood returning to the heart from the lungs now builds up sufficient pressure on the left side that the flap closes. Because it is sticky on one side, it seals shut. No amount of adaptation to the environment, said Paley, could endow a fetus with a valve that was sticky on one side so that it would seal shut at birth. Only a power with foresight could have realized that the fetus would need a heart whose pattern of blood flow would change at birth, and thus designed the sticky valve. Paley attributed the foresight to God, and he insisted that no other hypothesis could explain such an adaptation to future conditions.What is most interesting is that Paley and his many supporters understood the nature of science and used the methods of science to argue their case. Paley in particular sought scientific proof of God’s existence and benevolence by arguing that no other hypothesis could explain the evidence as well. This example shows that good science is certainly compatible with a belief in God or a rejection of evolution. In fact, the best scientists of the period from 1700 to 1859 were, with few exceptions, devout men who rejected the pre-Darwinian ideas of evolution on scientific grounds.Darwin’s response. Darwin was quite familiar with Paley’s arguments, and he offered evolutionary explanations for many of the intricate and marvelous adaptations that Paley’s supporters had described. In each case, Darwin argued that the hypothesis of natural selection could account for the adaptation as well as the hypothesis of God’s design.To counter Paley’s argument about complex organs such as the eye, Darwin pointed out that the eyes of various invertebrates can be arranged into a series of gradations, ranging in complexity from “an optic nerve merely coated with pigment” to the elaborate visual structures of squids, approaching those of vertebrates in form and complexity. A large range of variation in the complexity of visual structures is found within a single group of organisms, the Arthropoda, which includes barnacles, shrimps, crabs, spiders, millipedes, and insects. All the visual structures, regardless of their degree of complexity, are fully functional adaptations, advantageous to their possessors. It would therefore be quite reasonable, argued Darwin, to imagine each more complex structure to have evolved from one of the simpler structures found in related animals. Eyes, in other words, could have evolved through a series of small gradations.As an additional argument against Paley, Darwin also pointed out several adaptations that were less than perfect, or that seemed to be ‘making do’ with the materials at hand. The gills in barnacles are modified from a brooding pouch that once held the eggs. The milk glands of mammals are modified sweat glands. The giant panda, evolved from an ancestor that had lost the mobility of its thumb, developed a new thumblike structure made from a little-used wrist bone. (This last example was not known in Darwin’s time, but fits well into his argument.) These many adaptations seem more easily explained by natural selection than by God’s design because the design is imperfect and God could presumably have ‘done better.’ Natural selection is limited to the use of the materials at hand, and then only if there is variation; an omnipotent God could have made barnacle gills from entirely new material without taking away the brood pouches, and could have given pandas a true thumb instead of modifying a wrist bone. Darwin and his supporters used examples like these to show that the evolutionary explanation fitted the available evidence better than Paley’s explanation of divine planning. For example, natural selection perpetuates only those hearts whose flaps seal properly at birth.‘Irreducible complexity.’ With today’s knowledge of cell biology and biochemistry has come a return to Paley’s argument from design at the molecular level. The major proponent of this argument is biochemist Michael Behe. He begins with the claim that every living cell contains many sophisticated molecular systems that he calls “irreducibly complex.” An irreducibly complex system, according to Behe, is any system that is nonfunctional unless all of its parts are present and functional. Behe’s argument, which echoes Paley’s, is that no irreducibly complex system could evolve by small, piecemeal steps. According to this creationist argument, natural selection can only improve upon a functioning system, so could never create a system that requires many parts in order to function at all. Thus, if a complex system cannot function without a minumum of five components, then natural selection could never bring about the evolution of a second component when only one existed, or a third component when only two existed, because none of these changes would improve anything if the system remained nonfunctional with fewer than all five of the required components. Paley had earlier made the same argument with regard to the several parts of the eye, as did the British zoologist St. George Mivart in Darwin’s time. Darwin himself realized the power of this argument, for he wrote:If it could be demonstrated that any complex organ existed, which could not possibly have been formed by numerous successive, slight modifications, my theory would absolutely break down. (Darwin. Origin of Species, 1859, p. 189.)There are at least two responses to counter the argument of irreducible complexity. One is to show that the system is not, in fact, irreducibly complex, and that a partial system with only one or a few of its components does function in some capacity and represents an improvement over the same system with fewer components or none at all. If one component is an improvement over none, and two are an improvement over one, then the entire system can evolve piecemeal, step by step, because each step is an improvement over the previous ones, and natural selection favors each small, successive change.The other response to irreducible complexity is to recognize the role played by changes in function. A system may be incapable of its present function unless fully formed, and thus be described as irreducibly complex. However, the system, or some of its parts, may originally have served a different function, and thus could have evolved by a series of small steps as long as each step improved some ability to serve some function. This can be illustrated by the evolution of insect wings, which developed from external folds of the thoracic wall. By building models of insects with no folds, tiny folds, medium-size folds, and folds large enough to function as wings, scientists were able to show that an increase in the size of the fold from none to small or from small to medium would hardly have improved flying ability. Natural selection would probably not have been able to bring about the early increases in the size of the folds, based upon their usefulness in flying. On the other hand, the function of the folds in cooling the body was also considered. Muscular activity generates heat, and an animal would be in danger of cooking its own tissues if it exercised vigorously without somehow dissipating heat. The efficiency of the flaps in cooling the body also varies with size, as shown in Figure 5.11. Most of the improvement comes in the smaller sizes, with medium flaps dissipating more heat than small ones, which in turn dissipate more heat than noneFigure 5.11The evolution of insect wings. The efficiency of thoracic folds in primitive insectlike arthropods was measured according to two criteria: efficiency in cooling the body down by dissipating heat, and efficiency in airborne locomotion by adding to downward air resistance and to lift. Up to a certain size, increments in the size of the folds improved cooling ability but had little effect on locomotion. Thus, early increases in fitness among small to moderate wing sizes depended on improved cooling; however, later increases in fitness depended more on improvements in flying ability.at all. Large flaps, on the other hand, are scarcely any more efficient than medium-size flaps in their cooling ability. Thus, the early stages in the evolution of the wing flaps are thought to have been selectively favored because they improved the body’s ability to exercise more without overheating. Only after the flaps had reached a certain medium size, their function as wings became more important than their function in dissipating heat. Thus, the early stages were selectively improved because they helped dissipate heat, while the later stages were selectively improved because they functioned as wings.As this example shows, the early stages in the evolution of a structure may have been useful for a totally different function than the one they now serve. Half-built structures, or systems with only a few components, may have improved the ability of their possessors to pass on their genes even without fulfilling their present function. Many structures are now known to have changed their function in the course of evolution.With these evolutionary counter-arguments in mind, we can now examine Michael Behe’s claims of irreducible complexity for several systems that function within cells. All of them could have evolved gradually, step by step, despite Behe’s insistence to the contrary. For example, the clotting of blood is a multi-step process that Behe argues is “irreducibly complex” because none of it would work unless all of it were present. In fact, blood can clot upon exposure to air, and the many chemicals that improve clotting ability could certainly have evolved one at a time, each representing a piecemeal improvement. Natural selection would favor the evolution of any protein or other compound that aided in the clotting process and reduced the chances of bleeding to death. Because blood chemistry does not fossilize, we have no proof of how blood clotting evolved, but a gradual evolution is certainly plausible.Another of Behe’s examples discusses complement proteins and antibody production. A somewhat detailed explanation of how this systemworks, and how various parts of the system can and do function apart from the rest, can be found on our Web site (under Resources: Complement). If parts of the system are useful without the remainder (and, in fact, functional in species known to lack the complete system), then they certainly could have evolved in small steps by natural selection.Conclusions. It is important to note that Behe has conducted no research and provided no scientific evidence to support his claims of irreducible complexity or to test any other hypothesis. Perhaps we should describe his claims as philosophical rather than scientific. One importantNONE SMALL INTERMEDIATE LARGEsize of wing flapsmeasure of a scientific theory is the amount of research that it stimulates. Behe’s concept of irreducible complexity has stimulated no research that supports any of his claims, but many arguments have been offered to show that the systems that Behe discusses are not, in fact, irreducibly complex.All of the systems that Behe claims to be irreducibly complex can be explained as the products of gradual, step-by-step evolution, especially if changes in function are considered. Various biologists have examined Behe’s claims and none, to our knowledge, support them. Of the systems that Behe describes, none withstands scrutiny as an argument against evolution.Despite the many criticisms that have been raised against Behe’s arguments, the state of Ohio in 2002 seriously considered a proposal to add intelligent design to the science curriculum as an alternative to evolution by natural selection, even though there is no evidence (produced by hypothesis testing) to support the idea. Irreducible complexity is not a scientific theory, and does not qualify as science in the minds of most scientists.Reconciling science and religionA majority of scientists are religious, and a majority of devout people of all religions also accept scientific findings. There are many ways of reconciling religious and scientific viewpoints, and a majority of theological seminaries of all faiths teach that science and religion are fully compatible. The following are examples of the ways in which some people have reconciled religious beliefs and science.René Descartes was the originator of a dualistic philosophy that separates science and religion as operating in different spheres. In this view, science informs us about the physical world, including the human body, while religion informs us about the spiritual world, including both God and the human soul. Questions about the body can be answered by science, while questions about the soul or about God can be answered only theologically. A separation between science and religion, based on this dualism, has become the official view of the Roman Catholic Church.The Protestant theologian Reinhold Niebuhr defines religion as the study of the “ultimately unknowable.” In this view, advances in science have expanded the frontiers of knowledge—the study of what is knowable, but religion is the study of what remains—the ultimately unknowable. Thus, religion and science operate in separate spheres, and there is no possibility of an incompatibility between them.Various scientists have expressed the view that God should be excluded from scientific theories whenever it is possible to do so. One such scientist was the early nineteenth century French astronomer and mathematician Pierre Simon LaPlace, one of the authors of the idea that galaxies and solar systems form from swirling masses as the result of natural gravitational forces. When he published his book on this ‘nebular hypothesis,’ he presented a copy to the emperor Napoleon, who asked him why he had not mentioned God in his book. LaPlace replied, “I have no need of that hypothesis.” A similar attitude caused the British geologist Charles Lyell to exclude all miracles from his geological theories.According to some twentieth-century versions of a theory called ‘operationalism,’ God’s presence in certain scientific explanations may not be needed. Thus, the statement, “The Grand Canyon was formed by the action of running water over long periods of time” is indistinguishable from the statement, “God formed the Grand Canyon by the action of running water over long periods of time.” Any evidence that could support either of these statements would also support the other, and any evidence against either statement would also be evidence against the other. The two statements are operationally equivalent (or indistinguishable) because no evidence could possibly distinguish between them. According to this view, God is not a necessary part of the explanation, in line with the view that LaPlace had expressed earlier.A number of scientists and religious thinkers have reconciled science with their religious beliefs by accepting the findings of science as an explanation of the ways that God operates. God created the world along with the natural laws that govern it, and science attempts to discover these natural laws. Isaac Newton, William Paley, and Albert Einstein all expressed views along these lines. One version of this approach is that God set natural laws in place but then withdrew to allow the universe to unfold according to the workings of these natural laws. Another version is that God occasionally intervened to set things right by making exceptions to natural laws. Einstein, who favored the non-interventionist interpretation, ridiculed this second approach in his statement, “I can’t believe that God plays dice with the world.”Theistic evolution represents an attempt along these lines to reconcile evolution with a creationist viewpoint, either with or without divine intervention. The Jesuit philosopher and paleontologist Pierre Teilhard de Chardin believed that evolution, including human evolution, was part of God’s method of creation in accordance with natural law. Charles Lyell, a geologist who had inspired Darwin’s early thinking, and Alfred Russell Wallace, a naturalist who discovered natural selection independently of Darwin, both came late in life to the belief that evolution was the consequence of natural laws, but that divine intervention had been necessary to bring about the evolution of human beings. Most scientists, however, see no need for any such exceptions to explain human evolution.THOUGHT QUESTIONSIn what ways did William Paley use scientific evidence? Did he use testable hypotheses? Which of today’s creationists use falsifiable hypotheses to support their claims?How much time should be devoted in science classes to alternative explanations or theories that have been tested and rejected? Should time be given to explanations that are not testable? Should all explanations be given equal time? How much (if any) of a science curriculum would you devote to divine creation as an alternative to evolution? To astrology as analternative to astronomy? To the theory that disease is caused by demons or evil spirits?Does the teaching of unpopular or rejected theories encourage students to think critically? Does it encourage attitudes of fairness? Does it increase students’ understanding of what science is and how science works?Do you think that the concept of intelligent design should be taught in high schools asan alternative to evolution by natural selection? Why or why not?Species Are Central to the Modern Evolutionary ParadigmThe evolutionary paradigm known as the modern synthesis was based largely on the fusion of genetics with Darwinian thought. The cornerstone of the modern synthesis paradigm is a theory of speciation, the process by which one species branches into two species.Populations and speciesA biological population consists of those individuals within a species that can mate with one another in nature. If we look backward in time, we realize that any two individuals in a population share at least some of their alleles because of common descent. If we look into the future, we see that any two opposite-sex individuals in a population are potential mates. Membership in a population is determined by descent and by the capacity to interbreed.Biological populations within a species may exchange hereditary information (alleles) with one another. The combining of genetic information from different individuals or the exchange of genetic information between populations is called interbreeding. The existence of biological barriers to such exchange is called reproductive isolation. Interbreeding between populations of the same species takes place when members of different populations mate and produce offspring; reproductive isolation inhibits such matings to varying degrees.Species are defined as reproductively isolated groups of interbreeding natural populations. There are several points to note in this definition. Physical characteristics (morphology) are not part of the definition of species; species are defined by breeding patterns instead. Populations belonging to the same species will interbreed whenever conditions allow them to. Populations belonging to different species are reproductively isolated from one another and will thus not interbreed. Any biological mechanism that hinders the interbreeding of these populations is called a reproductive isolating mechanism, as explained below. Species are composed of natural populations, not of isolated individuals. Thus, the mating behavior of individuals in captivity can only serve as indirect evidence of whether natural populations would interbreed under natural conditions.The many reproductive isolating mechanisms fall into two broad categories: those that prevent matingand those that interfere withFigure 5.12Reproductive isolation of several frog species by season of mating, an ecological means of preventing mating between development after mating has occurred. Mating is prevented when potential mates never encounter each other, possibly because they live in different habitats, or because they are active at different times of day or in different seasons, or because they are not physiologically capable of reproduction at the same time. Figure 5.12 shows that wood frogsmaximumnoneMar 1Apr 1May 1timeJun 1Jul 1Aug 1Figure 5.13Flashing patterns used as mating signals by different species of fireflies. The species 1 to 9 are reproductively isolated from one another by the behavioral differences shown in these patterns.Details in this form of behavioral isolation include the duration of each flash, the number of repetitions, and the location of the insect when it flashes. A firefly will respond only to the flashing pattern of its own species.1are fully isolated ecologically from tree frogs and bullfrogs by breeding at different seasons; they are partly isolated from pickerel frogs because the breeding seasons overlap only slightly. Mating can also be prevented by differences in behavior, allowing potential mates with different courtship rituals to live together in the same place without mating. For example, different species of fireflies (phylum Arthropoda, class Insecta, order Coleoptera, family Lampyridae) use different flashing patterns and flight patterns (Figure 5.13) as mating signals. In addition, insects and some other animals have hardened and inflexible sexual parts (genitalia); mating of these animals requires a ‘lock and key’ fit, and mating is prevented if the parts do not fit together properly.There are other isolating mechanisms in which mating occurs butthe offspring do not develop. In animals, sperm from a male of another species may die before fertilization takes place. In plants, the pollen may fail to germinate on the flowers of another species. If a mating takes place between species, the fertilized egg may die after fertilization. Incompatible chromosomes may disrupt cell divisions and developmental rearrangements, leaving the embryo or larva to die. Alternatively, hybrid individuals may live for a while but not reach reproductive age, or they may be sterile. For example, a mule is a sterile hybrid between a horse and a donkey. The sterility of mules keeps the gene pools of horses and donkeys separate, so they remain separate species.How new species originateTo explain how a new biological species has come into existence, we need to explain how it has become reproductively isolated from closely related species. The origin of a species is thus the origin of one or more repro-ductive isolating mechanisms.In the vast majority of cases, new species have come into existence through a process of speciation that includes a period of geographic isolation in which populations are separated by some sort of barrier such as a mountain range or simply an uninhabited area that the organisms do not cross. The essence of the theory is that reproductive isolating mechanisms originate during times when such barriers separate populations geographically. Geographic isolation is not by itself considered to be a reproductive isolating mechanism; rather, it sets up6 the conditions under which the separated populations may evolve along different lines, resulting in7 reproductive isolation.What happens depends in part on the length oftime for which the populations are geographicallyisolated—more time allows more chances for reproductive isolating mechanisms to evolve. Another factor is that natural selection must favor differenttraits on the two sides of the geographic barrier. That is, conditions must be different enough for oneset of traits to increase fitness in one locale and for adifferent set of traits to increase fitness in anotherlocale. If the populations on opposite sides of the barrier are selected differently for a long enough period, then one or more reproductive isolating mechanisms may evolve between the two groups of populations and separate them into different species (Figure 5.14). If the populations later come into geographical contact again, the reproductive isolating mechanisms that have evolved during their separation will keep them genetically separate as two species. For example, frog or cricket populations isolated on opposite sides of a mountain chain or a large body of water may develop different mating calls. Because the animals respond only to the mating calls of their own population, the two populations will be reproductively isolated and thus become separate species.The geographic theory of speciation predicts that examples of incomplete speciation may be discovered. If two populations are separated for a very long time (or if selective forces on opposite sides of a barrier differ greatly), then the populations are likely to split into two species. If the separation is brief, then speciation is unlikely. These two situations lie at opposite ends of a continuum. Somewhere along this continuum lies the situation in which populations have been separated by a geographic barrier long enough for reproductive isolation to begin evolving, but not yet long enough for the reproductive isolation to be perfected. Partial or imperfect reproductive isolation between two populations would lessen the chances of interbreeding between them, but not prohibit it entirely. Such situations have indeed been found, for example, among the South American fruitflies known as Drosophila paulistorum. Crosses between divergent populations of Drosophila paulistorum produce fertile hybrid females but sterile hybrid males. The geneticists studying these flies referred to them as “a cluster of species in statu nascendi” (in the process of being born).People intuitively group similar species together and give names to many collective groups: birds, snakes, insects, pines, orchids, and so forth. Biologists organize these collective groups into a classification that reflects the degree of evolutionary relatedness among species, using methods described in Chapter 6.Figure 5.14Geographic speciation: the evolution of reproductive isolation during geographic isolation. Genetically variable populations that spread geographically can develop locally different populations that are capable of interbreeding with one another initially. If the populations are separated for a long enough time by a barrier such as a mountain range or a deep canyon, they may develop differences that prevent interbreeding even after contact is resumed. past presentgeographic speciationInitial population has lots of genetic variationMountain range arises, separating population into two groupsEnvironment becomes different on the two sidesTwo populations diverge as mutation and selectionfit organisms to environmentWhen populations come into contact again, reproductive isolating mechanisms keep species genetically separateTHOUGHT QUESTIONS1 What kinds of reproductive isolating mechanisms might prevent related species of antelopes from interbreeding? Answer the same question for related species of birds, related species of trees, and related species of butterflies.2 Several kinds of organisms reproduce asexually, producing offspring without combining gametes from two parents. Can asexually reproducing organisms belong to species? Can the definition of species be modified to apply to asexually as well as sexually reproducing organisms?Life on Earth Originated by Natural Processes and Continues to EvolveIn addition to explaining how species change and how new species arise, modern evolutionary theory also accounts for the origins of life on Earth. The origin of life, the early history of life on Earth, and the effects of life on Earth’s atmosphere will all be discussed in Chapter 19.Evolution as an ongoing processEvolution is a process that takes place within species as well as between species, and the process continues in the present as it has in the past. The evolutionary changes in populations and the changes that create new species can be studied as they occur. Within the twentieth century, the peppered moths of some locations in England changed from predominantly light-colored to almost all dark and back again. In one species of Galapagos ground finches, Geospiza fortis, the average bill size changes back and forth. Small-beaked birds that eat soft seeds survive and produce the most offspring in years when rainfall is adequate, but birds with larger beaks are at an advantage in drought years because they can open large, tough old seeds. The average bill size of birds within the population thus increases in drought years and decreases in wet years. In fruitflies, different chromosomal variations (inversions) are favored in different seasons. We see that evolution responds adaptively to fluctuating environmental conditions. Different alleles are selected by different environmental conditions at different times because their phenotypes are more adaptive in those conditions.Selection also continues to operate in human populations and in bacteria. For example, infant mortality is much higher among babies born under about 3 kg (7 lb) in weight, even with all that modern medicine can offer. Natural selection thus favors birth weights close to this optimum value. Selection also favors certain human genotypes in certain environments (Chapter 7) and during epidemics (Chapter 17). The use of antibiotics has favored the evolution of resistance to these drugs among bacteria (Chapter 17).Concluding RemarksConsiderable evidence now shows that evolution has taken place in the past and that organisms continue to evolve today, though often slowly. The ways in which species resemble one another and are related to one another reflect branching patterns of descent. Evolutionary change is brought about by natural selection, a process that operates whenever some genotypes leave more offspring than others. Species are reproductively isolated from one another, and the splitting of a species therefore requires the evolution of a new reproductive isolating mechanism. All species, including humans, arose by speciation and are products of evolution. Our attempts to classify the resulting diversity of species are explained in Chapter 6.Chapter SummaryEvolution is the central, unifying concept of biology.Darwin’s major contributions included his theories of branching descent(“descent with modification”) and natural selection.Only inherited traits contribute to evolution and bring about adaptation; acquired characteristics do not.Evolution operates through natural selection: there is heritable variation in all species, and different genotypes differ in fitness by leaving different numbers of surviving offspring.Forces of natural selection include predators, disease, and sexual selection.Mimicry is easily explained by natural selection but not by any alternative hypothesis.Branching descent with modification accounts for homology between species. Fossils provide important evidence for evolution, as does the comparative study of anatomy, biochemistry, and embryological development.The modern synthesis combines Mendelian genetics with Darwinian evolution. It describes the evolution of genes and phenotypes in populations, and it includes a theory for the formation of species through geographic isolation.Speciation occurs through the build-up of genetic differences between populations arising primarily during times of geographic isolation. Over time, this results in reproductive isolation, which prevents interbreeding between species.Evolution continues today in all species. In many cases, we can detect ongoing change from year to year.CONNECTIONS TO OTHER CHAPTERSChapter 1 Darwinian evolution and modern evolutionary theory are both good examples of successful paradigms.Chapter 1 Presenting creationist ideas in school classrooms raises several social policy issues.Chapter 2 Gene mutations provide the raw material for evolution.Chapter 4 Comparative genomics reveals evolutionary patterns of descent.Chapter 6 Branching descent and other evolutionary processes have produced a great diversity of species that have been described and classified, and many others that await discovery and description.Chapter 7 Differences have evolved and continue to evolve both within and among human populations.Chapter 8 Social behavior and reproductive strategies are, in part, products of evolution.Chapter 9 Successful species may increase so rapidly in numbers that they outstrip the available resources.Chapter 11 Plant characteristics resulting from evolution include the presence of chloroplasts and vascular tissues.Chapter 13 Differences in brain anatomy in different species provide good evidence of evolution.Chapter 16 Viruses and other microorganisms may evolve disease-causing strains, as well as strains resistant to certain medicines.Chapter 17 Bacteria often evolve antibiotic resistance through natural selection.Chapter 18 Speciation increases biodiversity, whereas extinction diminishes biodiversity.Chapter 19 The evolution of life has changed the entire Earth, including the atmosphere and all habitats.PRACTICE QUESTIONSMatch the ideas in the first list with the people in the second. One name needs to be used twice.Evolution is a branching process.Adaptations should be studied carefully as a way of understanding God’s creation.Evolution should never be taught.New species originate by a process that includes geographic isolation.Adaptation occurs by use and disuse.Organisms with successful adaptations will be perpetuated, whereas those with unfavorable characters will die out.Evolution and creation science should be given equal time in science classes.Creationist supporters of the ‘balanced treatment act’Creationists of the period 1890–1940Charles DarwinJean Baptiste LamarckWilliam PaleyModern evolutionary biologistsThe Bahamas are a group of islands in the Atlantic, made mostly of coral fragments. The closest mainland is North America, but political ties are to Great Britain. According to Darwin’s reasoning, the birds and other species living on these islands should have their closest relatives in:other islands of similar composition in the Pacificislands such as the Canary Islands, in the Atlantic at a similar latitudeNorth America
England
What theory failed to explain the sticky valve in the fetal heart?
Darwin
palettes
Lamarcks
In mimicry, the mimics and their models always:live in similar climates, although they may be far awaylive close togethertaste the same to predatorsare camouflaged to resemble their backgroundsWhich of these is NOT considered a reproductive isolating mechanism?two geographically separated speciestwo species breeding in different seasonstwo species that produce infertile hybrids when they matetwo species with different mating callstwo species whose external genitalia cannot fit togetherGive a clear definition of the term species.What is the basic argument used by supporters of intelligent design? What kinds of evidence can be used against this argument?Taylor & FrancisTaylor & Francis Group important?IssuesWhy is life so diverse?Why have some groups proliferated into so many species?Why is classification6Chapter OutlineWhy Classification Is Important“All those names” Taxonomic theoryModern Classifications Recognize aHow do our classifications reflect evolution?How are classifications established?Did humans evolve? How and why? Where and when?Evolution (adaptation, descent with modification)Form and functionSpecies and speciationProducts of evolutionary change (phylogenetic classification, biodiversity)Types of cells (procaryotic, eucaryotic)Hierarchy of organizationClassification of organisms (three domains and six kingdoms)Sexual recombinationMajor groups of organismsPlant structure and adaptations (vascular tissues, seeds, flowers, etc.)Animal structure and adaptations (bilateral symmetry, sense organs, head, assembly-line digestion, body cavities, segmentation, etc.)Great Difference Between Procaryotic and Eucaryotic CellsProcaryotic cells Eucaryotic cellsEndosymbiosis and the evolution of eucaryotesSix Kingdoms of Organisms Are Included in Three DomainsDomain and kingdom Archaea Domain and kingdom Eubacteria Domain EucaryaKingdom Protista Kingdom Plantae Kingdom Mycota Kingdom AnimaliaHumans Are Products of EvolutionOur primate heritage Early hominidsThe genus Homo159160Classifying Natureife on Earth is extremely diverse, with an estimated 10 million species or more. Why is life so diverse and so prolific? How do we describethis diversity? How can we begin to understand it? As Charles Darwin observed, every living species has so great a tendency to reproduce that, if left unchecked, there would soon be no standing room left on Earth for all its progeny. As we saw in Chapter 5, species can also undergo speciation: splitting and thus creating additional species. This process has been going on so long and so frequently as to have produced the many millions of species alive today, plus an even greater number of species that have become extinct in the past. In this chapter we will point out certain innovations that greatly increased the ability of biological species to succeed in life and to speciate further.Why Classification Is ImportantIn order to describe and understand life’s diversity, we need a system of classification. People intuitively group all insects together and all birds together. All people have common names for collective groups of similar species: birds, snakes, insects, pines, orchids, and so forth. Some collective groups, such as beetles, are contained within larger groups, such as insects. Biologists organize these collective groups into a classification, an arrangement of larger groups that are subdivided into smaller groups, each reflecting their degree of evolutionary relatedness. Classifications help us to catalog and describe life’s diversity, which is the first step on the road to understanding this great diversity.Any collective group of similar organisms, such as insects or orchids, is called a taxon, and taxonomy is the study of how these taxa (plural of taxon) are recognized and how classifications are made. In a biological classification, species are grouped into successively more inclusive groups, or ‘higher taxa’: related species are grouped into genera (singular, genus), related genera into families, related families into orders, related orders into classes, related classes into phyla, and related phyla into kingdoms, such as the animal or plant kingdoms. All these are arranged as groups within groups, with the less inclusive (smaller) groups sharing more characters and the more inclusive (larger) groups sharing fewer characters. Thus, species within a genus have more characters in common than do families within an order.For example, human beings constitute the species Homo sapiens. Figure 6.1 shows, beginning on the right, that Homo sapiens is grouped together with Homo erectus and certain other fossil species into the genus Homo. (A genus always has a one-word name that is capitalized; a species has a two-word name in which the first word is the name of the genus; after the two-word name has been introduced, the genus may subsequently be abbreviated, for example, H. sapiens.) The genus Homo is grouped together with the extinct genera Australopithecus and a few others into the family Hominidae. This family is included in the orderPrimates, which also includes apes (Pondigae), monkeys (Cebidae and Cercopithecidae), and lemurs (Lemuridae). The primates are grouped together with rodents (Rodentia), carnivores (Carnivora), bats (Chiroptera), whales (Cetacea), and over two dozen other orders into the class Mammalia, including all warm-blooded animals with hair or fur that feed milk to their young. Mammals are one of several classes in the phylum Chordata, a group that includes all vertebrates (animals with backbones) and a few aquatic relatives such as the sea squirts and amphioxus. The Chordata and several dozen other phyla are together placed in the animal kingdom (Animalia). Animals are one of the several kingdoms to be discussed later in this chapter.“All those names”Communication among scientists requires a common vocabulary. Even hunters, gatherers, farmers, and other nonscientists need names for all the types of organisms familiar to them. However, in a linguistically diverse world, different people speak many different languages. Many years ago, the scientists of Europe discovered that they could best communicate with scientists in other countries by using Latin names. Thus, while the common names of animal and plant species differ from one language to another (e.g., dog, hund, cao, perro, chien), the scientific name, Canis, is the same for scientists the world over. Moreover, while modern languages change (modern English differs from Shakespeare’s and even more from Chaucer’s), scientific names are based mostly on Latin and Greek roots that do not change over time.The modern hierarchical form of classification, which we have just described, originated with the eighteenth-century Swedish naturalist Carl von Linné, who wrote under the name Linnaeus. Linnaeus also began a system in which each species has a two-word name, such as Homo sapiens. The use of two words for species names allows us to recognize millions of species with far fewer names. Thus, Canis familiaris isFigure 6.1The place of the species Homo sapiens in the classification of organisms. Reading from right to left shows the increasingly more inclusive taxa to which our species belongs. Reading from left to right focuses on taxa of increasingly narrow scope.KINGDOMSPHYLACLASSESORDERSFAMILIESGENERASPECIESKingdom ArchaeaKingdom EubacteriaKingdom ProtistaKingdom AnimaliaKingdom MycotaKingdom PlantaePhylum PoriferaPhylum CnidariaPhylum PlatyhelminthesPhylum EchinodermataPhylum ChordataPhylum MolluscaPhylum AnnelidaPhylum Arthropodamany other phylaClass AgnathaClass ChondrichthyesClass OsteichthyesClass MammaliaClass AvesClass ReptiliaClass Amphibiaseveral other classesOrder MonotremataOrder MarsupialiaOrder ChiropteraOrder PrimatesOrder RodentiaOrder CarnivoraOrder Artiodactylamany other ordersFamily CebidaeFamily LemuridaeFamily HominidaeFamily Pongidaeseveral other familiesGenusHomoGenusAustralopithecusa few more generaHomo sapiensHomo erectusHomo habilis the domestic dog, Canis lupus is the wolf, Canis latrans is the coyote, and Canis aureus is the jackal. Any person encountering any of these names for the first time immediately recognizes that they are all related species placed in the same genus. The name of each family is always based on the name of a well-known genus (e.g., Canidae for the dog family, comprising Canis and its relatives).Larger collective groupings, such as orders and classes, also have names. Most of these names are descriptive of some important characteristic of the group. Thus, the class Mammalia (from the Latin word mamma, meaning a breast) includes all species whose young are nourished with their mother’s milk, and the class Amphibia (from Greek roots amphi and bio, literally meaning ‘both lives’) contains frogs, salamanders, and other animals that live in water as gill-breathing larvae before they transform into lung-breathing adults. The names, in other words, have a meaning that relates to the organisms and that makes the name easier to learn and remember, at least when you only learn a few at a time. Unfortunately for many beginners, there are many names to know, and students who see them all at once may be overwhelmed by the sheer number of unfamiliar terms. We suggest that you begin by simply learning to recognize the same name on repeated encounters—it is, after all, just a name. If you learn the meaning of the name (which often means learning its Latin or Greek roots), it may help you to associate it with an important characteristic of the group. Remember that a classification is a tool designed to make communication easier.Taxonomic theoryIt is easy for students to look upon classifications as fixed and unchanging, but this is a false impression. Each classification is really just a hypothesis about how best to describe the variation among the organisms being discussed. If you read several accounts of the classification of the same group of organisms, you will probably find that not all authorities follow exactly the same classification. How, then, are classifications made? Sometimes, one person may become an expert on a particular group of organisms and then everyone accepts their classification as authoritative, but this situation is uncommon. More often there are multiple researchers, each following a slightly different classification, and each attempting to attract followers to their way of thinking. So how do scientists determine that one classification is preferable to another for the same group of organisms?One important goal of classification is to summarize and communicate what we know about groups of organisms (taxa). Thus, one criterion of a good classification is that it should aid in describing variation among taxa, summarizing both their differences and their similarities. Early classification systems were based on common physical structures, and members of each group were therefore expected to share visible characteristics. Many familiar groups recognized by ordinary people were given formal names and recognized in the classification, for example, birds— class Aves. Fishes, insects, clams, ferns, and orchids were also recognized in many early classifications; some of these groups are still recognized today. One reason that these taxa are useful is that there are many shared similarities that unite all their members and that distinguish these taxa from related taxa. However, other groupings, such as ‘worms,’ were shown to be heterogeneous when the included organisms were studied more closely; such unnatural groups are usually abandoned.Another goal of classification is to describe evolution. In order to describe all the different descendants of some ancient species, we clearly need some collective name for the group. Such a group is called a clade (from a Greek word, meaning branch), and the study of branching patterns in evolution, from common ancestors to their descendants, is therefore called cladistics. On a family tree such as the one shown in Box 6.1or in Figure 5.1, a clade consists of any branching point, representing an ancestor, and all the lines branching from it above, representing its descendants. In traditional practice, the taxa and their groupings were decided upon first, and family trees were then offered as explanatory hypotheses that justified the classification. Cladistics reverses this order, deriving the family tree first and then basing the classification on the tree.Biologists who follow cladistics develop family trees and classifications in which each larger taxon corresponds as closely as possible to a clade. After years of intensive study of a large and varied group of organisms, they make lists of important anatomical features and other characters that they think will help in classification. Such characters may include the occurrence of particular plant pigments; reproductive adaptations such as seeds or hard-shelled eggs; the presence of openings in the skull; the number and shape of teeth; the presence of certain glands and their secretions; or the anatomical structure of the limbs and other body parts. Often, characters present only in larvae or in embryonic life stages are used. After many such characters are listed for the species being studied, the biologist will deduce (sometimes with the aid of a computer program) the family tree that can explain the evolution of these characters with the smallest number of evolutionary changes. That is, if five species all possess a certain shared character, five changes would be required if each acquired the character independently, but only one change would be required if the character were acquired by an ancestor common to all five. From information of this kind, the five species are assigned to a clade, meaning a common branch of the family tree. This approach usually produces a consistent pattern, with smaller clades nested within larger clades. If, however, one character does not fit consistently with the others (that is, if it suggests clades that cannot be nested with the clades suggested by other characters), then that character tends to be discarded as misleading and the family tree is then based on the remaining characters. Once a family tree has been established, a classification is then drawn up, based on this family tree, by giving a name (e.g., Insecta or Diptera) and a rank (e.g. class or order) to each clade. As an example, Box 6.1 shows how a family tree and classification of land vertebrates may be derived.Molecular biology (including genomics) provides further evidence that can be used to construct classifications. First, the DNA sequences or protein sequences of various species are compared. Older molecular approaches simply compared all pairs of species for the overall similarity of their molecular sequences and grouped species into a classification based on the percentage of overall similarity (or percentage homology).BOX 6.1 Evolution and Classification of the Land VertebratesThe following example presents a simplified version of cladistics, the procedure commonly used to formulate a family tree and base a classification upon it. The organisms in this example are the land vertebrates, including amphibians (frogs, salamanders, etc.), turtles, lepidosaurs (lizards and snakes), crocodilians, birds, monotremes (egg-laying mammals such as the platypus), marsupials (pouched mammals), and placental mammals (those retaining the young inside the uterus throughout gestation). The groups (taxa) being classified are compared with an ‘outgroup’ of organisms outside the assemblage being classified, but related to it. Characters present in this ‘outgroup’ are presumed to be primitive (or ancestral) for the assemblage in question. In this example, lungfish are the outgroup.First, a character matrix is prepared as follows:TAXON CHARACTERS12345678910111213egg with amnion hairwarm blooded single centrale bone two-windowed skull shellopening in lower jawslit-shaped anus feathersmajor arteries connectedlive birthsuperficial jawopening muscleplacentanonoyesyesyesyesyesyesyesnonononononoyesyesyesnononononoyesyesyesyesnonoyesyesyesyesnonononononoyesyesyesnononononoyesnonononononononononoyesyesnonononononoyesnonononononononononoyesnononononononoyesnononononononoseldomnononoyesyesnonononononoyesnononononoseldomnonononoyes14pouchnononononononousuallynoIn this matrix, each taxon being classified is listed as either having or lacking each of the character traits used in the study. In our example, we are only using 14 characters; professional studies usually use many more than this.Our characters are as follows:An egg containing certain internal membranes (amnion, etc.), capable of being laid on landHair or furMaintenance of a constant, warm body temperature by using heat generated through physiological activity (endothermy, commonly called “warm blooded”)A single centrale bone in the ankleA skull with two window-like openings behind the eyeA shell enclosing most of the bodyA window-like opening in the lower jawA transverse, slit-shaped anus
plumage
An opening between the major arteries as they exit from the heart, permitting the blood to be diverted right or left as needed to balance pressure when the animal divesGiving birth to live youngA jaw-opening muscle belonging to a superficial layer encircling the neck, and used instead of a deeper muscle beneath the jawsA placenta formed by two embryonic membranes (chorion and allantois) and attaching to the inner wall of the uterus during gestationA pouch in which the young is nursed following its birthFor this matrix of characters, the family tree shown here is the simplest one possible, meaning that it requires the fewest evolutionary changes. Each labeled transition on the tree marks the evolution of a trait shared by all taxa on all of the branches to the right of that point. The family tree can be constructed from the character matrix by hand or by a computer program, using the following basic protocol:Allow all the taxa sharing a derived trait (a ‘yes’ in the above matrix) to form a single branch of the tree. Allow the various branches all to be nested in one another. For example, the land-based egg (character 1) is presumed to have evolved only once, in a common ancestor of all the animals possessing this trait, that is, all of the animals to the right of the branch labeled character 1. If all of the characters evolved only once, then the tree is finished.Where the first strategy does not result in a tree with each character showing up on only one branch of the proposed tree, we choose the simplest family tree as being the most likely. When a few characters do not fit in consistently it may indicate that the character trait evolved but then was lost by some, but not all, species in a group, or that the character evolved more than once (by convergence). When this happens, select the tree that requires the fewest evolutionary changes, minimizing the number of character traits for which we must assume multiple origins or acquisition and subsequent loss. In the family tree shown here, warm body temperature (3) is shown as having evolved independently in birds and in mammals. A different tree would result in many more traits for which multiple origins must be assumed.The tree formed by this protocol allows us to recognize the clades (branches of the family tree) that form the basis for the classification. Some of the taxonomic groupings supported by this particular family tree are shown as brackets on the right of the diagram. ‘Reptiles’ are in quotation marks because they are a group that does not correspond to a clade in this arrangement.Outgroup (lungfishes)AmphibiansTurtlesLizards & snakesCrocodiliansEgg-laying mammalsMarsupialsPlacental mammalsThe newer approaches use the methods of cladistics to construct family trees with the smallest number of evolutionary changes needed to explain the patterns of variation, as explained earlier.We have said that one goal of classification is describing groups with many physical characters in common, and that another goal is describing evolutionary history. Thankfully, these two goals usually result in very similar classifications. When they do not, more investigation is needed to determine the cause. If coherent groups, sharing many characters in common, do not correspond to clades, then an explanation is needed. Perhaps two unrelated groups evolved similar adaptations by convergence (see Chapter 5), developing many resemblances by analogy. Another possibility is parallel evolution, in which similar trends occurred independently several times among closely related groups. Perhaps some investigators were mistaken in describing or evaluating characters, for example, by misinterpreting one bone as a different bone, or by failing to recognize that a structure that appeared to be the same in two species had different embryological origins and was therefore a different structure in each case. One thing that is certain is that taxonomic disagreements often serve as a spur to further research when biologists attempt to discover the reasons behind the disagreement. After further research, classifications often change. For instance, the barnacles that grow on rocks or on ships were once thought to be related to clams or other filterfeeding animals with hard shells, but a study of their embryology revealed that they were built from the same parts as lobsters, shrimp, and other members of the class Crustacea, with which they are now classified.1 The class Mammalia includes whales and bats along with the more numerous terrestrial species (rodents, monkeys, cats, bears, deer, elephants, humans, and manyothers). Why is this grouping a useful one? Think of as many reasons as you can.THOUGHT QUESTIONS2 Think of a large group of organisms that you know something about. How would a biologist decide which of several possible classifications is best for this group? What would she or he look for? What kind of evidence is relevant? (These are among the most basic questions of taxonomy.)Modern Classifications Recognize a Great Difference Between Procaryotic and Eucaryotic CellsIn Chapter 1 we introduced the cell as the unit of organization for living things. A great gulf separates the major types of organisms on the basis of the structure of their cells. Bacteria and certain other organisms have a simple cellular structure with no internal compartments. In contrast, animals, plants, fungi, and protists have more complex cells with internal compartments and a true nucleus bounded by a membrane. Every modern classification of organisms gives prominence to this fundamental distinction of cell types.Procaryotic cellsThe first organisms to evolve were simple cells with no internal compartments and thus no nucleus. A membrane called the plasma membrane formed an outer boundary of the cell and kept its contents inside. Simple cells of this type are called procaryotic cells (Box 6.2). Procaryotic cells lack most of the complex internal structures possessed by more advanced (eucaryotic) cells. Procaryotic cells have a single chromosome, consisting of only nucleic acid without any protein. The DNA double helix of this chromosome is joined end to end in a circular form resembling a closed necklace. The region of the cell containing this procaryotic chromosome is not surrounded by a membrane or set apart from the rest of the cell in any other way. Many procaryotes also have fragments of DNA, called plasmids, which can detach from the chromosome, lead an independent existence for a long while, and then reincorporate into the chromosome (see Chapter 4, pp. 98–99 and Chapter 11, p. 400).Bacteria are procaryotic cells, and a majority of procaryotes are bacteria. Two other groups of organisms that are procaryotic cells are the blue-green photosynthetic organisms (Cyanobacteria) and the very primitive Archaea.Eucaryotic cellsPlants, animals, fungi, and protists are examples of organisms composed of eucaryotic cells (see Box 6.2). Eucaryotic cells have various internal parts, called organelles, which are bounded by intracellular membranes separating the various functions of the cell into different compartments. A defining characteristic of eucaryotic cells is the presence of a nucleus surrounded by a double membrane called the nuclear envelope (the name eucaryotic means ‘true nucleus’). The nucleus contains rod-shaped chromosomes composed of DNA and proteins. Many types of cell organelles are shown and explained in Box 6.2. Eucaryotic cells also have an internal network of protein filaments called a cytoskeleton. These filaments determine the shape of the cell and keep many organelles in their positions. Contraction of these filaments may help to move the whole cell. Keep in mind, however, that there are a vast number of variations on these cell types, both among species and among the various specialized cells within multicelled organisms; there is probably no actual cell that exactly matches the accompanying diagrams.Some eucaryotic organisms are single-celled (unicellular) and others are multicellular. All procaryotic organisms are unicellular.Endosymbiosis and the evolution of eucaryotesIn Chapter 5 we outlined some of the evidence for the origin of life under hydrogen-rich (reducing) conditions. Chemical fossils left by the earliest organisms provide evidence for the presence of chlorophyll (and thus photosynthesis) during the time when the atmosphere changed to its pre-sent oxygen-rich composition. Simple structural fossils of the earliest organisms, between 4.0 and 4.2 billion (4.0–4.2 ¥ 109) years old, show that they were single cells about the size of modern procaryotic cells, or roughly one-tenth the size of eucaryotic cells. Larger cells, comparable in size to modern eucaryotic cells, do not appear in the fossil record until about 1.5 billion years ago. But how did eucaryotic cells originate?From procaryotes to eucaryotes. According to a theory first championed by the American cell biologist Lynn Margulis in the 1970s, eucaryotic cells arose from procaryotic cells by a process called endosymbiosis (literally meaning ‘living together inside’). According to this theory, large procaryotic cells incapable of performing certain energy-producing chemical reactions (those of the Krebs cycle, described in Chapter 10, pp. 349–351) engulfed smaller procaryotic cells able to carry out these reactions. The larger (host) cells could obtain energy by digesting the smaller cells, but they could obtain even more energy if they allowed the smaller cells to go on living inside them and then used the products of the energy-producing reactions. In this situation, host cells that allowed the smaller cells to persist were favored by natural selection over host cells that digested the smaller cells. Over time, the smaller cells became energy-producing cellular organelles called mitochondria (Figure 6.2).Eucaryotic cells that are capable of photosynthesis have additional organelles called chloroplasts. The pigments that carry out photosynthesis are contained within these organelles. Chloroplasts are believed to have evolved by a process similar to that described above for mitochondria. In this case, however, the smallercells were cyanobacteria capable of photosynthesis. The larger cells achieved greater growth potential by harboring these smaller cells rather than digesting them. The large cells containing photosynthetic organelles did better and reproduced in greater numbers than similar cells without chloroplasts, and cells with these organelles ultimately persisted while many others without chloroplastsFigure 6.2The origin of eucaryotic cells according to the widely accepted theory of endosymbiosis.large, ancestral, procaryotic cell with one circular chromosomesmaller procaryotic cell with energy-producing capability (Krebs cycle enzymes) died out.In support of the theory of endosymbiosis is the fact that both chloroplasts and mitochondria have their own types of membranes and their own DNA, separate and different from those of the eucaryotic host cells that contain them, but similar to the membranes and DNA of procaryotic organisms. The presence of chloroplasts or other plastids is used in this book (and many others) as the defining attribute that determines the boundaries of the plant kingdom, which we discuss later.nucleus withrod-like chromosomes and nuclear envelopephotosynthetic procaryotic cell (becomes chloroplast)smaller cell, over time, became mitochondriaearly eucaryotic cellmitochondrion (each cell has many)capture of photosynthetic symbiont, which gives rise to chloroplastsBOX 6.2 Procaryotic and Eucaryotic Cells ComparedThe great differences between procaryotic (bacterial) cells and eucaryotic cells (including both animal and plant cells) are shown in the accompanying drawings and also in chart form. ribosomes single chromosomecell wallcytoplasmplasma membraneGolgi apparatusnuclear envelopenucleolusnucleuslysosomevesicleribosomeendoplasmic reticulumcytoplasmplasma membranemitochondrioncentriolecytoskeletal filamentsglycocalyxvesicleGolgi apparatusnuclear envelopenucleolusnucleusribosomelysosomecentral vacuolecytoskeletal filamentsendoplasmic reticulumplasma membrane cell wall starch plastidmitochondrionchloroplastplasmodesmastructurefunctionpresent in procaryotic cellspresent in eucaryotic cellsplant cellsanimal cellsplasma membraneprotection; communication; regulates passage of materialsDNAcontains genetic informationnuclear envelopesurrounds genetic materialseveral linear chromosomescontain genes that govern cell structure and activitycytoplasmgel-like interior of cellcytoskeletonaids in cell and organelle movement and in maintaining cell shapeendoplasmic reticulumtransport and processing of many proteinsGolgi apparatusadds sugar group to proteins and packages them into vesiclesribosomesprotein synthesis (translation) along mRNAlysosomescontain enzymes; aid in cell digestion; have a role in programmed cell deathmitochondriaprovide cellular energychloroplasts and other plastidscapture sunlight; produce energy for cellcentral vacuolemaintains cell shape; stores materials and waterflagella (whiplike appendages)cell movementsimple propeller typecomplex undulating typecomplex undulating typecilia (hairlike appendages)cell movement; present only in certain types of cellscell wallprotects cell; maintains cell shapeglycocalyxsurrounds and protects cellpili (hairlike appendages)mating; adherenceplasmodesmatacell-to-cell communicationEucaryotic diversity. As we have seen, evolutionary change occurs when natural selection acts on genetic diversity. Species evolve when new reproductive isolating mechanisms arise. Eucaryotic organisms such as animals and plants have speciated very often, so that most of the known species alive today are eucaryotic. In this section we examine the evolutionary advances that have taken place among eucaryotic organisms.Crucial to the success of eucaryotic organisms are a number of important evolutionary advances. Of these, sexual reproduction and multicellularity evolved early, and perhaps repeatedly, among organisms whose bodies were still small and simple. The vast majority of eucaryoticorganisms reproduce sexually, meaning that new individuals are formedonly after a process of genetic recombination (see Chapter 2). In most cases, this means that new individuals derive their genes from two parents. Sexual recombination may initially have evolved because it was a simple yet efficient way of generating new gene combinations. If an organism produces a thousand offspring by asexual reproduction, all of them will, in the absence of a mutation, be genetically identical to the parent. Even if a mutation occurs, the offspring will still be very similar to the parents. Sexual recombination changes this. If an organism produces a thousand offspring through sexual recombination, they will differ genetically from the parent and also amongst themselves. Given the uncertainties of future conditions, the chances of a few offspring having better (i.e. more highly adapted) gene combinations than the parent are greatly increased if reproduction is sexual. Also, among the many offspring, more than one favorable combination of genes may arise, and these may eventually result in different kinds of organisms (i.e. different species). Thus, in eucaryotic organisms, sexual recombination supplies a mechanism to generate increased diversity, and it is therefore not surprising that there are so many different species of eucaryotic, sexually reproducing organisms in the world today.Multicellularity probably evolved more than once independently. One route by which multicellularity evolved was by way of colonial organization. Single-celled organisms could in some cases maintain hospitable conditions better if they clumped together into small colonies. The aggregation into colonies would certainly reduce the surface area of each cell exposed to the outside environment because much of its surface would be in contact with its neighbors. The reduced surface area would aid in maintaining homeostasis. At first, all the cells in such a colony would be the same, and each would carry out all life processes, as before. As colonies grew larger, however, some interior cells began to lose contact with the outside environment altogether, and this began a simple division of labor between surface cells and interior cells. The interior cells were now in a more protected position, but they could no longer meet their own needs without having nutrients supplied to them or wastes taken away by other cells. The surface cells had to help supply nutrients to the interior cells and remove their wastes. In addition, certain functions (such as feeding or defense) could in most cases be carried out more efficiently by surface cells, while other functions (such as reproduction) could often be carried out better by the interior cells. Over time, the functions of cells in different parts of the organism became increasingly different from one another, and complexity thus increased in most cases.1 Of what type of cells are the following organisms composed? Draw a typical cell for each organism, and name its major distinguishing principle.THOUGHT QUESTIONSBacillus anthracis, the bacterium responsible for causing anthrax in humans
Elephant
Venus Flytrap Six kingdoms of organisms are included in three domains The largest taxa of all are traditionally called kingdoms. The animal and plant kingdoms have been recognized for centuries, and the earliest classifications of organisms recognized only these two kingdoms. Plants have long been distinguished as immobile organisms with rigid cell walls that can use sunlight as a source of energy. Rather, the animals were recognized for their ability to move, their lack of cell walls, and their inability to harvest energy directly from sunlight. This two-kingdom classification continued to be used despite the discovery of animals that do not move and other organisms, such as bacteria or fungi, that do not fit into the plant or animal kingdoms. Advances in our knowledge made possible by electron microscopy, particularly the discovery of the profound structural differences between prokaryotic and eukaryotic cells, have led to important changes in classification. In 1963, a Five Kingdoms classification system was first proposed and widely used. Organisms have not changed, but our disposition of them has, because classifications are socially constructed, that is, they are devised by humans and accepted as a matter of social convention. To say that a classification scheme is socially constructed does not mean that the process of creating a classification scheme is arbitrary or that all schemes are equally valid. Classifications are now generally understood as hypotheses about how organisms are related through ancestral patterns. As more and more knowledge about organisms accumulates, this knowledge is used to test hypotheses and replace discarded hypotheses with new ones. The division of living things into five kingdoms was simply a widely accepted theory, not immutable facts. In fact, most biologists are now adding a recently discovered but evolutionarily ancient sixth kingdom, Archaebacteria or Archaea. Archaea, bacteria, and cyanobacteria are the only prokaryotic organisms. We use the Six Kingdoms classification in this book. Even more recent direct comparisons of DNA sequences have shown that archaea and eubacteria differ greatly from each other, even more so than eubacteria differ from various eukaryotes. Figure 6.3 A family tree based on comparison of DNA (or RNA) sequences showing the arrangement of organisms into three domains. including bacteria and cyanobacteria) and a third for all organisms with eukaryotic cells - the eukarya (Figure 6.3). presumably related (see also Figure 6.3). We now examine ARCHAEAMarine Gp 1Zea CryptomonasEUCARYA all six kingdoms, which differ from one another in the details of cell structure, development, nutrition, and general morphology. A classification of organisms appears on our website (under Resources: Classification), and students should refer to it repeatedly as they read the rest of the chapter. Domain and Kingdom Archaea The domain Archaea contains a single kingdom called Archaea or Archaebacteria. The Archaea are one of the two prokaryotic kingdoms and are characterized by the fact that they can only live in very special environments. Some members of the Archaea, the methane producers, live in anoxic environments, such as B. in the intestines of cows, where they undergo chemical reactions during energy consumption that produce methane gas (CH4) as a by-product. Others live in extreme environments once thought incompatible with life, such as areas of high salt concentrations, the edges of thermal vents in the ocean floor, or in hot springs. Scientists reasoned that adaptation for such extreme environments must require very different enzymes from those previously known, which proved to be so. One enzyme that can operate on DNA at very high temperatures is now used in the polymerase chain reaction, central to much work in biotechnology (see Chapter 3, p. 81).Domain and kingdom EubacteriaThe domain Eubacteria, like the Archaea, contains but a single kingdom. This second procaryotic kingdom, now called Eubacteria, includes the more commonly known bacteria and the blue-green cyanobacteria. There is a great deal of diversity among bacteria. There are a handful of cell shapes: spherical, rodlike, gently curved (bananalike), and even spiral (like a corkscrew) (Figure 6.4). There are also differences in the structure of the cell wall, as revealed by commonly used staining techniques such as the Gram stain. An even greater diversity exists at the biochemical level. Some bacteria can tolerate oxygen in their environment and others cannot. Some bacteria can metabolize certain sugars and others cannot; the cyanobacteria can use cellular pigments to synthesize sugarsFigure 6.4Bacterial diversity:in shape; (B) in structure of cell walls.(A) individual cocci:string of cocci:cluster of cocci:rod-shaped:spirochete:MicrococcusStreptococcusStaphylococcusEscherichia Treponema lipopolysaccharide layerlipid monolayerouter membrane peptidoglycancell membrane (lipid bilayer)Gram-positive cell wall Gram-negative cell wallBOX 6.3 The Six Kingdoms of OrganismsPLANTAEANIMALIAMYCOTAGnetophytaGinkgophyta AnnelidaMolluscaCycadophytaAnthophytaNematodaArthropodaBasidiomycotaAscomycotaConiferophytaChordataNemertinaLycophyta Sphenophyta Pteridophyta PsilophytaRhodophytaHepaticae Anthocerotae MusciHemichordataEchinodermataPlatyhelminthesCtenophoraZygomycota DeuteromycotaPhaeophytaChlorophytaPoriferaCnidariaOomycotaChytridiomycota MyxomycotaEuglenophytaPROTISTAChrysophytaSporozoaCiliophora SarcodinaARCHAEAMethanobacteriaPyrrophytaMastigophoraMyxobacteria ActinomycetesCyanobacteria ChloroxybacteriaRod-shaped bacteria SpirochaeteEUBACTERIAThe placement of certain organisms differs among experts. In particular, the algae are sometimes included with plants, sometimes with protists, and sometimes divided between these two kingdoms. For further details, see the classification on this book’s Web site, under Resources: Classification.A small group of organisms, some of them adapted to extremely hot environments and many producing methane as a product of metabolism. Nucleic acid sequences of these organisms show them to be only distantly related to Eubacteria, with which they share the procaryotic type of cell structure shown in Box 6.2.The vast majority of procaryotic organisms, including the typical bacteria and Cyanobacteria (bluegreen bacteria). No well-defined nucleus or nuclear envelope, nor any type of organelle (such as mitochondria or endoplasmic reticulum) that requires internal membranes.Eucaryotic unicells without plastids or cell walls. Various adaptations for locomotion may be present (cilia in one group, whiplike flagella in another group, protoplasmic extensions called ‘pseudopods’ in the largest group), but one group lacks motility and resembles the fungi in reproducing by spores.Some authorities list the algae here rather than among the plants. This and the remaining three kingdoms all have eucaryotic cells, as explained in Box 6.2.Eucaryotic organisms with plastids, including various algae, mosses, liverworts, ferns and fern allies, conifers and a vast array of flowering plants from buttercups to orchids and from grasses to trees.Most plants have nonmotile life stages and cells surrounded by cell walls, whose presence strengthens plant tissues. Nearly all possess chlorophyll a and are capable of carrying out photosynthesis using sunlight.Nonphotosynthetic eucaryotic organisms with cell walls and absorptive nutrition, reproducing by means of spores. Includes slime molds, yeasts, mushrooms, and various other forms.Eucaryotic organisms without plastids, usually possessing a life stage with at least some locomotor capabilities, and developing by means of an embryonic stage consisting of a hollow ball of cells (blastula). No chlorophyll or photosynthesis; no cell walls. with the aid of sunlight (a process called photosynthesis), while most bacteria cannot. Some bacteria can move with the use of a simple flagellum, while others cannot. Many bacteria are free-living (in soil, for example), but many other species live only in a narrow range of host species. For example, most bacteria that use dogs as hosts cannot live in humans. Molecular genetics is now providing new information, revealing that species diversity is immense within both the Eubacteria and the Archaea.Although only 4500 procaryotic species have thus far been characterized and described, it is now estimated that millions exist.We often think of bacteria as the ‘germs’ that cause disease, as many of them do. However, a far greater number of bacterial species are beneficial to humans, to other organisms, or to entire ecosystems. For example, bacteria decompose dead material into chemical forms that other organisms can then use to sustain life. Without such decomposition by bacteria, all other forms of life would soon cease. Certain bacteria (and a few cyanobacteria) are also important in the reactions of the nitrogen cycle (see Chapter 11, pp. 374–375), which also sustains nearly all other species on Earth. Biotechnology uses bacterial plasmids and bacterial enzymes, and many industrial processes, including the making of cheese, yogurt, and sauerkraut, depend on chemical reactions performed by bacteria. We will discuss bacterial diversity further in Chapter 17.All members of the Eubacteria, whether bacteria or cyanobacteria, are single-celled organisms, but they often grow in colonies or filaments of many individual cells attached to a substrate or to one another. Some of these colonies have characteristics that differ from characteristics of single cells of the same species; they thus exhibit what may have been the first step in the evolution of multicellularity.Domain EucaryaAll the remaining kingdoms have eucaryotic cells and are therefore placed in the domain Eucarya. The earliest eucaryotes, known as protists, remained small and in most cases unicellular. Multicellularity evolved independently several times and forms the basis for the division of the Eucarya into Protista and three additional kingdoms. An absorptive type of nutrition evolved in one group of eucaryotes, the fungi (kingdom Mycota). Although some fungi remained single-celled, most are now multicellular and carry out their absorptive nutrition with the aid of thin, absorptive filaments. Chloroplasts evolved in another group of eucaryotic organisms, and these organisms became plants (kingdom Plantae). Protective structures for the egg cells evolved among later plants, as did vascular tissue, seeds, and flowers. In yet another large group of eucaryotes, motility became increasingly developed, and multicellular animals (kingdom Animalia) evolved from this group. Many important innovations evolved later on among animals, including bilateral symmetry, body cavities, segmented body plans, and, in our own phylum, backbones.Kingdom ProtistaThe earliest eucaryotes were simple, single-celled organisms. These species and their immediate descendants, those lacking the characteristics of the plant, animal, or fungal kingdoms, are placed in the kingdomProtista (Figure 6.5). Among protists, mechanisms evolved to ensure that, when cells divided, all their chromosomes would be present in the offspring cells. Mitosis and meiosis (see Chapter 2) first evolved among the Protista, as did sexual recombination. By having haploid gametes that joined during fertilization to produce diploid fertilized eggs (zygotes), the eucaryotes became able to generate new genetic combinations, thus producing great genetic variation in every generation. Because variation is the raw material on which natural selection works, sexual recombination increased the rate of evolution among eucaryotes.Eucaryotic organisms initially evolved in aquatic habitats; only much later did several eucaryotic groups independently colonize the land. Among the early eucaryotes, there must have been a great selective advantage in being able to move from place to place to find food or to escape from unfavorable conditions. Several different mechanisms for motility (movement) evolved, and the major kinds of protists are distinguished by these adaptations. The earliest protists had contractile protein filaments that allowed the cells to change shape and creep through their surroundings. One large group of protists, the phylum Sarcodina (containing Amoeba and its relatives), change their body shape to create movement. These protists move by sending out extensions called pseudopods; the flow of cytoplasm into the pseudopod determines the direction of movement. Another large group of protists, the phylum Mastigophora (or Flagellata), achieve motion through a whiplike structure (called a flagellum). A third group of protists move by means of numerous hairlike structures (called cilia). Representatives of these three groups of protists are shown in Figure 6.5. A fourth group of protists are nonmotile; this group, the Sporozoa, includes the parasites that cause malaria (see Chapter 7, pp. 226–227).Kingdom PlantaeOne of the great achievements of the early eucaryotic organisms was the acquisition of chloroplasts, which allowed these organisms to increase their energy production by photosynthesis. The simplest organisms possessing chloroplasts are called algae; all of them lack specialized tissues. Some experts place the single-celled algae among the kingdom Protista, and others place all the algae there, but many more experts include all algae in the plant kingdom, as we do in this book. The Plantae can thenFigure 6.5Representatives from several phyla of the kingdom Protista.Amoeba (phylum Sarcodina) Trypanosoma (phylum Mastigophora) Paramecium (phylum Ciliata)cilianucleus0.05 mmFigure 6.6Representative algae belonging to several phyla of the kingdom Plantae. Their different photosynthetic pigments are responsible for many different colors.be defined as eucaryotic organisms possessing chloroplasts, chlorophyll pigments, and a cell wall that commonly contains cellulose. (A few plant species have lost the pigments, but they still have all the other hallmarks of plants.)Different groups of algae are distinguished by the types of photosynthetic pigments that they contain, by the chemicals that they use to store energy, and by various other adaptations. Representative algae of different groups are shown in Figure 6.6. One group of microscopic algae, called dinoflagellates, can occasionally exhibit sudden growth into huge oceanic blooms called ‘red tide.’ These algae produce a toxin that accumulates in shellfish that eat the algae, and this toxin can cause illness— even death—in people who eat contaminated shellfish.The algae are ancient, aquatic plants, and they provide clues to the beginnings of multicellularity within the plant kingdom. Within several groups of algae, independently of one another, multicellular aggregations evolved. At first, these aggregations were just colonies of similar cells, similar to those formed by the green alga Volvox (see Figure 6.6). Then colonies began to function as multicellular single organisms. Cells located in different places within evolving organisms began to develop differently. Evolved differences between surface cells and those in theinterior, or between cells near the top and the bottom of a former colony, allowed the organisms to take advantage of the differences in environment between the various locations.Another group of ancient plants, the simple yet multicellular Bryophyta (mosses, liverworts, and hornworts), are important because they provide clues for the move from aquatic to terrestrial environments. The bryophytes have aDulse (Palmaria), a red alga (phylum Rhodophyta)Ascophyllum, a brown alga (phylum Phaeophyta)layer of sterile, nonreproductive cells that surround and protect their egg cells; this adaptation permitted these plants to emerge from aquatic environments and colonize the land, although they still live in relatively moist environments. Most botanists believe that bryophytes evolved from green algae because important photosynthetic pigments and other characteristics are shared by both groups. Three speciesVolvox, a microscopic green alga (phylum Chlorophyta)Peridinium, a one-celled dinoflagellateof bryophytes are shown in Figure 6.7.Bryophytes do not have deep underground parts because all parts of the plant carry out photosynthesis and therefore need to be in the light. They cannot grow very tall because they lack vascular tissue that would conduct fluids and because they lack the roots and stems that would provide anchorage and support. They are therefore nonvascular plants.Vascular plants with specialized tissues. Land plants were small at first and were restricted to moist habitats (such as the bryophytes discussed above), but some plants evolved vascular tissues, which allowed them to grow much taller, and these became the vascular plants (Tracheophyta). The most familiar and ecologically dominant plants are all vascular plants, and they include the largest and most conspicuous organisms in most terrestrial habitats. Vascular plants come in all shapes and sizes—a sample of this diversity is shown in Figure 6.8.In algae and other simple plants, each cell carries out its own photosynthesis, absorbs its own nutrients, and gets rid of its own waste products. The increasing specialization of cells in vascular plants allows different parts of each plant to perform different functions efficiently. Groups of similar cells are organized into tissues, and groups of tissues are organized into organs such as leaves and roots. For example, each leaf is an organ, while each cell layer within a leaf is a tissue. The simplest plants containing separate types of tissues are the Bryophyta, but the diversity and complexity of tissue types increases dramatically among vascular plants. Photosynthesis is carried out principally in the leaves, and other plant parts are also specialized for particular functions. Roots are specialized for water absorption and fruits for reproduction and dispersal. The division of labor among different parts of the plant would not be possible without the specialization of plant tissues, particularly the vascular (conducting) tissues that efficiently transport materials from one part of the plant to another.We will examine vascular plants further in Chapter 11.Specializations of flowering plants. The most highly evolved vascular plants reproduce with the aid of seeds, which contain small diploid embryos capable of being dispersed to new locations away from the parent plant. These plants have branching roots and leaves with multiple veins. The largest and most diverse, as well as ecologically dominant, group of seed-producing plants is that of the flowering plants (Angiospermae orConocephalum, a thalloid liverwort Marchantia, another thalloid liverwortFigure 6.8An assortment of vascular plants (Tracheophyta), belonging to several groups.Nephrolepis, a fern (phylum Pterophyta), showingAnthophyta). The seeds of flowering plants develop within elaborate reproductive structures called flowers (see Figure 6.7). Eggs, each with a haploid set of chromosomes, are produced by the female part of the flower within the ovary. The male part of the flower produces haploid gametes (sperm) within pollen grains in the anthers. Pollination is the introduction of the pollen onto the stigma, the female receptive surface of the flower (Figure 6.9). A pollen tube grows from the pollen grain to the ovary, where the sperm fertilizes the egg, resulting in a diploid zygote. Many flowers are pollinated by wind, but a much larger number are pollinated by insects. The relations between flowering plants and the insects that pollinate them are often quite elaborate and are crucial to much of the diversity and also the evolutionary success of both flowering plants and insects (see Chapter 18, p. 645 and pp. 664–665).After fertilization, the zygote undergoes cell division and becomes anembryo, and the structures surrounding the zygote mature into a seed. The seed-bearing structures in a flower ripen into fruits, defined as ripened ovaries that contain seeds. In addition to the seeds themselves, fruits often contain tissues that attract various animals by means of conspicuous col-ors, special odors, carbohydrate nutrients, or a combination of these. Animals that eat the fruits may disperse the seeds in their feces, often far from the parent plant. Seeds are also dispersed in other ways (Figure 6.10). Among the fruits that humans eat are many that we commonly recognize as fruits (e.g., apples, peaches, melons) and others that we do not always regard as fruits reproductive structures on the underside of the leafEquisetum, a horsetail (phylum Arthrophyta)Pinus, the white pine (phylum Coniferophyta)(e.g., nuts, grains, cucum-bers, tomatoes, peppers, eggplant).Flowering plants or angiosperms (phylum Anthophyta)Kingdom MycotaOrganisms of the kingdom Mycota are commonly known as fungi. These organisms typically live on dead or decaying organic matter that they absorb through threadlike extensions called hyphae. Fungi have mitochondria, but not chloroplasts, andDaisy(Chrysanthemum)Trillium (Trillium)Rose (Rosa)so they do not carry out photosynthesis.Typical fungi (subkingdom Eumycota) have cell walls and are nonmotile, but a few primitive fungi (subkingdom Myxomycota) have motile stages in their life cycles. For example, the slime molds such as Dictyostelium (Figure 6.11) have multicellular reproductive stages that look like fungi and carry out absorptive nutrition, but at other times they live as motile, amoebalike individual cells. Thus, they are thought to resemble an early stage in the evolution of multicellularity. Yeasts, morels, and certain molds belong to the phylum Ascomycota, which includes both single-celled and hyphal growth forms. Most ascomycetes can reproduce either sexually or asexually. Mushrooms belong to the phylum Basidiomycota. Their feeding structure consists of a branched network of fine hyphae; the familiar mushrooms (composed of tightly packed hyphae) are their reproductive structures. All fungi reproduce with the aid of spores, which are minute haploid gametes that are not distinguishable as eggs or sperm. Fungi useful to humans include edible mushrooms, yeasts (used in brewing, baking, and biological research), and the mold Penicillium, the source of the antibiotic penicillin. Several types of fungi are shown in Figure 6.12.Kingdom AnimaliaAnimals are multicellular organisms with eucaryotic cells and an embryonic life stage consisting of a hollow ball of cells called a blastula. Most animals have at least some motility during some stage of their life cycle.As we have seen, there are many highly successful forms of life that are not animals. Even within the animal kingdom, most animals are very different from the group to which we belong. In fact, the majority of animals lack a stiffening backbone and are called invertebrates. The animal kingdom also includes a great diversity of life strategies, and each is biologically successful within the habitat that it occupies.The animal kingdom is divided into about 30 phyla. Experts differ on the exact number of phyla because they are not in agreement about how to classify some animals. Some small phyla are not included in the following survey, but they are listed in the detailed classification found on this book’s Web site, under Resources: Classification.Minimal organization and the sponges. Multicellular organization in animals takes several forms. The simplest animals are sponges (phylumpollenFigure 6.9Diagram of a complete flower, containing both male and female parts together.After fertilization and ripening, the ovary becomes a fruit. Variations in the number and structure of the parts shown here are among the most useful characters in plant classification. Some plants have incomplete flowers in which there are separate male flowers with undeveloped female parts and female flowers with undeveloped male parts. anther (produces pollen)filamentpetalgrain pollentubestigma style ovaryovule (within ovary)egg cell (within ovule) sepalFigure 6.10The dispersal of seeds in different kinds of fruits.Porifera) (Figure 6.13). Various cell types are present in these aquatic animals, including wandering amoebalike cells, barrel-shaped cells with hollow interiors, and cells with a whiplike flagellum surrounded by a ‘collar.’ These cells, however, are not organized into different tissue layers,When food is available, free-living single cells move about and divide.Figure 6.11Life cycle of the slime mold Dictyostelium (kingdom Mycota, subkingdom Myxomycota).spore0.01 mm6 Each spore may germinate and give rise to a newmotile amoebalike cell.2 As environmental conditions become unfavorable, aggregates of identical cells form. spores5 Specialized cells forma fruiting body and spores.3 Cell aggregates form a creeping slug stage.4 The cells of the slug startto specialize their functions.as they are in all other animal phyla. Sponges have a variety of adaptations to deter predators that would otherwise feed upon them: all sponges have sharp, needlelike structures (spicules), and many sponges also secrete poisonous chemicals. The sponges that lacked these defenses disappeared long ago.Tissue layers and the phylum Cnidaria. The simplest animals having cells organized into tissues are found in the phylum Cnidaria (Figure 6.13). Like the sponges, these are aquatic animals. In the Cnidaria and in the embryos of all other animals except sponges, one portion of the hollow blastula puckers inward and turns inside-out. The resultant cupshaped structure, called a gastrula, contains two distinct layers of cells: the layer that has moved to the inside is called endoderm, and the layer that remains on the outside is called ectoderm. These structures are shown in Figure 6.14.The ectoderm and endoderm form two distinct tissue types, the beginnings of the differentiation of multicellular animals into a variety of such tissues. As in plants, tissues are groups of similar cells that formsheets or other integrated structures, each specialized to perform a dif-ferent function. We discuss tissues further in Chapter 12. In addition to the ectoderm and endoderm, the gastrula contains an endoderm-lined central cavity, open to the outside. The fact that all animals (exceptFigure 6.12Some types of fungi (kingdom Mycota, subkingdom Eumycota).A morel, Morchella (phylum Ascomycota)sponges) go through such a gastrula stage in their development is strong evidence that they all share a common ancestry.The two tissue layers are arranged in two basic body plans among the Cnidaria. One plan (called a polyp) has the central cavity opening upward. Cnidaria with this body plan usually grow attached to the ocean bottom or to other animals; many live in large colonies that we recognize as corals. The other body plan (called a medusa) has the central cavity opening downward. Cnidaria with this body plan float freely in the water, and most can contract portions of their body to control their movement. Because of the large amount of jellylike material that lies between the outer and inner layer of cells, most of these Cnidaria are popularly known as ‘jellyfish.’ The major subgroups of Cnidaria are distinguished on the basis of whether their life cycle includes only one of these body plans or both of them. Both cnidarian body plans have a series of tentacles surrounding the opening of their central cavity. These tentacles contain specialized stinging cells, which are used to defend the animal against predators.Bilateral symmetry and the flatworms. Most sponges, and a few other types of animals that live attached to the ocean bottom, have irregular body shapes that show no symmetry. Other sponges, and all members of the Cnidaria, have a radially symmetrical body plan, that is, a body plan arranged in a circle. (If you look down on them from above, you will see the same anatomical details repeated over and over around the edge of this circle.) Regardless of body plan, a cnidarian has the same chance of finding something nutritious, or something dangerous, in any direction, and natural selection has therefore favored radial body plans among these animals.The vast majority of animals, belonging to over two dozen phyla in the animal kingdom, are characterized by bilateral symmetry, meaning that their bodies can be divided by a central plane such that structures on the left side of this plane are mirror images of corresponding structures on the right side. Bilateral symmetry is believed to have evolved in animals as an adaptation that came along with forward movement. Imagine an animal that creeps along the ocean bottom in such a way that one end of its body is in a forward position. Movement would be made easier by a streamlined or elongated body. New discoveries, whether ofThe black bread mold, Rhizopus (phylum Zygomycota)A mushroom, the poison Amanita (phylum Basidiomycota) food or of danger, would be more likely to be made with the front end. Under these conditions, natural selection would favor the development of a front end with sense organs (eyes, feelers, taste organs, sound and motion detectors), feeding organs, and possibly also aggressive weapons.An animal that creeps along the ocean bottom may also be expected to react differently to the water above than to the sediment below, and so natural selection would tend to favor organisms having structures on the top (dorsal) surface that differ from those on the underside (ventral). However, any structure or ability that is adaptive on the right side is equally adaptive on the left, and organisms would have no selective advantage if their right side differed from their left. As a result of selection under these conditions, body plans that are bilaterally symmetrical are common in the animal kingdom and present in many different phyla.The simplest animals with bilateral symmetry are the flatworms of the phylum Platyhelminthes (Figure 6.15). They have somewhat elongated bodies, with sense organs concentrated at one end, which is recognizable as a head. The body is flattened, with broad upper and lower surfaces that in many species differ from one another in coloration and in other ways. The body plan is bilaterally symmetrical, with right and left halves of the body being mirror images of one another. Flatworms have a middle layer of tissue (called mesoderm) in addition to the ectoderm and endoderm (see Figure 6.14). All the animals yet to be described in this chapter have tissues derived from these three basic layers.Assembly-line digestion and the roundworms. One way in which flatworms are similar to cnidarians is in their digestive system, which is just a sac with a single opening that serves as both entrance and exit. With this arrangement, much of what is discarded as waste is immediately taken in again as food, making the system very inefficient. A further inefficiency is that every region of the digestive tract, and every group of cells in the digestive lining, must be capable of performing the entire digestive process from beginning to end. With this arrangement, cells cannot specialize to carry out early or late steps of digestion.Phylum CnidariaHydra, a polyp Jellyfish or medusaFigure 6.14Early stages in the embryology of animals. Adult sponges develop directly from a modified blastula stage. All other animals go through both blastula and gastrula stages. Members of the phylum Cnidaria form adult stages that still resemble gastrulas, whereas most other animals develop a middle layer (mesoderm) that gives rise to additional internal organs.A more efficient arrangement, which first evolved in roundworms (phylum Nematoda) and several related phyla (Figure 6.15), is an assembly-line digestive tract with an entrance, the mouth, at the front end and an exit, the anus, at the hind end. With this arrangement, selection canzygoteblastula adultsponge ectoderm endoderm gastrulaadult cnidarian opening that becomes themouth in protostomes or the tail end in deuterostomesmesodermendoderm no body cavitye.g. flatwormmesodermpseudocoel (body cavity)e.g. roundwormectoderm mesodermcoelom (body cavity)e.g. annelid and humansfavor organisms in which the cells near the front end can perform the early stages of digestion more efficiently and those near the hind end are more efficient in completing the later stages. Certain parts of the digestive tract can now specialize in the processing of different types of nutrients, or of hard substances requiring mechanical break-up (see Chapter 10). Waste products are now discharged more efficiently because they are released from the hind end and left behind as the animal moves forward.The evolution of body cavities. In the course of creeping forward along the ocean floor, some animals occasionally found reason to burrow into the bottom sediment. Burrowing is usually accomplished by a mechanical process of wedging the front of the body farther forward, then forcefully inflating part of the body to make it wider, then repeating the process. Forceful widening of the body thus alternates with forceful elongation, both in time and space. At any moment when the narrow portions of the body are pushing forward, the other parts of the body are widening to give the parts in front of them something against which to push.This alternation of widening and elongating can be done much more efficiently if the body contains one or more fluid-filled cavities. Because fluids like water are not compressible, squeezing a fluid-filled bag (like a water balloon) in one place or in one direction causes it to bulge elsewhere. Thus, any fluid-filled cavity can be forcefully widened by contracting muscles running front to back, while the same cavity can be forcefully elongated by contracting muscles that encircle its girth.In the course of evolution, various types of fluid-filled cavities of different constructions and different embryological derivations evolved in different phyla. These phyla are classified in part according to the nature of the body cavity and the cells lining its interior. Roundworms, horsehair worms, rotifers (see Figure 6.15), and a handful of other animal phyla are characterized by body cavities lined with cells derived from several embryonic layers, including endoderm. The remaining phyla described below all have body cavities entirely lined with mesoderm; such a body cavity is technically called a coelom (see Figure 6.14).Figure 6.15An assortment of invertebrate animals belonging to various phyla. Of the animals shown here, the flatworm (phylum Platyhelminthes) has no body cavity, while the roundworms (phylum Nematoda) and rotifers (phylum Rotifera) have a body cavity whose lining is made from several different embryonic tissue layers.Giant flatworm (phylum Platyhelminthes)Rotifers (phylum Rotifera)Roundworm (Trichinella ) cyst in muscle tissue (phylum Nematoda)Figure 6.16Protostome animals with a true coelom.Protostome phyla and the evolution of segmentation. The remaining animal phyla all have mesoderm-lined body cavities. They are separated into two large groups, the protostomes and deuterostomes, which evolved in different directions. The protostomes include the mollusks, annelids, arthropods, and several smaller groups (Figure 6.16). All of them share certain embryological similarities, such as the way in which their body cavity develops and the derivation of the mouth.At some point in protostome evolution, the mesoderm and its body cavity became subdivided into a series of individual blocks or pouches (somites). These blocks of tissue were arranged from front to rear, setting the stage for the evolution of segmentation of the body. Some of these animals, such as the annelid worms, are thoroughly segmented in both larval and adult stages, but others, including many mollusks, have lost most of their segmentation as adults.Animals of the phylum Annelida, of which the earthworm is a familiar example, are anatomically arranged as a series of repeated segments; all the body segments are similar to one another in size and in anatomical structure. Segmentation permits parts of the body to work as selfcontained units, allowing rhythmic swimming or crawling motions. The worms crawl through soil or sediment by using rhythmic waves of muscle contraction squeezing against the fluid-filled body cavity of each segment. A few body segments elongate while the next few widen. Waves of elongation alternate with waves of widening of the body segments, and these alternating waves pass down the length of the body from the front end to the rear. The annelid worms have no legs, but they do have tiny bristles (called setae) that stick out of their sides and anchor the widened, nonmoving segments of the body to the surroundings, giving the elongated segments something to push against as they move forward.The phylum Arthropoda is the largest and most diverse phylum of the entire animal kingdom. The Arthropoda include lobsters, crabs, shrimp (see Figure 6.16), barnacles, spiders, scorpions, centipedes, millipedes, and insects. Insects alone account for over two-thirds of theTree snail (phylum Mollusca) Shrimp (phylum Arthropoda)Copepod (phylum Arthropoda) A water bear (phylum Tardigrada) Tropical earthworm (phylum Annelida) animal kingdom and over half of all living species on Earth. Arthropods evolved from annelid ancestors. The body segments of arthropods are fewer than in annelids, and these segments are more specialized, differing from one another in both size and anatomy. Most notably, the arthropods have a series of leglike structures that differ in most cases from segment to segment. Arthropods have a strong, protective outer coating (called an exoskeleton), making each segment rigid. The rigid segments are separated by flexible hinge regions. The legs are also arranged as a series of rigid segments separated by flexible, hinged joints, giving the phylum its name (from the Greek, arthro meaning ‘hinged’ or ‘jointed,’ plus pod meaning ‘leg’ or ‘foot’).Animals of the phylum Mollusca are in most cases protected by a hard outer shell, secreted by a special layer called the mantle. Part of the mantle is retracted at the rear of the animal to form a mantle cavity that contains both an anus and gills that allow respiration in water. Anyone who has admired seashells has some idea of the tremendous variety of species of mollusks. In addition to the familiar snails, clams, and oysters, mollusks also include cephalopods such as the squid and octopus, inwhich the shell is hidden inside or has been lost entirely (see Figure 5.7,p. 135). The creeping movements of snails and the digging movements of clams are both very similar to the waves of contraction used by annelids.Evolution of the deuterostome phyla. The remaining phyla of the animal kingdom are deuterostomes. All deuterostomes have body cavities completely lined with mesoderm, but they have evolved separately from the protostomes described above. One major difference is in the manner in which the body cavity usually develops; another difference lies in the embryologic formation of the mouth. In protostomes, the gastrula opens to the outside by an opening that becomes the future mouth. That same opening in deuterostomes ends up near the hind end of the animal, just above the anus, while the mouth develops as a secondary structure at the other end. (Protostome means ‘first mouth,’ while deuterostome means ‘secondary mouth’.) Thus, in a very real sense, your head corresponds to an insect’s hind end (they are homologous), and an insect’s head corresponds to your rear.The deuterostomes and protostomes evolved separately, but some convergent adaptations have appeared. For example, a form of segmentation of the muscles and certain other body systems evolved independently in both groups.The deuterostomes include four phyla, all evolved from bilaterally symmetrical ancestors. All animals in these four phyla go through early (larval) stages of development that are bilaterally symmetrical, but a few become irregular (asymmetric) or radially symmetrical as adults. Two phyla, the echinoderms and chordates, are large groups.The phylum Echinodermata includes sea stars (starfish), brittle stars (Figure 6.17), sea urchins, sand dollars, crinoids (sea lilies, Figure 6.17), and sea cucumbers. The living species of echinoderms show a fivefold (pentameral) symmetry as adults, but their larvae are bilaterally symmetrical. Their other characteristics include a bumpy or spiny skin protected by calcium carbonate deposits and a water-vascular system through which sea water circulates in a series of tubes.Humans and other animals with backbones belong to the phylum Chordata (Figure 6.18). Also included in this phylum are several smallFigure 6.17Echinoderms (deuterostomes of the phylum Echinodermata).and unfamiliar sea creatures such as the sea squirts (also called tunicates) and the small sea lancet or amphioxus. The common ancestors of echinoderms and chordates probably lived attached to the ocean bottom, either directly or by means of a stalk. Many extinct groups of echinoderms grew this way (crinoids still do; see Figure 6.17), but most living echinoderms and chordates have a free-living, unattached way of life. The transition from attached to free-living is best shown by the tunicates in the phylum Chordata (see Figure 6.18). These small animals generally spend their adult lives attached to a rocky bottom. Here they sit and pump water through a large basketlike structure (the pharynx) whose numerous slits strain the water through while suspended food particles collect on a sticky, ciliated surface coated with mucus. The attached, filter-feeding existence of adult tunicates was the ancestral way of life for deuterostomes. Larval tunicates, by contrast, are actively free-swimming animals that resemble tadpoles. They swim by means of a long tail that sweeps back and forth like the tail of a fish, and the muscle blocks and nerves of this tail are segmentally organized. Free-swimming members of the phylum Chordata, including all fishes, have more in common with the tunicate ‘tadpole’ than with the filter-feeding adult.Although humans are obviously different from tunicates in many ways, as members of the Chordata they share major characteristics not found in any other group of organisms. Characteristics shared by all chordates include (1) a body axis containing a stiff, flexible rod (called a notochord), (2) a hollow nerve cord along the back, and (3) a series of openings called gill slits, located behind the mouth region. These three characteristics originate early in the embryo and are not retained in the adults of all species. For example, fish keep their gill slits throughout life and use them to breathe, but humans lose their gill slits long before birth, keeping only a few remnants here and there, such as the tube that connects the throat to the middle ear (see Figure 13.12, p. 480).Animals with backbones (Vertebrata). Among the members of the phylum Chordata, the majority are backboned animals that make up the subphylum Vertebrata. The stiff, flexible rod found in other chordates isCrinoid or sea lily Brittle starsfunctionally replaced in adult vertebrates by a backbone made of a series of individual bones or cartilages. Included in the vertebrates are four classes of fishes: (1) the jawless fishes; (2) the extinct, armored Placodermi; (3) the fishes with cartilage skeletons (including the sharks and rays); and (4) the fishes with skeletons of true bone (the group to which most fishes belong). There are more living species of bony fishesFigure 6.18Representatives of the phylum Chordata, another deuterostome phylum. All of these animals have embryonic notochords and gill slits. water in water outpharynx with gill slitsTree frog (class Amphibia)anus stomach Drawing of a tunicate (class Urochordata)Queen angle fish (class Osteichthyes) Coral snake (class Reptilia)Penguins (class Aves) Kodiak brown bear (class Mammalia) than of all the other vertebrate classes combined. All fishes are aquatic vertebrates that use gills to breathe and that swim by waving their hind end from side to side.The four remaining vertebrate classes evolved, directly or indirectly, from the bony fishes, and thus all have bony skeletons. First of these are the amphibians (class Amphibia), which include the frogs, toads, and salamanders. These animals lay eggs in water, and the eggs develop into aquatic, gill-breathing larvae, commonly called tadpoles. After a while, the tadpoles undergo a rapid developmental change (metamorphosis) into adults that have legs and in most cases lungs. Fossil amphibians are known from the Devonian period to the present day.Derived from the amphibians are the reptiles (class Reptilia), which include turtles, snakes, lizards, crocodiles, and many extinct species including dinosaurs. Unlike the amphibians, the reptiles have dry, scaly skin, and they lay their eggs on dry land (except for a few species that retain the egg inside the mother and give birth to live young). Fossil reptiles are known from the Pennsylvanian period to the present, but the Mesozoic era was populated by so many reptiles that it is often called theAge of Reptiles (see Figure 5.8, p. 137).One group of reptiles, the Archosauria, included the dinosaurs and other dominant reptiles of the Mesozoic era. Derived from this group of reptiles are the birds (class Aves), distinguished by their possession of feathers. Most bird adaptations have to do with flying, including adaptations (such as hollow bones and the loss of one ovary) that lighten the body, and the high metabolism (and thus the high internal body temperature) that flying requires. Feathers do double duty as a flight surface and as insulation.Another group of ancient reptiles had mammal-like features, and the class Mammalia, to which we belong, evolved from them. Mammals maintain a high and fairly constant body temperature, made possible by an insulating layer of hair or fur, supplemented in some cases by fat or blubber. A four-chambered mammalian heart prevents oxygen-rich blood from the lungs from mixing with oxygen-poor blood returning from other parts of the body. Also characteristic of mammals is the fact that they supply their young with milk, a secretion of the female’s mammary glands. Mammals include kangaroos, shrews, monkeys, humans, bats, rats, squirrels, rabbits, whales, dogs, cats, bears, seals, elephants, horses, pigs, sheep, cattle, and many other species.Humans are mammals because we share such mammalian characteristics as hair, a four-chambered heart, and the feeding of milk to our young. We are also chordates because we share in the embryonic gill slits and other characteristics that unite us with tunicates, amphibians, and other Chordata. We also share with all deuterostomes (chordates and echinoderms) the way our mouths develop embryologically. We share with many more phyla the anatomical structure and embryonic derivation of our body cavity, and with all animals the presence of motile cells and development from a blastula. We share the eucaryotic type of cell with four of the six kingdoms of organisms, putting us in the eucaryotic domain. The evolution of species over billions of years accounts for these patterns of shared characteristics.Why are algae sometimes considered protists? Why are they sometimes considered plants? How would you decide which is the better approach? If chloroplasts evolved only once, how would this affect your answer? What if chloroplasts evolved many times, independently?Find four or more books on botany or general biology. List the phyla or divisionsTHOUGHT QUESTIONSof the plant kingdom that each book recognizes. What similarities do you find? What differences do you find? How do you account for the differences?Many bilaterally symmetrical animals have a long, thin ‘wormlike’ body shape. What advantages do you think such a body shape can confer? What problems do you think can arise from such a body shape?Humans Are Products of EvolutionAs we saw in the last section, humans are one species among many. At what point in evolutionary history did our ancestors evolve into something we could call ‘human’? Answers to this question are reconstructed from fossils. The fossils help us to reconstruct our family tree, although there are frequent disagreements among scientists as to where a particular new fossil fits in.Our primate heritageAlong with monkeys, apes, and lemurs, humans belong to the mammalian order Primates (Figure 6.19). We share many characteristics with other primates, but we did not evolve from any present-day species. Most adaptations shared by primates are related to the requirements of life in trees. Most primates live in trees today, and those that do not had ancestors that did. Nonprimate mammals whose ancestors never lived in trees do not share these adaptations. Primate characteristics directly related to the requirements of locomotion in trees are: (1) the independent and individual mobility of the fingers, (2) the ability of the thumb to oppose the action of the other fingers, and (3) the presence of friction ridges on the palm of the hand and the sole of the foot. Primates have also retained some primitive characteristics that many other mammals have lost in the course of their evolution, including the five-fingered hand, the collarbone (clavicle), and the ability to rotate the two bones of the forearm. Unlike those mammals that rely heavily on the sense of smell, primates rely heavily on vision. Primates have vision that merges images from both eyes to give three-dimensional information (binocular vision). This binocular vision is possible because the eyes came forward to the front of the skull during early primate evolution, so that the visual fields from the two eyes overlap. The portions of the brain related to vision are expanded in primates, especially when compared to those mammals whose eyes are to the sides of their heads and whose right and left visual fields are largely separate. Also, the outer surface of the brain (the cerebral cortex; see Chapter 13) is more complex. The increased complexity of the primate brain is associated with an increased complexity of learned behavior (see Chapter 8). The reliance on learned behavior would be impossible without a lengthy period of very intensive parental care. Primates typically give birth to one offspring at a time. Primate nipples are restricted to a single pair in the chest region (other mammals have many pairs). Other mammals have two uteri, but in primates these are fused into a single uterus. Primates include lemurs, lorises, galagos, tarsiers, monkeys, apes, and humans. Among these, humans are most closely related to apes, but differ from all nonhuman primates in habitually walking upright.Early hominidsIn 1925, a fossilized child’s skull was discovered in a cave near Taung, South Africa, and was named Australopithecus africanus. Although theskull had both apelike and human features, most experts treated it as just another ape. Additional fossils of A. africanus were discovered subsequently (Figure 6.20). These fossils included skulls with a very low opening for the emergence of theSlow loris (Nycticebus coucang)Squirrel monkey (Saimiri sciureus)Chimpanzee (Pan troglodytes)spinal cord from the base of the brain, showing that the skull balanced on top of an erect vertebral column. Parts of the foot, the pelvis, and the lower part of the vertebral column were also present, and these structures confirm that Australopithecus walked upright and was therefore more like humans than like apes. Direct evidence for upright walking comes from the discovery of a set of footprints at Laetoli, Tanzania, approximately 4.5 million years old. Primates that walk upright are placed in the family Hominidae and referred to as hominids.Scientists have since unearthed the remains of several other species of Australopithecus and related early hominids. The relationships among these hominids are shown in Figure 6.21. The oldest species is the recently discovered Sahelanthropus tchadensis, approximately 7 million years old. This earliest hominid had a very small brain and certain apelike dental features. Another early hominid, Australopithecus anamensis, lived about 4 million years ago in Kenya. A. anamensis is thought to be the ancestor of all later species of Australopithecus and a close relative of the small hominid Ardipithecus ramidus. Another species, Australopithecus afarensis, about 3.5 million years old, is represented by the wellknown skeleton known as Lucy, a female about 1.3 meters (slightly over 4 feet) in height. Enough of Lucy’s skull is preserved to permit us to estimate the size of her brain in proportion to her body size, and these proportions are consistent with the hypotheses that A. afarensis was the common ancestor of the genus Homo and of several later species of Australopithecus. Two of these later species, A. robustus and A. boisei, were considerably larger than the better-known Australopithecus africanus, which lived from approximately 3.0 to 2.0 million years ago.Two other early hominids are Orrorin tugensis, an early species esti-mated to be about 6 million years old, and Kenyanthropus platyops, a flatfaced species about 3 million years old. In both cases, the dates are uncertain and in dispute. Few fossils of either species are known, and these fossils are fragmentary. For these reasons, the exact relationship of either of these two species to the better-known hominids is unclear.Of the species we have described, Sahelanthropus tchadensis, Australopithecus anamensis, and Australopithecus afarensis were probably along the line leading to Homo; the various other species were probably side branches of the family tree that died out without leaving any surviving descendants. The earliest Australopithecus came well before the earliest known Homo (about 4 million years ago, or half a million years after the Laetolil footprints), but later species of Australopithecus persisted side by side with Homo, at least in East Africa.The genusModern humans (Homo sapiens) and at least two extinct species are placed in the genus Homo (Figure 6.22). The oldest species of Homo was Homo habilis, which lived inEast Africa from about 3.5 to1.7 million years ago, coexisting with Australopithecus boisei and perhaps with other Australopithecus species. H. habilis had a brain that was small in absolute terms (about 400 cm3, compared with 1200–1500 cm3 for most modern humans), but the proportions of the brain to body size were more compa-Figure 6.20Fossils of the genusAustralopithecus. rable to those of Homo than to those of Australopithecus.Adult Australopithecus africanus(Sterkfontein, South Africa)Side view of Australopithecus africanus(Sterkfontein, South Africa)Figure 6.21A family tree of the family Hominidae. Dark orange areas show the known time range of species represented by fossils. Some dates are approximate.millions of years ago0246H. habilis has been found contemporaneously with certain types of tools, including simple stone tools. It is generally presumed that H. habilis was the maker of these tools.A later species, Homo erectus (see Figure 6.22), is now known from fossils from about 1.5 million to 300,000 years old in China, Java, Europe, and several parts of Africa. A cave site at Choukoudian, China (near Beijing), has heat-fractured stones indicative of the use of fire. There is also evidence of round or oval tents supported by poles and held down along the margins by a circle of stones.H. erectus was the ancestor of Homo sapiens, the species to which living humans belong. As H. sapiens evolved, tools became more sophisticated, and were in many cases mounted on wooden shafts. The H. sapiens that lived in Europe from about 150,000 to 50,000 years ago are called Neanderthals. Neanderthals hunted deer, horses, and even rhinoceroses and mammoths. Healed surgical wounds show that theseskilled hunters took care of sick companions, set broken bones, and even performed simple brain surgery. They buried their dead and decorated the graves with flowers of preferred colors, mostly white or cream-colored. The decoration of graves is thought by several anthropologists to indicate a belief in an afterlife.The more modern H. sapiens that replaced the Neanderthals were Upper Paleolithic people (including the Cro-Magnons) who lived from about 50,000 to 15,000 years ago. They had an even greater variety of tools, including fishhooks and harpoons. They hunted wooly mammoths and large herd animals. They also left records of their activities in the form of cave paintings, showing their interest in hunting and their understanding of both animal anatomy and physiology. By prominently drawing the heart and singling it out as a target, these hunters showed that they understood how vital thisorgan was. Their drawings of* = species recognized by some authorities and not otherspregnant deer and of mating rituals show that they knewenough reproductive biology to understand the relationships between mating, birth, and subsequent herd sizes.The discovery of agriculture ushered in a new phase of human history called the Neolithic. With the planting and harvesting of crops, humans began to settle down into villages, which later grew into towns and cities. Civilization has greatly changed the ways in which we live our lives. The rapid pace and power of cultural change leaves many people wondering whether biological evolution of H. sapiens has become a thing of the past. If we need to travel faster, the argument goes, our species tames horses or builds automobiles instead of evolving longer legs for faster running. Evolution by natural selection is much slower than cultural innovation. In this view, the future development of our species resides more in our technology than in our bodies.No one questions that cultural changes in human beings have far outstripped biological ones as the most rapid and far-reaching changes taking place today. Cultural innovation spreads rapidly, in part because there are no species barriers to prevent transmission from one human group to another. (Language barriers and geographic barriers can always be crossed, especially in the age of television and jet travel.) The ease of travel and the global spread of people and their culture has brought us to an era in which there is no significant geographic isolation of human populations. Without geographic barriers, no reproductive isolating mechanisms will evolve, and all humans will remain one species. Cultural change is also more rapid than biological evolution because new inventions and other culturally acquired characteristics are inherited, although not genetically. Each generation inherits the stored knowledge of past generations (in libraries and museums, for example), along with tools (from tractors to telephones to satellites) and the technology needed to design and build new and better tools in the future.Figure 6.22Fossils of the genus Homo.Homo erectus (Koobi Fora, Kenya) Homo sapiens (Quafzeh, Israel)Although natural selection continues to take place, the environment, and therefore the traits favored by selection, have changed because of our own culture. Many of the selection forces that shaped human evolution in the past, including famines, epidemics, and predators, have been greatly diminished in modern times. Many traits that were once disadvantageous have become much less so. For example, poor eyesight is no longer an important barrier to survival and reproduction in societies that supply eyeglasses.Human evolution has not stopped, however, because there continue to be situations in which the chance of survival or reproduction differs among people as a consequence of their genotypes. In our own species, genetic conditions such as cystic fibrosis, Tay–Sachs disease, muscular dystrophy, and others continue to cause numerous deaths before reproductive age, despite the best that medical technology has to offer. Other diseases that are generally survivable may reduce reproductive capacity, which decreases fitness. For example, chondrodystrophy is a rare disease, controlled by a dominant gene, in which the cartilage tissue turns bony at an early age, resulting in a form of dwarfism. Most chondrodystrophic dwarfs enjoy fairly normal health as adults, but have only about one-fifth as many children as their nondwarf siblings. Lowered reproductive rates are also found in diabetics. As these examples show, natural selection continues to affect the human species. Biological evolution thus continues to operate and to interact with cultural evolution in all human populations.THOUGHT QUESTIONSThe Neanderthals were similar to us in many respects, though their skulls had a somewhat more ‘rugged’ appearance, with brow ridges and cheek bones protruding. How should we decide whether Neanderthals should be placed in their own species, separate from Homo sapiens?In Europe, Upper Paleolithic culture replaced the culture of the earlier Neanderthal populations rather suddenly.Do you think that the replacement of one set of tools and traditions by another took place mostly by conquest, by intermarriage, or by some combination of the two? What evidence would you look for to test one hypothesis against the others?Is the study of evolution static or changing? Find some recent news articles dealing with new fossil discoveries or other new findings that deal with evolution.Concluding RemarksThe classification of organisms into species and higher taxa is an important way to summarize many of the results of evolution. Classifications cannot be static because our understanding of evolution keeps improving. Biological evolution continues to act today in humans as it does in other species, although it now interacts with cultural evolution andSummary to Chapter 6 201technological revolution. Natural selection continues to operate by both differential mortality and differential reproduction, and continued selection will result in biological changes within all species, including humans. One frequent result of evolution within species is geographic variation. In the next chapter we examine some of the reasons for geographic variation within the human species.Chapter SummaryScientists make classifications that group species together into taxa on the basis of their similarities and their evolutionary history.The theory behind classifications is called taxonomy. One important school of taxonomy, called cladistics, bases classifications on the sequence of branching points in family trees and on making taxa correspond to clades.Early cells were procaryotic and contained no internal membranebounded compartments or internal structural fibers. Procaryotic cells have no nucleus and only a single chromosome, containing DNA but no proteins.Eucaryotic cells contain a variety of internal organelles (including a membrane-bounded nucleus), internal structural fibers, and multiple chromosomes containing proteins as well as DNA.Highlights of early eucaryotic evolution include the origin of organelles, the acquisition of chloroplasts and mitochondria by endosymbiosis, the evolution of multicellularity, and the origin of sexual recombination of gametes.Sexual reproduction, which involves genetic recombination, has greatly increased the possibilities for generating new diversity among eucaryotic organisms.Most procaryotic and some eucaryotic organisms practice asexual reproduction in which no genetic recombination takes place.Evolutionary highlights within the plant kingdom include the origin of protective layers around egg cells and the origin of tissues including vascular tissues. Vascular plants have tissues that conduct water and allow plants to have different organs devoted to different functions in different parts of the plant. Vascular tissues also allow plants to grow tall. Seeds and fruits have permitted flowering plants to adapt to many habitats not previously available to simpler plants.Highlights of animal evolution include the origin of bilateral symmetry, the evolution of body cavities, the development of segmented body plans, and the evolution of the backbone.Early human fossils are placed in the genus Australopithecus and several related genera. The genus Homo includes various fossils and all living people.CONNECTIONS TO OTHER CHAPTERSChapter 2 Differences in DNA structure help us to understand the relationships shown in our classifications.Chapter 4 Different species carry different genomes, and these differences can be used in classification.Chapter 5 Classifications reflect evolutionary history because differences among taxa are the results of branching evolution.Chapter 7 Geographic variation within the human species was formerly understood as a classification based on ‘races.’ It is now understood to be based on the same evolutionary processes that operate within all species.Chapter 8 Social behavior and reproductive strategies often vary among taxa and can be used in classification.Chapter 10 Differences in metabolic pathways can be used in classification, especially among bacteria.Chapter 11 Plant characteristics include the presence of chloroplasts responsible for photosynthesis. Plant classifications highlight the differences among plants, such as different photosynthetic pigments and the development of vascular tissues.Chapter 12 The same developmental pathways that lead to tissue differentiation can also lead to cancer.Chapter 13 Differences in brain anatomy among different species provide good evidence of evolution that can be used in classifications.Chapter 14 The presence or absence of drug molecules in plants can be useful characteristics in their classification.Chapter 16 Species close to us phylogenetically are susceptible to viruses similar to HIV.Chapter 17 Newly emerging infections can reflect the evolutionary origin of new strains of pathogens.Chapter 18 Biodiversity can best be understood by developing a comprehensive classification of all living species.PRACTICE QUESTIONSWhat are the major aims of classifications?Name the six kingdoms of organisms currently recognized.Name five organelles that eucaryotic cells possess but procaryotic cells do not.Name three or four evolutionary advances among plants that you consider most important in their classification. Why was each important?Why are arthropods, mollusks, and segmented worms grouped together? What do they have in common? What important differences characterize each of these phyla?What selection pressures fostered the development of each of the following characteristics?radial symmetrybilateral symmetrycomplete ‘assembly line’ digestive tractbody cavities
segmentation
Why are vertebrates grouped together with echinoderms? What evidence exists for this arrangement?What is the major anatomical difference between humans and apes? What is the major anatomical difference between the genus Australopithecus and the later members of the genus Homo?Examine Box 6.1, and identify three taxa that correspond to clades.IssuesHow can we describe and compare variation within and between populations?How is the study of population geneticsrelated to human variation?Why do human populations differ biologically?Do human races exist?Is there a biological basis for the idea of race? Is biology the most accurate descriptor of race?Will changing biological concepts of race diminish racism? Why or why not?Populations and population ecologyPopulation genetics (genetic variation,Hardy–Weinberg equilibrium, blood groups, genetic drift)Patterns of evolution (adaptation, physiology)Forces of evolutionary change (natural selection, environmental factors, communicable diseases, parasitism, human health)Gene action (molecular structure, genetic polymorphism)Scaling (body size and shape)Chapter OutlineThere Is Biological Variation Both Within and Between Human PopulationsContinuous and discontinuous variation within populationsVariation between populations Concepts of raceThe study of human variationPopulation Genetics Can Help Us to Understand Human VariationHuman blood groups and geography Isolated populations and genetic driftReconstructing the history of human populationsMalaria and Other Diseases Are Agents of Natural SelectionMalariaSickle-cell anemia and resistance to malariaOther genetic traits that protect against malariaPopulation genetics of malaria resistance Other diseases as selective factorsNatural Selection by Physical Factors Causes More Population VariationHuman variation in physiology and physiqueNatural selection, skin color, and disease resistance7203204Human Variationhe human species is highly variable in every biological trait. Humans vary in their physiology, body proportions, skin color, and bodychemicals. Many of these features influence susceptibility to disease and other forces of natural selection. Continued selection over time has produced adaptations of local populations to the environments in which they live. Much of human biological variation is geographic; that is, there are differences between population groups from different geographical areas. For example, northern European peoples differ in certain ways from those from eastern Africa, and those from Japan differ in some ways from those from the mountains of Peru. Between these populations, however, lie many other populations that fill in all degrees of variation between the populations we have named, and there is also a lot of variation within each of these groups.Central to the study of human variation is the concept of a biological population, as defined in Chapter 5 (p. 151), and as explained again later. Both physical features and genotypes vary from one person to another within populations, but there is also a good deal of variation between human populations from different geographic areas as the result of evolutionary processes. How do populations come to differ from one another? How do alleles spread through populations? How do environmental factors such as infectious diseases influence the spread? Why are certain features more common in Arctic populations and other features more common in tropical populations? Why do we think of some of these variations as ‘races’? These are some of the questions that are explored in this chapter.There Is Biological Variation Both Within and Between Human PopulationsAll genetic traits in humans and other species vary considerably from one individual to another. Some of this variation consists of different alleles at each gene locus; other variation results from the interaction of genotypes with the environment. The simplest type of variation governs traits such as those discussed in Chapter 3 (pp. 75–77), in which an enzyme may either be functional or nonfunctional. The inheritance of these traits follows the patterns described in Chapter 2, which you may want to review at this time. In particular, be sure that you understand the meaning of dominant and recessive alleles and of homozygous and heterozygous genotypes. Many other traits, as we saw in Chapter 3, have a more complex genetic basis. In this section we examine how biological variation is described.Continuous and discontinuous variation within populationsMany human traits vary over a range of values, with all intermediate values being possible; such variation is called continuous variation.Continuously variable traits, such as height, can often be measured in an individual and expressed as a numerical value. Other traits that vary continuously, such as hair curliness or skin color, are seldom expressed numerically, although theoretically they could be.Continuous variation can result from the cumulative effects of multiple genes, each of which by itself contributes a small effect. Dozens of known genes, perhaps even hundreds, influence height in one direction or another. If we make the simplifying assumption that these effects are independent of one another and that they add up, we can predict that a population of individuals will show a variation in height similar to the bell-shaped curve (normal distribution) of Figure 7.1. When we measure heights in any large population, we do in fact get a curve that closely matches this predicted curve. Many other continuous traits vary in much the same way as height. For most of these traits, a strong environmental component also exists. Height, for example, is strongly influenced by childhood nutrition as well as by genes. Environmental components of traits also contribute to the formation of a bell-shaped curve.A numerical description of continuous variation in a population requires the use of statistical concepts such as average (mean) values. The average values are characteristic of the population as a whole, not of any individual member within the group. For a particular group of people, we can calculate an average height, weight, or head breadth, but these averages are just statistical abstractions—there are perfectly normal individuals that differ from the average, perhaps even greatly, as can be seen in Figure 7.1. Thus, the group average for a continuously variable trait tells us little about any individual. Also, whereas height can actually be measured (and average height computed), concepts such as ‘tall’ are relative: a height that is average in England may be considered tall in India or the Philippines.Your individual traits result from both the genes that you inherited from your parents and the environmental factors to which you are exposed. What you inherit from your parents is a predisposition for a range of possible future variations in phenotype. For example, when a child is born, its exact height as an adult cannot be predicted, but if the mother and father are both significantly taller than average, it will, if it receives adequate nutrition, probably also be taller than average.Discontinuous variationFigure 7.1Continuous variation in a single population: all intermediate values are possible. within a population is represented by traits that are either present or absent, with no intermediate values possible. Most of these traits have a simple genetic basis, so that someone’s genotype may sometimes be deduced from their phenotypes and the phenotypes of their close relatives. Traits that vary discontinuously include blood groups and the presence or absence of conditions such as albinism or Tay–Sachs disease (see Chapter 3). A particularDistribution of height in a population whose average height is 165 cm (about 5’5”).140 150 160 170 180 190 cm5’0” 5’6” 6’0” phenotype for such a trait is either present or not in a particular individual and is generally not altered by environmental influences.To describe discontinuous variation in a population, we divide the number of people who have a particular phenotype by the total size of the population; the resulting fraction is the frequency of that phenotype. From these phenotypic frequencies, scientists can calculate the frequencies of the alleles responsible. These allele frequencies (originally called gene frequencies) are most easily studied for traits whose patterns of inheritance are known and simple. Like the average values of continuously variable traits, allele frequencies are characteristic of entire populations, not of individuals. All individuals have genotypes, but only populations can have allele frequencies.Variation between populationsThe study of genetic variation both within and between populations is called population genetics, and it includes the study of allele frequencies for discontinuous traits. The measuring of allele frequencies requires that the different genotypes, and the alleles responsible for them, can readily be distinguished from one another. It is for this reason that population geneticists often concentrate on those genes whose phenotypic effects are easy to tell apart. Most of those genes control discontinuously variable traits that are either present or not. Differences in the average values for traits that vary continuously are also of interest to population geneticists, but the study of these traits is more difficult because the phenotypes of continuously variable traits are often altered by environmental influences such as nutrition.One of the central tenets of modern biology is that evolution can occur only if populations are genetically varied. However, biologists did not always think in terms of evolving and variable populations. For over 2000 years, biologists believed that species were constant, unvarying entities. Plato and Aristotle had declared that each species was designed according to an ideal form that they called an eidos, often translated as ‘type’ or ‘archetype.’ Biologists following this view developed the morphological species concept. Each species was described as having certain fixed and invariant physical characteristics (morphology). The whole ‘type’ of that species was believed to be a cluster of ‘essential’ characteristics inherited as a single unit.Biologists now recognize that species are constantly evolving, largely as the result of natural selection working on the genetic variation that ispresent within populations (Chapter 5). The Human Genome Project (Chapter 4) has revealed that over 99.9% of the human genome is identical in all people. However, the remaining fraction of a percent varies geographically, meaning that populations from different locations differ from one another. We must have some clear way to describe this variation and to describe population groups.To define a population or a larger group of populations, we could sort people by some physical trait, such as distinguishing between people who are tall, short, or average in height. For any trait that we could choose, much of the variation exists within each and every population. If we chose some other physical trait, such as eye color or hair curliness, we would find that each physical characteristic results in a differentgrouping of the same people. In addition, we find that groupings based exclusively and strictly on any single trait always group together people who are quite dissimilar in many other respects (especially on a worldwide basis). For these reasons primarily, biologists prefer not to base the definition of population groups on physical characteristics.Instead of using physical characteristics to define populations, biologists use the term population to refer to all members of a species who live in a given area and therefore can interbreed with one another. Membership in a population is determined by geographical location and by mating behavior, not by physical characteristics. Populations that interbreed under natural conditions belong to the same species (Chapter 5). All humans are placed in a single species, Homo sapiens, because all of them have the capacity to mate with one another and produce fertile offspring. However, people in different geographical locations belong to different populations. Genetic variation within any population is usually less than in the species as a whole. In past centuries, geographic isolation kept many human populations more distinct than they are now with worldwide transportation and migration. Population boundaries are not the same as national boundaries. Several different populations may live in the same geographic area, especially if cultural factors have maintained their separateness and inhibited matings between them. Sometimes, these populations are distinguishable by their derivation from geographically separate earlier populations.Human populations in different places differ from one another in many physical traits. The average Canadian is taller than the average Southeast Asian, and the average African has darker skin than the average European. For natural selection, however, the characteristics that matter the most are those with the greatest impact on health and disease (or life and death). For example, cystic fibrosis and skin cancer are more frequent among people of European descent, but people of African descent have a higher risk of sickle-cell anemia and are more susceptible to frostbite if exposed to very cold temperatures. Most discontinuously variable traits that are examined closely show differences in allele frequency from one human population to another. For continuously variable traits, the differ-Figure 7.2Continuous variation in two populations with different mean values. ence between the averages oftwo populations is much less than the variation within either population (Figure 7.2). For example, the average height in the United States is taller than in China, but many Americans are shorter than the Chinese average and many Chinese are taller than the American average.Although it is easy to find human populations that differ from one another in both physical features (morphology) and genetic traits, it is usually very difficult to find sharp boundaryDistribution of height in two populations whose average values are 165 and 180 cmrespectively. The variation within each population is greater than the difference between the average values of the two populations. Note that one of these populations is identical to the one shown in Figure 7.1.140 150 160 170 180 190 cm5’0” 5’6” 6’0” lines dividing these populations from one another. If you were to walk from Asia to Europe and then to Africa, you would see populations differing only slightly, in most cases imperceptibly, from their neighbors, and you would meet representatives of the three largest population groups on Earth without finding any abrupt boundaries between them. Another way to say this is to say that variation between human populations is always continuous. This is so even when the trait in one individual is discontinuous. The population frequency of the allele responsible for the trait can vary continuously between zero (no one has the phenotype) and 100% (everyone has the phenotype). For discontinuous traits such as blood type, the allele frequencies of adjacent populations are generally close, just as is true for the average values of continuous traits, as seen in Figure 7.2.Concepts of raceHumans have developed various ways of describing both themselves and the other human populations with which they have had contact. Biologists (who study all forms of life) and anthropologists (social scientists who study human populations and human cultures) have assisted in these descriptions by studying and measuring certain physical traits and allele frequencies. There are many ways in which human variation can be described, and there are many uses to which these descriptions have been put. One of the most problematic has been the attempt to separate people into different races. As we will soon see, there are various different meanings to this term, all of them different from the term ‘population.’ The term ‘population’ always describes smaller and more cohesive units than the term ‘race.’ No physical features are used in defining populations, but some race concepts have been based on physical features. In this section we describe four different concepts of race in the order in which they originated. The older concepts have not entirely died out; they have in many cases persisted side by side with the concepts that came later.Races based on cultural characteristics. In the Bantu languages of Africa, the word for ‘people’ is bantu. Likewise, the Inuit word for ‘people’ is inuit. Every group of people has a name for itself and its members, and the name often means people or human. Names that people apply to other groups of people may simply be descriptive, but value judgments are often implied as well. In some instances, the value judgment implicit in the choice of name has been used to justify widespread abuses against the negatively labeled population. Such was the case when land and labor shortages resulted from large-scale cereal agriculture, a problem that arose independently in many places. A commonly developed solution to these shortages was to conquer neighboring people (the ‘other’) and confiscate their land. Slavery and several other systems of coercion were developed to secure the labor of conquered peoples. Slavery, oppression, and conquest all call upon the victorious people to practice certain atrocities on others that they would never tolerate within their own group. To justify these atrocities to themselves, and to protect their own members from practicing similar atrocities on one another, just about every conquering group has found it expedient to distinguish themselves from the ‘other,’ and furthermore to depict the conquered people as somehow inferior, subhuman, or deserving of their fate. Many of the groups that were culturally defined as races in the past are really language groups, cultural groups, or national groups that are hardly distinguishable on any biological basis from the group that traditionally oppressed them.The imposition of social inequalities between ‘Us’ and ‘Them’ is now recognized as racism. Racism has many meanings, but all of them include the belief that some groups of people are better than others, and that it is somehow justified or proper for the more powerful group to subdue and oppress the less powerful. In most cases, the motivation to conquer and oppress others came first; the racist ideology came later.The ‘races’ identified by the conquering group are socially constructed to serve the interests of the oppressors only. The distinctions and values of the oppressors are forcibly imposed on the oppressed, who are often taught to believe in their own inferiority. Most people now regard racism as unethical because it denies basic rights to many people and because it results in frequent crime, violence, and social conflict.Separation based on race serves better the political and economic causes that have engendered it if the distinctions recognized are declared to be ‘natural’ and unchangeable, as opposed to characteristics that can easily be changed by education or religious conversion. Scientists belonging to racist societies have therefore sometimes attempted to ‘prove’ that the traits characteristic of another race have an inherited basis that cannot easily be changed, an assertion called biological or genetic determinism (or hereditarianism). Behind such assertions is the view that a group identity (an ‘essence’ or Platonic eidos) can be inherited, a view for which there is no basis in genetics. Anthropologist Eugenia Shanklin documents several instances in which scientists conducted ‘scientific’ studies to help ‘prove’ the values and prejudices of their own social group. In their genocidal campaigns of the 1940s, the Nazis exterminated many millions of Jews, gypsies, Slavs, and other groups, but not until they had declared each of them to be an inferior ‘race.’Racism and hereditarianism are not synonymous, but they often gotogether as attitudes shared by many of the same people. The supporters of eugenics (see Chapter 3) had many followers, including Nazis in Germany and anti-immigrationists in the United States. These followers sought ways to prove the inferiority, and especially the biologically unchangeable inferiority, of other people.The other race concepts that we discuss later differ from this earliest concept, and resemble one another, in their avoidance of language, customs, and other cultural traits in the delineation of races. However, racism is not confined to those societies that embrace the cultural concept of race. Many biologists and anthropologists have pointed out that racism is also built into the the next concept, race delineated by body features.The morphological or typological race concept. Biologists who study plant and animal species often describe the geographical variation within a species by subdividing the larger species into smaller and more compact subgroups, each of which is less variable than the species as a whole. These subgroups are generally called subspecies, but within our own species they are called races. To bring the study of human variation more in conformity with that of other species, scientists began to restrict their attention to characters that could be studied biologically and to exclude personality traits, languages, religions, and customs more influenced by culture than by biology.Before the days of ocean-going vessels, most of the world’s people had only a limited awareness of human variation on a worldwide scale. Each population, of course, knew about other populations nearby, but in most cases adjacent populations differed only slightly from one another. When trade extended over great distances, it usually did so in stages, so that none of the traders ever had to go more than a few hundred miles from home. The trade routes were also in most cases traditional, meaning that traders and migrants had generally come and gone over the same routes for centuries. This contributed to a gene flow or mixing of alleles that lessened the degree of difference between populations that would be noticed along the trade routes.When explorers began to sail directly to other continents, they found people in other lands who differed more sharply from themselves in physical features. Many scientists subsequently became curious about the origin of these physical differences. Discussions of racial origins from about 1750 to 1940 tended to dwell on the origin of physical differences. A morphological definition of each race, based on physical features (morphology), was an outgrowth of the same thinking that had earlier resulted in a morphological species concept. At least initially, the major founders of this tradition were scientists who had no interest in oppressing the newly discovered peoples, so finding an excuse for racial oppression was less of a motive than was scientific curiosity. The emphasis was no longer on distinguishing only ‘Us’ from ‘Them,’ but on distinguishing among many different racial groups.By the 1700s, biologists were actively describing and categorizing the variation in all living species. The eighteenth century naturalist Linnaeus (Carl von Linné) divided the biological world into kingdoms, classes,orders, genera, and species (see Chapter 6). He also divided humans into four subspecies: white Europeans, yellow Asians, black Africans, and red (native) Americans. The use of physical features such as skin color and hair texture to define subspecies was common among biologists using a morphological race concept. Other scientists in this same tradition recognized more races or fewer, but each race was always described on the basis of morphological characteristics such as skin color, hair color, curly or straight hair, and the occurrence of epicanthic folds of skin over the eyes.Under the morphological concept of race, each race was defined by listing its common physical features as though they were invariant. For example, when describing a feature such as color, only one color was given, as if this color were invariant throughout the group and throughout time. This approach, which classified races on the basis of ‘typical’ or ‘ideal’ characteristics, ignoring variation, is called typology. Morphological definitions of race were always typological. Africans, for example, were declared to have black skins and curly hair, overlooking the fact that both skin color and hair form vary considerably from place to place within Africa and even within many African populations. All of the morphological characteristics were assumed to be inherited as a whole; a person was assumed to inherit a Platonic eidos (a ‘type’ or ‘essence’) for whiteness or redness, not just a white or red skin. Supporters of the typological concept of races were also supporters of a typological concept of species.Years after morphological races had been defined, closer scrutiny revealed both variation within the morphological races and intergradation between them across their common boundaries. A few Europeans tried to save the morphological definitions by proposing that each race had originally been ‘pure’ and invariant, and that present-day variation within any population was the result of mixture with other races. One zoologist, Johann Blumenbach (1752–1840), divided up humans into American, Ethiopian, Caucasian, Mongolian, and Malayan races. He thought that each of these races was originally homogeneous (that is, ‘pure’), and he named each after the place that he identified as its ancestral homeland. For example, white-skinned people are called ‘Caucasian’ because Blumenbach thought that this race originated in the Caucasus Mountains, east of the Black Sea.There is no scientific support nowadays for the concept of originally pure races or for the concept of different ancestral centers of origin of different races; human populations have never been homogeneous and have always been quite variable. In some cases, however, Europeans and others who feared for the ‘purity’ of their own group sought to pass laws limiting contacts, especially sexual contacts, between the races that they recognized. Most of these laws were brutal but still ineffective in stopping what were viewed as interracial matings. There is no scientific basis for the belief that such matings are in any way harmful. On the contrary, variation within any species confers a long-term evolutionary advantage because it provides the raw material that natural selection can use to adjust to changing environmental conditions.But hereditarian assumptions were even more strongly embedded in the morphological race concepts than they are in the culturally based race concepts. Lest one think that science has long since banished such attitudes in educated people, it is only necessary to point to the great storm of controversy that flourished over the subject of race and IQ in the 1970s. Arthur Jensen attempted to convince his readers that the mental abilities of African Americans were below those of other races and that these differences were fixed by heredity and unchangeable by educational means. A number of scientists, including Leon Kamin, Richard C. Lewontin, and Stephen Jay Gould, showed that his claims were unsupportable and based on fallacies and fabricated evidence. As recently as 1994, a book by Richard Herrnstein and Charles Murray once again brought up many of the same hereditarian arguments that had earlier been debunked (Box 7.1).One of the strange ironies of a racist past is that many attempts at remediation, such as affirmative action, continue to require, at least for a time, the identification and naming of the same groups that were used previously for racially divisive purposes. Attempts to ensure fair and nondiscriminatory treatment for members of different socially recognized racial groups (in housing, employment, schooling, and so forth) require that we first identify and study the groups that we wish to compare. In this way, societies trying to overcome a history of racism find themselves using the very racial classifications of their racist past in order to redress the injustices of past generations.Population genetics, clines, and race. Modern studies of human variation are based in large measure on genetics. Genetic variation betweenBOX 7.1 Is Intelligence Heritable?To address a question such as this, we must first define intelligence. Intelligence is not easily defined, but it includes the ability to reason and to learn new ideas and new forms of behavior, the measurement of which is far from simple. The biological bases for these abilities are likely to be multifaceted (Chapter 13), and genetic factors are likely to be the result of the interaction of many, many genes. Most discussions on the inheritance of human intelligence deal only with a single measure of this very complex trait, the IQ score, obtained from a test. IQ is not the same thing as intelligence and is at best an imperfect measure of mental abilities.Also, to address this question, we must define the word ‘heritable.’ Heritability is defined in statistical terms as the proportion of the population’s variation in some trait associated with genetic as opposed to environmental variation. Statistical association, or correlation, does not imply causation, and it certainly cannot be used to justify the claim that ‘there is a gene for’ the trait in question. One way to determine heritability of a trait in a domesticated species is to compare the variability of that trait in the population at large with the variability of the trait among highly inbred, genetically uniform individuals. Another way to determine heritability is to compare the variability that a trait exhibits at large with the variability of that trait among individuals raised in a standardized, experimentally controlled environment. Neither of these methods can be applied to humans, and the measures that are used to study humans are all indirect, complicated, and subject to criticism on technical grounds. For these reasons, there is no agreement on the heritability of any important human ability, including ‘intelligence.’ Moreover, because variation is a characteristic of populations and not of individuals, a term such as ‘60% heritable’ would simply be a ratio of variation in one population to variation in another and would not tell us anything about the genotype or phenotype of any individual.Numerous studies on IQ scores have shown the following:It is difficult to devise IQ tests that are free from cultural bias and from bias based on the language of the test, the gender and race of the test subjects, and the circumstances in which the test is administered.IQ scores seem to have both genetic and nongenetic components. Children’s IQ scorescorrelate strongly with those of their parents. The IQ scores of adopted children usually agree more closely with their adoptive parents than with their birth parents, although studies on adopted children have been criticized for a variety of reasons (see Chapter 3, pp. 71–72).IQ scores can be greatly improved by environmental enrichment. They can also be adversely affected by poor nutrition, poor prenatal conditions, and a number of other environmental circumstances.Populations historically subject to discrimination, such as African Americans in the United States, Maoris in New Zealand, and Buraku-Min in Japan, have average IQ scores about 15 points below those of the surrounding majority populations. However, these lower average scores do not always persist in people who migrate elsewhere: descendants ofBuraku-Min living in the United States have, on average, IQ scores on a par with those of other people of Japanese descent.In the United States, IQ scores of whites and also of blacks (African Americans) vary from state to state, in some cases more than the average 15-point difference between blacks and whites. Among African Americans born in the South but now living in the North, IQ scores vary in proportion to the number of years spent in northern school systems.Transracial adoption studies show that African American children adopted at birth and raised by white families had IQ scores close to (in fact, slightly higher than) the white average.Careful studies of matched samples in schools in Philadelphia failed to show significant average differences in IQ scores between black and white schoolchildren if differences in background were controlled. ‘Matched samples’ mean that children in the study were compared only with other children of comparable age, gender, family income level, parents’ occupation, and similar variables.Taken together, these data indicate that there is, at most, a small degree of heritability for IQ. They provide little support for the hereditarian claim that IQ is fixed and immutable, or that observed differences in scores cannot be diminished. They provide no support whatever for predicting any individual’s IQ score on the basis of their inclusion in any group. populations is continuous, and all boundaries between groups of populations are arbitrary. Even for traits that vary discontinuously and for which an allele frequency can be calculated for each population, geographic variation in allele frequencies is continuous between populations.A continuous increase or decrease in the average value, allele frequency or phenotypic frequency of any one trait is called a cline, after a Greek word meaning ‘slope’ (as in words like ‘incline’ or ‘recline’). Clines are an accurate (but lengthy) way of describing the geographic variation in each trait, one trait at a time, and each cline could be shown on a map. For a dozen characteristics, a dozen different maps would be needed, because the patterns of variation would in general not coincide.The maps in Figure 7.3 show the clinal variation in the allele frequencies of three blood group alleles. Before such maps of allele frequencies can be drawn, local populations must first be identified and sampled. For example, blood groups must first be studied in many local populations; then the allele frequencies found in each geographic area can be drawn on maps such as those in Figure 7.3. From maps such as these, we learn that large continental areas usually show gradual clines. Thus, Figure 7.3A shows a gradual south-to-north increase in the frequency of allele A across North America, and Figure 7.3B shows a gradual west-to-east increase in the frequency of allele B across most of Eurasia. In geographic variation, clines of this sort are gradual, and boundaries of population groups are therefore arbitrary. Abrupt changes are uncommon, and when they do occur they generally coincide with geographic barriers that hinder both migration and gene flow. Examples of such barriers include the Sahara Desert, the Himalaya Mountains, and the Timor Sea north of Australia.As can be seen in Figure 7.3, the frequencies of the blood group alleles A, B, and o vary greatly from one human population to another. The variations, however, do not necessarily coincide with other traits or with the groups recognized on the basis of morphology. Allele B, for example, reaches its highest frequency on mainland Asia, but is nearly absent from Native American populations or among Australian Aborigines. The frequency of allele A decreases from west to east across Asia and Europe. In Native American populations, allele A occurs mostly in Canada, and is mostly absent from indigenous Central or South American populations. The allele for blood group O has a frequency of 50% or more in most human populations, but its frequency approaches 100% in Native American populations south of the United States. African populations generally have all three of the alleles for ABO blood groups at levels close to worldwide averages.Since the clinal variation concept was introduced in 1939, it has become customary to describe human variation by drawing maps of one cline after another. In addition to cline maps of phenotypes and allele frequencies, the techniques of molecular genetics (such as the DNA marker techniques described in Chapter 3, p. 72) are now being used to study clines at the molecular level. Clinal maps can also be drawn for continuous traits, in which case average values for the trait are calculated in each population. To describe the geographic variation in Homo sapiens or any other species, we could draw one map showing clinal variation in average body height, another showing variation in skin color or hair form, and so on. The population genetics approach encourages the scientific study and description of populations, including studies on the origins and former migrations of populations.Figure 7.3The clinal distribution of alleles for the ABO blood groups in indigenous populations of the world. Indigenous populations are those that have lived for hundreds or thousands of years in approximately thesame region, to which they have had time to evolve adaptations.This includes Native Americans in the Western Hemisphere, Bantu and Xhoisan peoples in southern Africa, and Aborigines in Australia, but not the European colonists who came to these places after A.D. 1500.After the Holocaust (1933–1945), the fledgling United Nations felt the need to refute many Nazi claims about race. The result was the 1948 Statement on Race and Racism, written by a committee that included several prominent anthropologists and geneticists. The statement, which has been revised several times since 1948, correctly pointed out that nations,The distribution of allele Afrequency of A< 0.050.05–0.100.10–0.150.15–0.200.20–0.250.25–0.300.30–0.350.35–0.400.40–0.500.50–0.55The distribution of allele Bfrequency of B< 0.050.05–0.100.10–0.150.15–0.200.20–0.250.25–0.30©The distribution of allele ofrequency of o0.35–0.400.40–0.500.50–0.550.55–0.600.60–0.650.65–0.700.70–0.750.75–0.800.80–0.850.85–0.900.90–0.950.95–1.00 language groups, and religions have nothing to do with race, and that no group of people can claim any sort of superiority over another. The statement went further, however, to proclaim a new definition of race that replaced older, morphological definitions based on the inheritance of Platonic ‘ideal types’ with a new definition based on population genetics.Under the population genetics definition, a race is a geographic subdivision of a species distinguished from others by the allele frequencies of a number of genes. A race could also be defined as a coherent group of populations possessing less genetic variation than the species as a whole. Either definition means that blood group frequencies are now considered more important than skin color in describing race, and that races are groups of similar populations whose boundaries are poorly defined. It also means that one cannot assign an individual to a race without first knowing what interbreeding population that individual belongs to. ‘Race’ is no longer a characteristic feature of any individual, because allele frequencies, like average phenotype values, characterize populations only, not individuals. Allele frequencies are consequences of population membership; they cannot be used to assign someone to a particular population or group. For this reason, racially discriminatory laws cannot and do not use population genetics; such laws rely invariably on the older morphological definitions or the still older social definitions of race.Some writers maintain that racism is still contained in the population genetics race concept. They contend that studies that describe allele frequencies in geographic populations are merely reinscribing the racism of earlier concepts. Although far fewer people see racism in population genetics than in the earlier race concepts, some wish to go even further than the U.N. statement goes.The ‘no races’ concept. Some scientists went still further in rejecting the heritage of the racist past: in the 1960s, led by the British anthropologist M.F. Ashley Montagu (who had earlier contributed to the U.N. definition), they declared that they would not recognize races at all. Among their arguments, one of the most compelling is that race concepts have always been misused by racists of the past and that the only way to rid the world of racism was to reject the entire concept of race. History is replete with examples of slavery, apartheid, discrimination, genocide, and warfare between racial groups. It is therefore easy to argue that the naming of races has in past generations done far more harm than good.One stimulus to the ‘no races’ approach arises from the realization that there are no unique alleles or other genetic markers that could identify a person’s race. Races, like populations, differ in the frequency of various alleles but do not have alleles that belong exclusively to that group. Even differences in allele frequencies have become less pronounced as a result of the great increase in international travel and migration that has occurred especially since World War II. To a certain extent, human populations have always mated with one another whenever there has been geographic contact between them; this is one reason why human population groups do not differ more than they do and why neighboring populations are so often similar. Since the advent of the jet age, frequent migrations have allowed more extensive contact and more opportunities for mating between people of different genetic backgrounds than ever existed before. Such matings have always occurred and always will; they even occur in societies that have tried to outlaw them. This type of mating will slowly but inevitably diminish the differences in the mix of alleles (thegene pools) of populations, making it progressively more difficult to identify any significant differences between populations.The study of human variationAll studies of human variation run the risk of being misused or misinterpreted by racists. Nevertheless, there are many good reasons for studying human variation, and this study serves as the basis for the entire field of ‘human factors engineering.’ To take a simple example, the design of a passenger compartment (for automobiles, aircraft, etc.) must accommodate a certain range in the size, sitting height, arm length, and other dimensions of its possible occupants. These and other accommodations must take into account the total range of human variation, including all races and both sexes. In airline cockpits and similar enclosures, controls should be both visible and reachable by persons of different sizes. Moreover, these features are often matters of safety as well as comfort. Vehicle seat belts and airbags, sports equipment, surgical equipment, wheelchairs and similar aids, boots, helmets, kitchen counters, telephone receivers, gas masks, toilets, and doorways all need to accommodate the range of dimensions of the human body. Variation in other human characteristics (breathing rates, sweating) must also be considered in the design of space suits, diving equipment, respiratory equipment for fire fighting, or protective clothing for other situations. Most of the variation relevant for human factors engineering is found within each population group, including variation by age and sex; variation between human populations is generally minor by comparison.A further reason for studying genetic variation among human populations is that it can help us to understand evolution. Population genetics has helped us to recognize geographic patterns of disease resulting from natural selection acting on human populations. Studies of this kind can also help us to reconstruct the past history of particular human populations, or of the human species as a whole. In succeeding sections of this chapter we examine some of these studies.THOUGHT QUESTIONSTwentieth-century approaches to the description of human variation have in large measure been revolts against the earlier approaches. Against which of these earlier approaches was the ‘no races’ approach primarily directed? Against which earlier approach was the population genetics approach directed?African Americans more often have high blood pressure and more often die from their first heart attacks than do white Americans. How would you decide whether this is the result of a difference in genes, in diets, in the availability of medical care, or in the lasting effects of discrimination inU.S. society? If people in rural Africa seldom have heart attacks or high blood pressure, what possible hypotheses are falsified?To produce research results of the kind referred to in Thought Question 2, one must have a way of assigning an individual to a population group. How does one determine a person’s membership in a biological population? Is it sufficient to know that they live in a particular place? Will asking people to name the racial or ethnic group in which they claim membership (self-identification) produce biologically meaningful results?Population Genetics Can Help Us to Understand Human VariationThe geographic variation shown in Figure 7.3 deals with human blood groups. We know a lot about the genetic basis of blood groups, and a person’s blood group is easily determined, making blood groups good candidates for study by population geneticists. We now look in more detail at human blood groups and what their study has taught us about our own species.Human blood groups and geographyIn the days before reliable blood banks, blood transfusions were much riskier than they are today. Soldiers wounded in battle were generally treated in the field. If a transfusion was needed, it was done directly from the blood donor to a patient lying on an adjacent stretcher. Some transfusions were successful, but others resulted in death of the patient. Studies on the reasons for these different outcomes led to our knowledge of the existence of blood groups.ABO blood groups. During the Crimean war (1854–1856), a British army surgeon kept careful records of which transfusions succeeded and which did not. From his notes he was able to identify several types of soldiers, including two types that he called A and B. Transfusions from type A to type A were nearly always successful, as were transfusions from type B to type B, but transfusions from A to B or B to A were always fatal. Also discovered at this time was a third blood type, O, which was initially called ‘universal donor’ because people with this blood type could give transfusions to anyone. These results were put to immediate practical use in treating battlefield injuries.Karl Landsteiner, an Austrian pathologist who migrated to the United States, discovered the reason for these distinctions. Persons with blood type A make a carbohydrate of type A, which appears on the surfaces of their blood cells. Persons with blood type B make a carbohydrate of type B; persons with type AB make both type A and B carbohydrates; and persons with blood type O make neither of these carbohydrates. The A and B carbohydrates are also called antigens because they are capable of being recognized by the immune system (see Chapter 15). The immune system of each individual also makes antibodies against the blood group antigens that their own body does not make. In a person receiving a transfusion with incorrectly matched blood, these antibodies bind to the type A or B antigens, causing the blood cells to clump together within the blood vessels (Figure 7.4), often with fatal results. For explaining these immune reactions, Landsteiner received the Nobel Prize in 1930.The A and B antigens allow all people to be classified into the four blood groups A, B, AB, and O. These blood groups are controlled by a gene that has three alleles: allele A is dominant and it contains information for producing antigen A (its phenotype); allele B is dominant and it contains information for producing antigen B (its phenotype); allele o is recessive and it functions as a ‘place-holder’ on the DNA but produces neither functional antigen. The AA and Ao genotypes both produce antigen A and are therefore assigned to blood group A. Likewise, both BB and Bo genotypes produce antigen B and result in the B blood type. Genotype oo produces neither A nor B antigens, which results in the O blood type (universal donor). Finally, genotype AB allows both alleles A and B to produce their respective antigens, resulting in the AB blood type. When they occur together, the A and B alleles are said to be codominant because the heterozygote shows both phenotypes.For the purpose of matching blood donors and recipients, any person who shares your blood type is a good donor. It is therefore possible to collect blood in advance from many donors, sort the blood by blood type, and store it under refrigeration for use in an emergency. It is ironic that the doctor who developed this concept, an African American named Charles Drew (1904–1950), was denied its full benefits because many hospitals at the time kept separate blood banks for whites and nonwhite patients, a practice that has no biological foundation. Because the chemical composition of the allele products does not vary, type A antigen from an African American is identical to type A antigen from a Native Ameri-can or from anyone else. A person with blood type A is therefore a good donor for almost any other person with blood type A.Other human blood groups. Karl Landsteiner also discovered several other blood group systems that are totally independent of ABO. One such system, called the Rh system, actually has three genes located very close together on the same chromosome: the first gene has alleles C and c, the second has alleles D and d, and the third has alleles E and e. Unlike the ABO system, in which alleles are codominant, c, d, and e are recessive to C, D, and E. In all, there are eight phenotypic possibilities, of which phenotype cde (genotype ccddee, homozygous recessive for all three genes) is sometimes called Rh-negative and the others Rh-positive. The CDe phenotype is the most frequent phenotype in most populations, except in Africa south of the Sahara, where cDe predominates. The Rh-negativeblood typegenotypeantigenantibodies maderecipientdonorABABOAAA or AoAanti-BABBB or BoBanti-ABABABA + Bneither anti-A nor anti-BABuniversal recipientOooneitherboth anti-A andanti-BOuniversal donorphenotype cde is the second most common Rh phenotype in Europe and Africa, but is rare elsewhere.Problems arise when a mother with the cde Rh-negative phenotype is pregnant with a baby who has a dominant C or D or E allele and is therefore Rh-positive. In this case, the mother makes antibodies against the C, D, or E antigens on the baby’s blood cells, especially in response to the tearing of blood vessels during the process of birth. Because these antibodies are made at the end of pregnancy, they usually don’t affect the first Rh-positive fetus that the mother carries. However, once these antibodies have been made, the mother’s immune system attacks any subsequent pregnancy with an Rh-positive fetus, destroying many of the fetus’ immature red blood cells, which can cause the death of the fetus (Figure 7.5). This problem can now be prevented by giving the Rh-negative mother gamma globulin (e.g., RhoGAM) at the time of the birth of any Rh-positive child; the globulin inhibits the formation of antibodies against Rh antigens, thereby protecting future pregnancies.Separate from the ABO and Rh blood group systems are an MN system (with M most frequent among Native Americans and N among Australian Aborigines), a Duffy blood group system (with alleles Fy, Fya, and Fyb), and many others.Geographic variation in blood group frequencies. We saw earlier that the alleles for the ABO blood groups vary in frequency in different geographic locations (see Figure 7.3). Table 7.1 shows how the major geographic subgroups of Homo sapiens differ in the frequencies of various blood groups and other genetic traits. It is important to remember thatFigure 7.5Rh incompatibility arising in an Rh-negative mother pregnant with an Rh-positive child.FIRST Rh+PREGNANCY When an Rh-negative mother has her first Rh-positive pregnancy, the baby's C, D, or E antigens enter the mother's bloodstream during placental abruption after birth. or SECOND Rh+PREGNANCY Antibodies produced after the first pregnancy can endanger any subsequent Rh-positive fetus if Rh protective measures are not taken–maternal uterus placental sac Rh+Fetal C, D, or E antigens Anti-Rh antibodies, according to Rh+ fetus allele frequencies characterize populations only, not individuals. No blood group is unique to any population, so a person’s blood type cannot identify them as a member of any population.Frequencies of blood group alleles also vary on a smaller geographic scale. This is especially true among rural people who remain in their native villages or districts all their lives. The geneticist Luigi Cavalli- Sforza has documented variation in the ABO, MN, and Rh blood group frequencies from one locality to another across rural Italy. Similar results have been observed in rural populations in the valleys of Wales, in African Americans from city to city across the United States, and among the castes and tribes of a single province in India. These studies emphasize the hazards of assigning all people in a single country to a single population, especially when cultural barriers discourage random mating. However, populations that have become more mobile experience less of this microgeographic variation. As stated earlier, these are variations in allele frequencies and therefore can not be used to establish clear-cut boundaries between populations.Isolated populations and genetic driftIn large, randomly mating populations in which selection and migration are not operating, the frequencies of the genotypes in the population tend to remain the same. This principle, which operates in all sexually reproducing species, is called the Hardy–Weinberg principle, and the predicted equilibrium is called the Hardy–Weinberg equilibrium (Box 7.2). One of the criteria for a Hardy–Weinberg equilibrium is that the population be large. In small populations, allele frequencies tend to vary erratically, in unpredictable directions, from the expectations of the Hardy–Weinberg equilibrium. This phenomenon, called genetic drift, isdefined as changes in allele frequencies in small to medium-sized populations due to chance alone.The original model of genetic drift dealt with populations that remained small all the time, but other types of genetic drift were found to apply in particular situations. For example, if a large population became temporarily small and then large again, the random changes in allele frequencies that occurred when the population was small—the bottleneck— would be reflected in the allele frequencies of subsequent generations. This bottleneck effect is shown in Figure 7.6. Another type of genetic drift occurs if a small number of individuals become the founders of a new population. The allele frequencies in such a new population—whatever its subsequent size—will reflect the allele composition of this small group of founders, an influence known as the founder effect.Several cases of genetic drift have been studied in isolated human populations. One well-studied example concerns the German Baptist Brethren, or Dunkers, a religious sect that originated in Germany during the Protestant Reformation. Forced to flee their native Germany, a few dozen Dunkers came to Pennsylvania in 1719 and started a colony that grew to several thousands and spread to Ohio, Indiana, and elsewhere. Because their strict religious code forbids marriage outside the group, they have remained a genetically distinct population.Allele frequencies among the Dunkers have been influenced by genetic drift, particularly by the founder effect. If the Dunkers were a representative sample of seventeenth-century German populations, we would expect similar allele frequencies to those of present-day German populations derived from the same source. If, however, natural selection had changed the Dunker populations as the result of adaptations to their new location, then we would expect their allele frequencies to come closer to those of neighboring populations of rural Pennsylvania. Neither of these predictions is correct. Allele frequencies among the Dunkers differ from populations of both western Germany and rural Pennsylvania in a number of traits that havebeen studied. Blood group B, for example, hardly occurs at all among the Dunkers, although the frequency of the B allele is around 6–8% in most Europeanderived populations, including those of both Germany and Pennsylvania. Other genetically determined traits show similar patterns, including the nearly total absence of the Fya alleleFigure 7.6The bottleneck effect, a form of genetic drift that originates when populations are temporarily small.(from the Duffy blood group sys-tem) among Dunkers. The explanation that best agrees with the data is that the original founder population, known to have been made up of only a few dozen individuals, happened not to include anyone carrying Fya orallele frequencies:= .20= .80BEFORE THE BOTTLENECKan initially large population (actually much larger than shown here)allele frequencies:= .40= .60BOTTLENECKtemporarily smaller population: allele frequencies can drift in random directionsallele frequencies:= .40= .60AFTER THE BOTTLENECKpopulation once again large, but allele frequencies now reflect genetic drift that happened when the population was small the allele for blood group B. Additional alleles may have been lost by genetic drift while the population remained small. The result was a population that derived its allele frequencies from the assortment of alleles that happened to be present in the founders. We can test this assumption by looking for the rare Dunkers who do possess an allele such as Fya. In every case that has been investigated, the occurrence of such an allele among the Dunkers can be traced to a person who joined the group as a religious convert within the last few generations.Because they are genetically isolated, except for occasional religious conversions, the Dunkers have kept a unique combination of unusual allele frequencies. In the absence of blood group B, they resemble Native American populations; in the absence of Fya, they resembleBOX 7.2 The Hardy–Weinberg EquilibriumThe Hardy–Weinberg principle can be stated as follows:In a large, randomly mating population characterized by no immigration, no emigration, no unbalanced mutation, and no differential survival or reproduction (that is, no selection), the frequencies of the alleles (genotypes) tend to remain the same.Allele frequencies are fractions of the total number of alleles present. If a population of 500 individuals (or 1000 alleles at a single genetic locus) contains 400 alleles of type A and 600 alleles of type a, then we say that the frequencies of the two alleles are 0.40 and 0.60 respectively, or 40% and 60% of the total number of alleles in the gene pool. At a given locus, the allele frequencies always add up to 1, or 100% of the population’s gene pool.Under the conditions specified in the Hardy–Weinberg principle, as stated above, there is a simple equilibrium of unchanging allele frequencies. Let us consider the case of a gene locus that contains two alleles, A and a. If the frequency of allele A is called p and the frequency of allele a is called q (where p + q = 1), then the equilibrium frequencies of all three diploid genotypes is given by the Hardy–Weinberg formula:Genotypes AA Aa aaFrequencies p2 + 2pq + q2 = 1This formula predicts that the frequency of the homozygous dominant genotype AA will be p2, the frequency of the heterozygous genotype Aawill be 2pq, and the frequency of the homozygous recessive genotype aa will be q2.To show that these equilibrium frequencies remain stable over successive generations and do not tend to change in either direction, consider the production of gametes in a population already at equilibrium. All of the gametes produced by the dominant homozygotes AA carry allele A, so the frequency of A gametes from AA homozygotes is p2. Half of the gametes produced by the heterozygotes Aa also carry allele A, so the frequency of A gametes from heterozygotes is half of 2pq, which equals pq. The total proportion of A gametes is thus p2 + pq. We can now use simple algebra, separating out the common factor and then applying the equationp + q = 1 to calculate the frequency of A gametes: Frequency of A gametes:p2 + pq = p(p+q)= p(1)= pIn similar fashion, the proportion of gametes carrying allele a is equal to pq (the other half of 2pq) from the heterozygotes plus q2 from the recessive homozygotes aa.Frequency of a gametes:pq + q2 = (p + q)q= (1)q= qSo the frequency of A and a gametes corresponds to the frequency of A and a alleles.African populations. In most traits, however, their derivation from a European source population is evident. These findings show that population resemblances based on a single blood group or gene system may often be misleading, and that distinctions among human populations, if used at all, should be based on a multiplicity of genetic traits.The bottleneck effect has been used as a hypothesis to explain the near-total absence of blood group B among Native Americans and of cde (in the Rh blood groups) among Pacific Islanders. When the ancestors of these people first migrated from Asia, the random changes in allele frequency that occurred when the groups were small gave rise to distinct, isolated populations whose allele frequencies differed from those of the ancestral populations. Genetic drift of this kind would apply primarily toCombining the gametes in all possible combinations (to simulate random mating) produces the following results:Female gametesGametes Frequencies Genotypes FrequenciesTaking the resulting genotypes from the chart above (and adding the two heterozygous combinations together), we obtain:AA Aa aap2 + 2pq + q2 = 1This is the same equation that we started with, which shows that the frequencies have not changed. It can also be shown that a population that does not start out at equilibrium will establish an equilibrium in a single generation of random mating.Notice all the assumptions of the model: the population must be closed to both emigration and immigration, and there must be no unbalanced mutation and no selection. The population must be large enough to permit accurate statistical predictions, and the population members must mate at random. In reality, most natural populations are subject to mutation, selection, and nonrandom mating(including inbreeding), and most usually experience emigration and immigration as well. The Hardy–Weinberg model, in other words, describes an idealized situation that is seldom realized in practice. The Hardy–Weinberg equilibrium is important to population genetics as an ideal situation with which real situations can be compared; if a population is not in Hardy–Weinberg equilibrium, one can ask why and then seek to measure the extent of the deviation from equilibrium. The same procedure is followed in other sciences as well. For example, ‘freely falling bodies without air resistance’ are an ideal situation in physics, and air resistance can be measured as a deviation from this ideal.The Hardy–Weinberg equation is useful in estimating allele frequencies for traits controlled by a single gene. For example, if a population of 1000 has 960 individuals showing the dominant phenotype (such as normal pigmentation) and 40 displaying the recessive phenotype (such as albinism), then q2, the proportion of homozygous recessive individuals, is equal to 40/1000, or 0.04. From this, we can calculateq = 0.04 = 0.2.From the fact that p + q = 1, we can calculate p = 1 – q. Substituting the value of 0.2 that we found for q gives us p = 1 – 0.2 or p = 0.8. Then the proportion of homozygous dominantsin the population is p2 = (0.8)2 = 0.64 and the proportion of heterozygous individuals is 2pq = 2(0.8)(0.2) = 0.32.Figure 7.7A family tree of human populations constructed on the basis of mitochondrial DNA sequences. ‘Genetic distance’ refers to the fraction of mitochondrial DNA sequence not shared by two populations, so that a fork at a genetic distance of 0.006 means that the populationsgroups of people, like the Polynesians or Native Americans, whose founder populations were initially small. The effects of genetic drift are minimal in the larger and more widespread population groups of Africa, Europe, and mainland Asia.Reconstructing the history of human populationsAllele frequencies and DNA sequences in modern populations can be used as clues to their evolutionary origins. For example, American molecular biologist Rebecca Cann and her co-workers studied mitochondrial DNA sequences in samples from over 100 human populations. Mitochondria are organelles in the cytoplasm of eucaryotic cells (Chapter 6, p. 170)that produce much of the cell’s energy and share 99.4% of their mitochondrial DNA sequences.AfricanCaucasoidPOPULATIONMbuti PygmyW. African Bantu Nilosaharan San (Bushmen) EthiopianBerber, N. AfricaS.W. Asian Iranian European Sardinian IndianS.E. Indian Lapp Uralic Mongolthat also contain small strands of DNA independent of the DNA in the nucleus. Mitochondrial DNA is transmitted only maternally, from mother to both male and female offspring. Sperm from the father contain almost no cytoplasm and do not transmit mitochondrial DNA. Because mitochondrial DNA is smaller than chromosomal DNA in the nucleus, it is easier to sequence and is thus ideal for tracing evolutionary patterns. On the basis of these DNA sequences, Cann and her colleagues proposed a family tree of human populations using a maximum-parsimony computer model: of all possible family trees, the one shown in Figure 7.7 requires fewer mutational changes to have occurredNorth EurasianSoutheastAsianNortheastAsianAmericanTibetan Korean Japanese AinuN. Turkic Eskimo ChukchiS. AmerindC. AmerindN. AmerindN.W. Amerind So. Chinese Mon Khmer Thai Indonesian Malaysian Filipino Polynesian Micronesian Melanesian New Guinean Australianthan for any other tree. Another researchteam, headed by Luigi Cavalli-Sforza, used alleles of 120 genes to study the genetic similarities among 42 populations representing all the world’s major population groups and many small ones as well. The findings of these two studies (and others) support the hypothesis of a divergence in the distant past between African and non-African populations, with the non-African populations later splitting into North Eurasian and Southeast Asian subgroups (see Figure 7.7). Australian Aborigines and Pacific Islanders are descended from the Southeast Asian subgroup, whereas Caucasians (Europeans, West Asians) and Native Americans (Amerind) are both descended from the North Eurasian group, which also includes Arctic peoples. The groups suggested by this study are geographically coherent and confirm certain well-documented patterns of0.030 0.024 0.018 0.012 0.006 0.000genetic distancemigration. Existing linguistic evidence also matches these groupings, except for a few cases of cultural borrowing, which can be documented historically. Cavalli-Sforza’s group estimates, largely on the basis of archaeological evidence, that the split between African and non-African populations took place 92,000 or more years ago. Other estimates have placed this split much earlier, back to the time of Homo erectus. The spread of human genes outward from Africa was either a very early event, or perhaps there were several such diffusions.Studies such as those we have just described have sometimes been criticized for not being politically correct or for ‘reinscribing racism.’ A related criticism of the methodology is that geneticists with no training in anthropology are often tempted to lump together people who live close together even if there is good evidence that they have been historically and culturally separate. In other cases, people may maintain contact across considerable distances with other people who are culturally similar and speak the same language, and may consider themselves as belonging to the same group, even if population geneticists list them as separate because of the geographical distance between them. Although a good deal of interbreeding between groups always takes place, people more often choose their mates from what they consider as their own group. In order to assess what population groups actually exist (or existed historically), population geneticists need to cooperate with anthropologists familiar with the people being studied.Paleontological and anthropological studies show that Homo sapiens has always been geographically widespread, with early populations spread across three continents, from Indonesia to Zambia and Western Europe. The earlier species Homo erectus was also geographically widespread. Despite this geographic spread, however, neighboring populations have always maintained genetic contact. Adaptation to local environments has caused populations to evolve geographic differences from one another, while matings between populations has maintained enough gene flow to prevent populations from becoming even more different. These two opposing tendencies form the basis for what American anthropologist Milford Wolpoff has called the multiregional model of the human species, which asserts that human populations have always maintained genetic contact with one another despite the differences resulting from local adaptation. The genetic contact maintains all human populations as one species, while the local adaptations have prevented geographic uniformity.The study of allele frequencies has also been used to determine the ori-gins of particular groups of people. One such study, for example, showed that Koreans are derived from a group that includes the Mongolians and Japanese but not the Chinese. Also, several studies have provided evidence for a Middle Eastern contribution (perhaps via Phoenecian sailors) to the populations of both Sicily and Sardinia. Studies of the Native Americans have shown that a minimum of three separate migrations were responsible for populating the Western Hemisphere, and more recent studies show that the situation is far more complex than this.How did the adaptations come about that led to the various population differences in allele frequencies? The next two sections attempt to provide some of the answers to this question.THOUGHT QUESTIONS1 Random mating in a sexual species means that any two opposite-sex individuals have the same chance of mating as any other two. If there are a million individuals of the opposite sex, then each should have an identical chance (one in a million) of being chosen as a mate. Do you think human populations mate at random? Why or why not?Is there ever a real population (of any species) in which the conditions specified by the Hardy–Weinberg equilibrium exist? How close do particular populations come?If language has nothing to do with race, why do you suppose that researchers attempting to reconstruct the past history of human populations use linguistic evidence?Malaria and Other Diseases Are Agents of Natural SelectionAs any species evolves, biological differences among its populations arise largely through natural selection. Diseases are among the selective forces that can result in genetic differences among populations. In this section we consider some genetic traits that confer partial resistance to malaria. In malaria-ridden areas, natural selection acts to increase the frequency of alleles that confer partial resistance to malaria while decreasing the frequency of alleles that leave people susceptible to malaria. Many other selective forces have also operated over the course of human history, but resistance to malaria provides a series of well-studied examples.New traits are produced by mutation (see Chapter 3, pp. 67–69) and are then subjected to natural selection, a process in which many traits die out in populations. The traits that survive natural selection are adaptive traits, or adaptations (Chapter 5), that is, traits that increase a population’s ability to persist successfully in a particular environment. A good deal of human variation consists of adaptations that have resulted from natural selection operating over time, disease being a significant agent of that selective process.MalariaOn a worldwide basis, malaria causes over 110 million cases of illness each year and causes close to 2 million deaths, more than most other diseases. (Only malnutrition and tuberculosis cause more deaths each year, and measles causes about the same number.) Malaria also has a greater impact than most other diseases on the average human life expectancy because most of its victims are young, so that many more years of life are lost for each death that occurs. Malaria is more prevalent in tropical and subtropical regions than in temperate climates. The threat of malaria has largely been eliminated in the industrially developed countries through mosquito eradication programs and the draining of swamps, but as late as the first half of the twentieth century, malaria claimed many thousands of victims in Florida, Louisiana, Mississippi, and Virginia.Historical and anthropological evidence confirms that malaria was rare (and therefore not a significant selective force) before the invention of agriculture. Even today, the disease is rare in undisturbed forests or in hunting-and-gathering societies. The clearing of forests for agricultural use opens up more swampy areas, and the building of irrigation canals or drainage ditches creates additional pools of stagnant water. The mosquitoes that carry malaria breed best in stagnant water open to direct sunlight. Agriculture therefore did much to change, in unintended directions, the agents of death (and thus the selective pressures) that act on human populations.Life cycle ofPlasmodium. Malaria is caused by one-celled protozoan parasites belonging to the genus Plasmodium (kingdom Protista, phylum Sporozoa), which live in human blood and liver cells. Of the four species of Plasmodium that cause malaria, Plasmodium falciparum is the most virulent. All species of Plasmodium have a complex life cycle, spending different parts of their life cycle in two different host species, mosquitoes and humans. The Plasmodium sexual stages (male and female gametocytes) are intracellular parasites that inhabit human red blood cells. When a female mosquito of the genus Anopheles is ready to lay her eggs, she first takes a blood meal from a person during which she ingests large numbers of red blood cells. (Mosquitoes rarely bite otherwise.) If the red blood cells contain Plasmodium, the male and female gametocytes combine in the mosquito’s gut to form zygotes (fertilized eggs). The zygotes develop asexually through several stages within the mosquito, culminating in the infective forms (sporozoites), which migrate into the mosquito’s salivary glands (Figure 7.8).The mosquito’s thin mouthparts function like a tiny soda straw or hypodermic needle. Shortly before consuming a blood meal, the female mosquito injects her saliva into her victim. The saliva contains anticoagulants that prevent the human blood from clotting inside the mosquito’s mouthparts. When the mosquito injects saliva into a new human host, any sporozoites present in her salivary glands are injected along with it. These sporozoites enter the human bloodstream and are taken up by the liver. Each parasite then develops into thousands more, which may remain in the liver for years. Some parasites periodically escape from the liver into the bloodstream and invade the red blood cells. The parasites reproduce asexually within the red blood cells, producing the disease symptoms. The parasites digest the cell’s oxygen-carrying hemoglobin molecules, and one stage also ruptures the red blood cells. Any impairment of the ability of the blood to carry oxygen to the body’s tissues is called an anemia; all anemias leave their victims run-down and weakened. In malaria, the anemia is caused by destruction of both the hemoglobin and the red blood cells. Cell rupture also brings on fevers, headache, muscular pains, and liver and kidney damage. Within a given host, the asexual cycle of Plasmodium continues again and again until the patient either recovers or dies. In the red cells, the parasites can also develop into the sexually reproducing gametocyctes, which may be picked up by another mosquito in its next blood meal, spreading the disease.Figure 7.8Life cycle of the malaria parasite Plasmodium.Sickle-cell anemia and resistance to malariaOne of the symptoms of malaria is anemia. There are many other types of anemia. A very serious type was first discovered in 1910 by a Chicago physician named Charles Herrick. This strange and usually fatal disease also produced abnormally shaped red blood cells that sometimes resembled sickles. For this reason, Herrick called the disease sickle-cell anemiaMature infective stages (sporozoites) escapeWhen the mosquito bites another human, sporozoites are injected with bite. from intestine and migrate to the mosquito salivary glands.sporozoites salivary glandFollowing a mosquito bite, the infective stages of the parasite (sporozoites) quickly migrate through the blood into the person’s liver.Fertilization and development take place in the mosquito’s intestine.The parasite reproduces asexually in liver cells, bursting the cell and releasing parasites into the blood.Female mosquito takes up gametocytes with blood meal.gametocytes female maleSexual stages (gametocytes) develop in red blood cells.Parasites reproduce asexually in red blood cells, bursting the red blood cells and causing cycles of fever and other symptoms. Released parasites infect newred blood cells.A simple blood test was soon devised to test for the condition: a glass slide containing a bowl-shaped depression is used, and a drop of the patient’s blood is placed inside the depression. A ring of petroleum jelly is placed around the margins of the depression and a cover glass is then applied, forming an airtight seal. As the red blood cells use up the available oxygen in the depression, the oxygen level decreases. Under these conditions, the red blood cells of a person with sickle-cell anemia assume their characteristic sickle-like shape, while normal red blood cells retain a circular biconcave shape (Figure 7.9). This blood test also allows the recognition of heterozygous carriers, a small percentage of whose blood cells sickle while the rest remain round.Normal and abnormal hemoglobins. Sickle-cell anemia is caused by an abnormality in the molecules (called hemoglobin) that carry oxygen within the red blood cells. The hemoglobin molecule consists of four protein chains (two each of two different proteins) surrounding a ringlike ‘heme’ portion. Suspended in the middle of this ring is an iron atom that can bind one oxygen molecule (O2), which gives hemoglobin its ability to carry oxygen and also its red color. The alteration of a single amino acid, number 6 in one of the protein chains, is responsible for sickle cell anemia. Normal adult hemoglobin (hemoglobin A) has glutamic acid at this position in the chain, whereas sickle cell hemoglobin (hemoglobin S) has valine. This small change alters the shape of the hemoglobin S molecule and puts pressure on the circular heme portion of the molecule, causing hemoglobin S to carry less oxygen than hemoglobin A. When not carrying oxygen, hemoglobin S molecules they are stickier than hemoglobin S. normal hemoglobin. When the oxygen concentration in the blood is low, such as during physical exertion, the hemoglobin S molecules stick to each other and also to the interior of the red blood cell membrane, deforming the cells into the characteristic sickle shape. The difference in proteins is hereditary and is caused by a codon change in the hemoglobin gene in the DNA. Figure 7.9 Normal red blood cells and red blood cells from a patient with sickle cell hemoglobin. Sickle cell disease is inherited as a simple Mendelian trait. People who die from sickle cell disease are always homozygous, and their parents are almost always heterozygous, as are various siblings and other relatives. The gene for hemoglobin is called Hb, and the different alleles are indicated by superscripts: HbA is the allele for normal hemoglobin and HbS is the allele for sickle cell hemoglobin Sickle cell hemoglobin are black people of African descent. Evidence from African populations also shows a high frequency of the sickle cell allele, up to 25% in certain populations. In homozygous (HbSHbS) individuals, all red blood cells become deformed at low oxygen concentrations, as is common with strenuous exertion. Heterozygous (HbAHbS) individuals have both types of hemoglobin, and about one percent of their red blood cells may become crescent-shaped, while the rest are normal in shape. Because both alleles produce a phenotypic result in heterozygotes, they are codominant, as we described above in relation to blood type AB. Symptoms of sickle cell anemia. Most of the debilitating symptoms of the disease are a consequence of sickled deformed cells caused by exertion. The smallest blood vessels, the capillaries, have a diameter slightly larger than the diameter of the blood cells. Due to their sickle shape and altered diameter, sickle cells cause resistance to flow in the capillaries and thus disrupt microcirculation. In most organs of the body, impaired microcirculation further reduces oxygen levels (hypoxia), immediately leading to a very painful sickle cell crisis. These crises begin in childhood. Damaged cells accumulate in the articular capillaries, causing painful inflammation. Sickle cells are also more easily broken down and destroyed than normal round cells, resulting in reduced oxygen-carrying capacity (anemia). Anemia and impaired blood flow lead to tissue damage in many organs and eventually death (Figure 7.10). In African populations, death of HbSHbS homozygotes usually occurs before adulthood, but survival to reproductive age is now increasingly common in the United States and the Caribbean. Decreased red blood cell counts and sickle cell crises also occur in heterozygotes, but not as severely. Population genetics of sickle cell anemia. Realizing that sickle cell disease in the United States and Jamaica was largely confined to people of African descent, geneticists began to study other populations. Using the blood test described earlier in this chapter, the researchers examined the frequency of the hemoglobin S allele in many African and Eurasian populations. In much of tropical Africa, the researchers found remarkably high frequencies of the HbS allele, up to 25% or more. At first, this seemed puzzling, since sickle cell disease is almost always fatal before childbearing years. An allele whose effects are lethal in the homozygous form should have been eliminated by natural selection long ago, since people with sickle cell children would have fewer children who would reach reproductive age. Sickle cell allele frequency maps were generated. These maps and other evidence indicated that areas where the sickle cell allele was common were also areas with a high incidence of malaria, particularly of the Plasmodium falciparum variety (Figure 7.11A and B). Subsequent research confirmed the fundamental fact that the HbS allele, even in the heterozygous form, confers significant resistance to the most virulent form of malaria. Tests in which volunteers were exposed to Anopheles mosquitoes showed that the mosquitoes were much less likely to bite HbA/HbS heterozygous individuals than HbA/HbA homozygous individuals. Tests for the Plasmodium falciparum parasite have shown that it thrives in the red blood cells of HbA/HbA people, who almost always develop a severe case of malaria after infection. However, when HbA/HbS heterozygotes or HbS/HbS individuals with sickle cell disease are infected with Plasmodium falciparum, their malaria symptoms are mild and they recover quickly because the parasite is unable to complete its asexual cycle in their sickle cells. The protection conferred by the HbS allele against malaria is sufficient to explain its persistence in populations with a high incidence of malaria. Therefore, hemoglobin S decreases the fitness of homozygotes that cause sickle cell anemia, but increases the fitness of heterozygotes for areas where malaria occurs. In this way, malaria acts as a tool of natural selection and has a dramatic impact on the allele frequencies of populations. In addition to hemoglobin A and hemoglobin S, other genetic variants of hemoglobin have been discovered. Some of these, such as HbC, also occur mainly in malarious areas and are thought to confer some resistance to malaria. Fig. 7.10 Development of the consequences of the HbS mutation in the hemoglobin gene. A small change in one gene can have many phenotypic consequences. Single base pair change in DNA Substitution of valine for glutamic acid at position 6 of hemoglobin Altered shape of the hemoglobin molecule Changes in the cytoskeleton of red blood cells Sickling of red blood cells destroys many sickle cells Anemia Weakness and fatigue Sickle cell crowding impairs health Blood flow affects blood supply to many organs Growing cells accumulate in the spleen Enlargement of the spleen Increased growth of the bone marrow "bump" of the skull Enlargement of the heart Impairment of mental functions Reduced physical development Damage to heart muscles Heart failure Damage to lung organs Abdominal pain Spleen tissue becomes fibrous Figure 7.11 Distributions in the Eastern Hemisphere, the genetic conditions of Plasciparum malaria and several that precede them protection .
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0.05-0.20 Other genetic characteristics that protect against malaria Sickle cell anemia is not the only heterozygous disease that protects against malaria. Two others are thalassemia and G6PD deficiency. thalassemia In many countries bordering the Mediterranean Sea (including Spain, Italy, Greece, North Africa, Turkey, Lebanon, Israel and Cyprus), many people have suffered from another type of debilitating anemia known as thalassemia (meaning "sea blood" ). means Greek). The disease also occurs further east, particularly in Southeast Asian countries such as Laos and Thailand (Figure 7.11C). Thalassemia is characterized by a reduced amount of one or more protein chains in the hemoglobin molecule. Disease occurs with more severe homozygous frequency, often fatal 0.01-0.05 <0.01 occurrence of P. falciparum malaria (B) Hb frequencys allele©Frequency of alleles for thalassemia(actually the sum for alleles that lead to several different forms of thalassemia)Frequency of allele for G6PD deficiencyform called thalassemia major and a less severe heterozygous form called thalassemia minor. Red blood cells containing nonfunctional hemoglobin are destroyed in the spleen, producing anemia.The symptoms of thalassemia vary, but all forms result in some decrease in oxygen transport in the blood. The bone marrow compensates by overproducing red blood cells, and this overproduction robs the body of much-needed protein and results in stunted growth and smaller stature.Populations in which thalassemia occurs can now be screened for the genotypes that cause the disease, and genetic counseling can be provided to those found to carry the trait. Screening programs and newer methods of treatment have greatly reduced the problems caused by this disease in Italy, Greece, and elsewhere in the Mediterranean.The geographical distribution of thalassemia follows closely the distribution of malaria in countries where sickle-cell anemia is infrequent or absent. For this reason, it has long been suspected that thalassemia confers a protective resistance to malaria, similar to that caused by sickle-cell anemia. The evidence is indirect: if heterozygous individuals (those with thalassemia minor) did not have some selective advantage such as malaria resistance, then the deaths caused by thalassemia major would have caused the genes for this trait to die out long ago.G6PD deficiency. Blood sugar (glucose) is normally broken down within each cell in a series of reactions that begin with the formation of glucose 6-phosphate. Most of the glucose 6-phosphate is broken down into pyruvate (see Chapter 10, pp. 349–350) in a series of energy-producing reactions, but some is also used to make ribose (the sugar used in RNA) and to make reducing agents such as NADPH and glutathione. The removal of two hydrogen atoms from the glucose 6-phosphate molecule requires the enzyme glucose 6-phosphate dehydrogenase (G6PD). There are many people who have too little of this enzyme, a condition known as G6PD deficiency, or favism. G6PD deficiency results from a mutation in the gene that encodes the G6PD enzyme.Under many or most conditions, people with G6PD deficiency remain perfectly healthy, but they occasionally suffer from an anemia in which the red blood cells rupture, spilling their hemoglobin, which then becomes physiologically useless but easy to detect by simple lab tests. This type of anemia, which is potentially fatal, can occur in G6PD-deficient people as a reaction to certain drugs (aspirin, quinine, quinidine, chloroquine, chloramphenicol, sulfanilamide, and others), in response to certain illnesses, or after eating fava beans (Vicia faba), a common legume of the Eastern Mediterranean and Middle East. The anemia may also exist chronically in a nonfatal form in people with G6PD deficiency. G6PD deficiency has been shown to offer protection against P. falciparum malaria. It affects some 10 million people, and is thus the most common disorder offering protection against malaria. Most importantly, heterozygous carriers of the deficiency are also malaria-resistant, but theexact mechanism of the resistance has yet to be worked out.G6PD deficiency occurs mostly in Mediterranean populations from Greece to Turkey and from Tunisia to the Middle East, and among Sephardic Jews. It also occurs south of this area into Africa and eastward across Iran and Pakistan to Southeast Asia and southern China (Figure 7.11D). The Greek mathematician Pythagoras may have suffered from this disorder, for his aversion to beans (one of the triggers of anemia in G6PD-deficient people) has become legendary. Pythagoras founded a religious cult in which the avoidance of beans was an important belief. Opponents of his cult once captured Pythagoras by chasing him toward a bean field, which they knew he would not cross.Population genetics of malaria resistancePolymorphism is the term used to describe a condition in which two or more alleles of the same gene are known in a given population at frequencies higher than the mutation rate. (This last restriction means that the alleles were inherited and could not all simply be the result of new mutation.) Polymorphism is a characteristic of the population, not of individuals; an individual may bear only one, or at most two, of the many alleles present in the population. Some alleles of polymorphic genes have harmful effects when homozygous, but they persist in populations because the same alleles also confer some important benefit (such as malaria resistance) when heterozygous. If the polymorphism persists for many generations, it is likely to be a balanced polymorphism. Balanced polymorphism arises when the homozygous genotypes suffer from some selective disadvantage or reduction in fitness, while the heterozygotes have the maximum fitness. For example, in a country in which malaria is present, HbAHbA homozygotes have lower fitness because they are susceptible to malaria, and most HbSHbS homozygotes die young from sickle-cell anemia. The HbAHbS heterozygotes have maximal fitness because they are malaria-resistant and because they have enough normal red blood cells for them not to suffer from fatal sickle-cell anemia. Under conditions like these, natural selection brings about and perpetuates a situation in which both alleles persist.The selection by malaria for genetic traits that offer resistance to it is at least as old as the open, swampy conditions (ideal for the breeding of mosquitoes) brought about by agriculture in warm climates. Evidence for this exists in the form of human bones found at a Neolithic archaeological site along the coast of Israel. Cultural remains found at this site show that it was an early farming community, one of the first in the area. Pollen analysis shows the presence of many plants characteristic of swampy areas. Some of the bones show characteristic increases in porosity (due to the increased production of red blood cells in the bone marrow) indicative of thalassemia.Other diseases as selective factorsHereditary diseases that confer some advantage in the heterozygous state are not confined to those that protect against malaria. In European populations of past centuries, tuberculosis, an infection caused by a bacterium called Mycobacterium tuberculosis, was an important force of selection, especially in crowded cities from the Middle Ages to the early twentieth century. One scientist has proposed that people heterozygous for the alleles that cause cystic fibrosis (an inherited lung disorder discussed in Chapter 3, p. 77) were protected against tuberculosis; they therefore survived tuberculosis epidemics in greater numbers than did people without cystic fibrosis alleles. As the heterozygotes increased in number, some of them married one another, and, on average, one out of four of their children became afflicted with cystic fibrosis. What about the geographic variation in blood groups and other genetic traits? There is evidence that at least some of this variation may also result from the natural selection brought about by various medical conditions. In a smallpox epidemic in Bihar province, India, researchers found that those who died were more often of blood group A, while survivors were more often of blood group B. In similar fashion, cholera selects against blood group O and favors blood group B. (Note that these studies demonstrated a difference in fitness, but did not explain the mechanism.) Other studies have shown statistical correlation of various blood types with other diseases: blood group O is correlated with an increased risk of duodenal ulcers and ovarian cancers, and blood group A with a slightly increased risk of stomach cancer. Associations of particular blood groups with cancers of the duodenum and the colon have also been postulated. Such statistical associations do not necessarily indicatea cause-and-effect relationship between the associated factors.Fatal diseases are among the most striking agents of natural selection, but there are many other selective forces. We examine some of these other forces of natural selection in the next section.1 How is an average life expectancy measured? Why is the average life expectancy of a population more affected by the deaths of children (e.g., from malaria) than by the deaths of elderly people?THOUGHT QUESTIONS2 All heterozygous carriers of the allele for G6PD deficiency are female. What does this tell you about the location of the G6PD gene? (You may need to review Chapter 3 to answer this question.)Natural Selection by Physical Factors Causes More Population VariationThere are other agents of natural selection in addition to diseases. Among them are climatic factors such as temperature or sunlight, as well as climatic variation that makes food more scarce at some times of year or from one year to another. Like the genetically based traits that confer protection against disease, other genetic variation between populations has arisen in response to these other selective factors. In this section we look at some of these other factors and how they have selected in different geographic regions for differences in the genetically regulated aspects of physiology and of body shape and size.Human variation in physiology and physiqueDuring part of the Korean War (1950–1953), American soldiers were exposed to the fierce, frigid conditions of the Manchurian winter. Many soldiers were treated for frostbite. Most of the Euro-American (Caucasian) soldiers responded well to the medical treatment that was given, but a disproportionate number of African American soldiers did not and many of them lost fingers and toes as a result. Disturbed by these findings, the U.S. Army ordered tests on resistance to environmental extremes in soldiers of different racial backgrounds.In one series of tests, army recruits were required to perform strenuous tasks (such as chopping wood) under a variety of climatic conditions. In a hot, humid climate, the African American soldiers were able to continue working the longest and performed the best as a group; Asian American and Native American soldiers performed nearly as well as the African Americans, and Euro-American recruits lost excessive fluids through sweating and became easily fatigued and dehydrated. Under dry, desert conditions, the Asian American and Native American soldiers did best, the African Americans were second best, and again the Euro-American soldiers became dehydrated. Under extremes of cold, it was the Euro-American soldiers who did best, followed closely by the Native American and Asian American soldiers; the African Americans shivered the most and some became too cold to continue. These tests demonstrated definite differences between groups in bodily resistance to physiological stress under a variety of environmental extremes. The significance of these differences was enhanced by the fact that, in other respects, the recruits represented a fairly homogeneous population: 18- to 25-year-old males who had all been screened by the army as being physically fit and free from disease and who had passed the same army physical and mental exams.Other physiologists outside the Army conducted tests in which adult male volunteers immersed their arms in ice water almost to the shoulders. African Americans in general shivered the most and suffered the most rapid loss of body heat, as measured by a decline in body temperature. Euro-Americans and Asian Americans lasted longer without shivering, but they, too, eventually suffered loss of body heat. Only the Inuit (Eskimo) volunteers were able to keep their arms immersed indefinitely without any discomfort and without shivering. Subsequent studies that replicated these results made the additional finding that diet is also a factor: Inuit volunteers who ate high-protein, high-fat diets (traditional for the Inuit) did far better than other Inuit who had become acculturated to American dietary habits. It would be a mistake, however, to extrapolate findings from studies such as these beyond the groups used for the tests (adult males in good health) without further investigation. Many traits vary with age or sex or both.Bergmann’s rule. Genetically based differences in physiology that correlate with climate are the basis for a number of ecogeographic rules. Adaptations can also work indirectly, through variables such as body physique. Biologists have long noticed certain general patterns of geographic variation among mammals and birds. In one such pattern, called Bergmann’s rule, body sizes tend to be larger in cold parts of the rangeand smaller in warm parts. This can be explained by the relationship of body size to mechanisms of heat generation and heat loss. For example, an animal twice as long in all directions as another animal has eight times the volume of muscle tissue generating heat (2 ¥ 2 ¥ 2 = 8) as the smaller animal but only four times the surface area over which heat is lost (2 ¥ 2 = 4). Thus, the larger animal is twice as efficient as the smaller (8/4 = 2) in conserving heat under cold conditions. A survey of human variation confirms that the largest average body masses are found among people living in cold places (like Siberia), while most tropical peoples within all racial groups are of small body mass, even when their limbs are long. These relationships of body size to climate result from natural selection acting on genetic variation within populations over long periods. It does not mean that a person of a certain genotype will grow larger if they move to a cold climate.Allen’s rule. Another broad, general phenotypic pattern in most geographically variable species of mammals and birds is Allen’s rule: protruding parts like arms, legs, ears, and tails are longer and thinner in the warm parts of the range and shorter and thicker in cold regions. This rule is usually explained as an adaptation that conserves heat in cold places by reducing surface area and dissipates heat more effectively in warm places by increasing surface area. Human populations generally follow this rule: Inuit people have shorter, thicker limbs, while most tropical Africans have longer, thinner limbs (Figure 7.12). There are exceptions, however: a number of forest-dwelling populations along the Equator are much smaller than Allen’s rule would predict, although they are usually thin-legged. Also, the tallest (Tutsi) and shortest (Mbuti) people on Earth live near one another in the Democratic Republic of Congo (formerly called Zaire), showing that climate is not the only instrument of natural selection influencing limb length or overall height within populations.Diabetes and thrifty genes. Diabetes, a potentially life-threatening illness in many populations, may be an indirect result of one or more of the so-called ‘thrifty genes’ that protected certain people from starvation in past centuries. Ancestral Polynesians, for example, endured uncertain journeys over vast stretches of Pacific Ocean waters. Uncertain food supplies during such voyages selected for people who could withstand longer and longer periods of starvation and still remain active. The postulated ‘thrifty genes’ may have caused excess food, when it was available, to be converted into body fat that could be used for energy in times of famine. The result was a population that was stocky in build and resistant to starvation in periods when food supplies were low but that was also more susceptible to diabetes under modern conditions, when physical exhaustion is rare and food is always available. Diabetics fed on ‘ordinary’ diets have excess sugar in their blood, much of which is converted to fat and stored. Although diabetes is itself an unhealthy condition, the storage of fat may have been, under conditions like those described for the early Polynesians, an adaptive trait. Perhaps diabetes is an unfortunate modern consequence of having one orFigure 7.12Bergmann’s and Allen’s rules illustrated by comparisons between arctic and tropical body forms. more alleles originally selected for their ability to convert sugar to body fat.arctic body proportions (Inuit)hot climate body proportions (Sudanese)A similar history of selection for ‘thrifty genes’ (not necessarily the same ones) might also explain the late twentieth-century upsurge of diabetes in certain Native American populations, notably the Navajo and Pima of the southwestern United States. The risks that selected for ‘thrifty genes’ in the past were more significant in barren environments than in places in which the food supply was more assured. However, the commercial introduction of sugar-rich foods and a change from an active to a sedentary lifestyle have both raised the risks of diabetes, which are higher for sedentary people eating carbohydrate-rich diets. Because of these environmental changes, the genes that were once advantageous have in some cases turned into a liability, putting people of these genotypes at greater risk of diabetes. The Navajo and Pima have discovered that a return to frequent long-distance foot racing (a traditional activity they had nearly abandoned) has kept their populations healthier and has significantly lowered the incidence of diabetes in the runners. Not enough time has yet elapsed for the allele frequencies of the ‘thrifty genes’ to have again changed in this population, but the partial return to an earlier lifestyle has changed the environmental stresses and decreased the incidence of diabetes.Natural selection, skin color, and disease resistanceThe skin is the largest organ of the body and a major surface across which the body makes contact with the forces of natural selection in its environment. Human populations vary widely in skin color. Could these differences in skin color be adaptive?Geographic variation in skin color. Skin color is one of the most visible human characteristics, and the one to which Americans have always paid the most attention when identifying race. Long-standing patterns of geographic variation are easier to understand if we ignore the population movements of the years since A.D. 1500 and consider only those populations still living where they did before that time.Europe has for centuries been inhabited by light-skinned peoples, Africa and tropical southern Asia by dark-skinned peoples, and the drier, desert regions of Asia and the Americas by people with reddish or yellowish complexions. What is even more remarkable is that we find geographic variation along the same pattern within most continents, and in fact greater variation within the larger population groups than between such groups. For example, among the group of populations spread continuously from Europe across Western Asia to India, we find the lightest skin colors (also eye and hair colors) in Scandinavia and Scotland, progressively darker average colors (and darker hair) closer to the Mediterranean Sea, further darkening as we move through the Middle East and across Iran to Pakistan and India, and the darkest at the southern tip of India and on the island of Sri Lanka. A similar gradient (a cline) for skin color can be found among Asians, from northern Japan south through China into the Philippines and Indonesia.Why would it be adaptive for people to be light-skinned in Europe but dark in Africa, Sri Lanka, and New Guinea? Notice that there are some very dark-skinned people outside Africa, and they generally have few other physical or genetic characteristics in common with Africans other than their dark skin colors. The natives of Sri Lanka, for example, have very straight hair and blood group frequencies totally different from those of Africa. One clue to this puzzle is that all very dark-skinned peoples have lived for millennia in tropical latitudes.Sunlight as an agent of selection. Tropical regions receive on a yearround basis more direct sunlight than do temperate regions. In fact, the amount of sunlight received at ground level decreases with increases in latitude and corresponds more closely to belts of latitude than to variations in temperature. This is especially true for light in the ultraviolet region of the sun’s spectrum.If we exclude places where few people live, Europe receives the least sunlight of all the inhabited regions of the world. This is first and foremost a function of latitude. Europe includes populated regions of higher latitudes than on any other continent: London and fourteen other European capitals are located north of latitude 50°, while North America and Asia above this latitude contain few large cities and a great deal of sparsely inhabited land. Europe also has a frequent cloud cover that screens out even more of the Sun’s rays. As a result of both high latitude and cloud cover, people in Europe receive much less exposure to ultraviolet light than most other people.That sunlight levels select for body coloration is described by a third ecogeographic rule, Gloger’s rule. While Bergmann’s and Allen’s rules, described earlier, take only temperature into account, Gloger’s rule takes into account sunlight and humidity as well. Under Gloger’s rule, most geographically variable species of birds and mammals have pale-colored or white populations in cold, moist regions, dark-colored or black populations in warm, moist regions, and reddish and yellowish colors in arid regions. We do not know all the reasons for this variation. Camouflage has been suggested as a cause, but vitamin D synthesis also has an important role.Vitamin D is needed for the proper formation of bone. Children who do not receive adequate vitamin D during growth suffer from a condition called rickets, a disease of bone formation that may result in weakness and curvature of the bones (especially those of the legs) and in crippling bone deformities if left untreated. Sunlight is necessary for vitamin D synthesis. Many foods are rich in vitamin D, such as egg yolks and whole milk, but most vitamin D found in foods is in a biologically inactive form. The final step of vitamin D biosynthesis takes place just beneath the skin, with the aid of the ultraviolet rays of natural sunlight. This is why vitamin D is sometimes called the ‘sunshine vitamin.’ To get adequate amounts of vitamin D, a population must have both adequate intake of the vitamin in the diet and adequate exposure to sunlight. European populations have the lightest skin colors (and they get lighter the farther north you go) as an adaptation that allows maximum sunlight penetration into the skin. Europeans also have many cultural adaptations related to vitamin D intake, such as the eating of cheeses and other fat-rich milk products containing vitamin D. Northern Europeans place great value on outdoor activity at all times of the year, including such occasional extremes as nude dashes into the snow after the traditional sauna.In northern Europe, people with dark skins could be at a very high risk of vitamin D deficiency because melanin pigment blocks out a large proportion of the Sun’s ultraviolet rays. Very few dark-skinned peopleFigure 7.13Traditional Inuit fishing. The Inuit get most of their vitamin D from eating whole fish, including the liver.lived in northern Europe even as immigrants. This has changed since World War II, when synthetic vitamin D became widely available. Because this prepared vitamin D is already in its active form, sunlight is no longer needed for its activation. Dark-skinned people can now live and remain healthy in northern latitudes without developing deficiency diseases.At latitudes closer to the Equator, other problems exist. The same wavelengths of ultraviolet that are needed in the final step of vitamin D synthesis are also cancer-causing. Skin cancer (see Chapter 12) is generally a disease of those white-skinned people who are overexposed to the Sun’s direct rays. Recently, it has also been found that ultraviolet radiation from overexposure to the Sun destroys up to half of the body’s store of folate, an important vitamin that protects women against giving birth to children with spina bifida and other neural tube defects. Melanin pigment screens out ultraviolet radiation and thus protects against both cancer and folate deficiency. Populations of all racial groups living closer to the Equator have been selected over the millennia to have darker skins. Those individuals who had lighter skins were less fit in this Equatorial environment; that is, they more often got skin cancer and died earlier, or more often had deformed babies or miscarriages. Melanin pigment absorbs much of the ultraviolet light, protecting dark-skinned people against skin cancer and folate deficiency, while still allowing enough ultraviolet light through for adequate synthesis of Vitamin D.There are no known genes that code specifically for skin color (except that the allele for albinism, present in all human populations, prevents synthesis of all melanin pigment and results in pale white skin). Apart from environmental effects (such as suntanning), there are probably dozens of genes that produce enzymes that influence the synthesis of melanin and other skin pigments—so many that it is difficult to study any one of them apart from the others. Nevertheless, natural selection has favored different levels of pigmentation in different geographic regions.Nutritional sources of vitamin D in the far north. For the reasons given in the preceding sections, populations living in the high latitudes are generally light-skinned and populations that are adapted to living in tropical latitudes are generally dark-skinned. There is one very interesting exception: the Inuit populations of Arctic regions, some-times known as Eskimos. (These people have always called themselves Inuit; the name ‘Eskimo’ was a pejorative name used by their enemies.) The Inuit are not very light-skinned, nor do they expose themselves much to sunlight. Most Inuit people live in places so cold that the exposure of bare skin poses a greater danger than any benefit of ultraviolet rays could overcome, and most Inuit are fully protected by clothing that offers hardly any exposure to the Sun. So how do they get enough vitamin D? The Inuit have discovered their own way of staying healthy. One of the world’s richest sources of vitamin D is fish livers, especially those of cold-water fishes. (Cod liver oil is a very rich source of both A and D vitamins.) Moreover, the vitamin D in fish oils is fully synthesized and needs no sunlight to activate it. So, instead of having pale skins and traditions of exposing their skins to sunlight, the Inuit have traditions of catching cold-water fish (Figure 7.13) and eating them whole, liver and all. These traditions have allowed them to stay healthy in a climate that is too cold and too sunless for most other populations.In all of the above examples, a population that has lived in a particular geographic area for long periods has become adapted to the temperature, humidity, sunlight, and other conditions of their environment. The evidence presented in this chapter and in Chapter 5 suggests that natural selection is largely responsible for these adaptations.1 If people differ in their resistance to extreme cold or heat, does this mean that the difference is genetic? What would you need to know to answer this question?How could an experiment be arranged to test this?THOUGHT QUESTIONS2 Blood type O is statistically associated with duodenal ulcers, one of many such correlations between a blood type and a disease. Does a correlation demonstrate a cause? Does a correlation imply a mechanism of some kind? Does a correlation suggest new hypotheses? How can scientists learn more about whether there is a causal connection between the blood type and the disease?Concluding RemarksThroughout the history of biology, scientists have developed various ways of describing groups of people. Some of these groupings have been known as races. Some concepts of race have attempted to find biological explanations for the racial groupings already established by various societies. Morphological concepts of race divided humans on the basis of their physical appearance. Biologists and anthropologists of the past gathered descriptive data about the physical characteristics of different populations and assumed that each group was distinct and unchanging. More recently, biologists have abandoned these concepts, in part because of the racism that has flowed from them, but also because these ideas no longer fit the data that we now have. The population genetics theory of human variation views human populations as varying continuously, with no group being uniquely different from any other. Biological differences among human populations are products of evolution. Like any other species, humans can evolve only when genetic variation is present in a population. When a population encounters some agent of natural selection, such as disease or climate, people with certain genotypes survive in greater numbers and leave more offspring than those with other genotypes. Over long periods, this process results in the adaptation of a population to its environment, with allele frequencies differing from one population to the next. This evolution continues today, although the increased mobility of people and technological alterations of the environment are slowly making populations less distinct than in past centuries. Populations vary in the frequencies of traits; they do not carry any unique traits. There is no biological phenotype, genotype, or DNA sequence that can assign an individual to a race or to a population. Although our biological concepts about race and other human variation have changed over time, racism will continue to exist if one group of people is held to be more valuable than another.Chapter SummaryHuman populations vary geographically. Phenotypic and genotypic variation within populations usually exceeds variation between them.Phenotypic variation within a population can be either continuous or discontinuous. Continuously variable traits, in which all intermediate values are possible, can be described in terms of average values for each population. Discontinuously variable traits, such as those that are either present or absent, can be described in terms of phenotypic frequencies or allele frequencies.Differences among populations have historically been described in terms of culturally defined or morphological races.Population genetics allows us to describe groups of populations that differ from one another by certain characteristic allele frequencies.Most allele frequencies vary gradually and continuously among populations, without abrupt boundaries. Continuous variation from one population to another is best described in terms of geographic gradients, also called clines. Clines can be plotted on maps for average values of continuously variable traits such as height, or for population frequencies of discontinuously variable traits such as particular blood groups or alleles or DNA sequences.When more than one allele of a gene persists in a population this is called a polymorphism.The Hardy–Weinberg equilibrium describes the conditions under which allele frequencies remain constant in a population.Populations that were at one time small may have allele frequencies that have been shaped in part by genetic drift.Aside from genetic drift, most geographic variation among human populations has resulted from natural selection producing adaptation of the population to the environment.Disease is an important force of natural selection. Malaria, a widespread parasitic infection, has selected in different regions for high frequencies of alleles associated with sickle-cell anemia, thalassemia, and G6PD deficiency, all of which protect heterozygous individuals against malaria. Malaria and other diseases result in balanced polymorphism whenever the heterozygous genotype enjoys maximum fitness.Temperature selects for geographic variation in the alleles influencing body size and body shape.Ultraviolet light at different latitudes selects for geographic variation in the population frequencies of alleles influencing skin color. Alleles producing pale skin are selectively favored at high latitudes as an adaptation to absorb more ultraviolet light and prevent vitamin D deficiency. Alleles producing dark skin are favored near the Equator as a protection against skin cancer from too much ultraviolet exposure.CONNECTIONS TO OTHER CHAPTERSChapter 1 Every study of human variation is conducted in a cultural context.Chapter 1 Studies of human variation have ethical implications, including those arising from inappropriate use of the results.Chapter 3 Many human variations have a genetic basis; such alleles arose ultimately from mutations.Chapter 5 Human population variations reflect evolutionary processes, including mutation, natural selection, and genetic drift, all of which continue to work in modern populations.Chapter 9 Nearly all human populations are growing, and some are growing much faster than others. Population growth and migrations change various allele frequencies.Chapter 10 Different populations sometimes have different ways of meeting their nutritional requirements.Chapter 12 Some types of cancer are more frequent in some human populations and less frequent in others.Chapter 18 Human variation is an example of biodiversity at the population level.Chapter 19 Because of damage to Earth’s ozone layer, people are being exposed to increased ultraviolet radiation, which may select over time for a shift in allele frequencies leading to a darkening of skin pigmentation in human populations.PRACTICE QUESTIONSHow many different genotypes can code for the blood group B phenotype? What are they? Are they heterozygous or homozygous?How many different genotypes can code for the blood group AB phenotype? What are they? Are they heterozygous or homozygous?How many different genotypes can code for the blood group O phenotype? What are they? Are they heterozygous or homozygous?How many different genotypes can code for the Rh– phenotype? Are they heterozygous or homozygous?How many different genotypes can code for the Rh+ phenotype? Are they heterozygous or homozygous?If the allele frequency of HbS in a population is 0.1, how many people in that population will be heterozygous HbAHbS? (Review the Hardy–Weinberg equation.)How many different host species does the Plasmodium parasite need to complete its life cycle?Why do people who are heterozygous for sickle-cell anemia have less severe anemia than people who are homozygous HbSHbS ?How does the bottleneck effect alter the allele frequencies of a population?What is a balanced polymorphism? Give an example.IssuesWhat is sociobiology? How is it different from sociology?Why does sociobiology have so many critics?Who is objecting, and what are they objecting to?Is most behavior learned or inherited?What are the differences between instincts and other innate behaviors?How do learned behaviors relate to evolutionary change?To what extent can social behavior be modified?Why do the sexes behave differently in so many species?How different are humans from other species in social behavior? To what extent can findings in other species be extrapolated to humans?Evolutionary change (variation, natural selection, nonrandom mating, specializationand adaptation, human evolution)Population ecology (populations, regulation of population size)Learning and instinct (interaction of genotype and environment)Reproduction (asexual reproduction, sexual reproduction, mating systems, sexual dimorphism, reproductive strategies)Behavior (social behavior, communication, courtship and mating)Chapter OutlineSociobiology Deals With Social BehaviorLearned and inherited behavior The paradigm of sociobiology Research methods in sociobiology InstinctsSocial Organization Is AdaptiveAdvantages and disadvantages of social groupsSimple forms of social organization Altruism: an evolutionary puzzle The evolution of eusocialityReproductive Strategies Can Alter FitnessAsexual versus sexual reproduction Differences between the sexes Mating systemsPrimate Sociobiology Presents Added ComplexitiesPrimate social behavior and its development Reproductive strategies among primates Some examples of human behaviors8245Sociobiologyehavior that influences the behavior of other individuals of the same species is called social behavior. Examples of social behavior inanimals include cooperative feeding, cooperative defense, aggression within the species, courtship, mating, and various forms of parental care. People also practice many forms of social behavior: nurturing their young, helping their neighbors, defending their possessions, and providing both material help and emotional support to their loved ones and to others. The population crisis discussed in Chapter 9 is a direct result of reproductive behavior. Some types of social behavior are often termed ‘antisocial’ behavior and result in problems for society. Examples include violence, crime, racist acts, sexist acts, and child abuse and neglect, all of which are social behaviors because they affect the behavior of other individuals.Sociobiology is the comparative study of social behaviors and social groupings among different species. The study of social behaviors in complex human societies is a separate discipline called sociology.Can behaviors that cause problems be changed easily? Can beneficial behaviors (however defined or recognized) be substituted for destructive behaviors? Is most behavior rigid and unchangeable, or plastic and easily molded? Are we governed more strongly by our genetic background (nature) or by our upbringing (nurture)? The debate is very old. In Shakespeare’s Tempest (4:1), Caliban is described as “a born devil on whose nature / Nurture can never stick.” If human behavior were strongly determined by genes, then cultural influences, including education and training, would have only limited power to bring about changes in human behavior. Social reformers of all kinds usually support the opposite viewpoint, that human behavior can be modified almost at will, subject to few if any restrictions. Debates about alcoholism or homosexuality are often unproductive because some people assume that these are behaviors that could easily and voluntarily be changed, while others assume that these are permanent and deeply rooted in biological differences that may or may not be genetic. Differences in behavior between the sexes are likewise seen by some researchers as genetically constrained and by others as culturally controlled and easily changeable.Although the most heated discussions arise from attempts to apply sociobiology to humans, sociobiology is a broad field of study and humans are but a single species. Most research in sociobiology focuses on nonhumans. Altruism, for example, poses a major research question in the sociobiology of all species. Among other broad-spectrum issues within sociobiology are the advantages of sociality itself, the kind of social organization found in each species, and the manner in which it evolved.Another issue is that of social relations between the sexes of each species, including the concept of reproductive strategies; in this chapter we show that parental care, infanticide, adultery, and altruism can all be viewed as components of reproductive strategies. The evolution of these strategies is an important field of investigation for sociobiology. In this chapter we examine the sociobiology paradigm and some of the major issues within the paradigm.246Sociobiology Deals With Social BehaviorSociobiology means different things to different people. To scientists working in sociobiology, it is a field of study that deals with social behavior and its evolution. Sociobiologists usually explain behaviors in evolutionary terms. Although sociobiologists are more interested in the inherited components of behavior, they all acknowledge that much of behavior can also be modified by learning. They also acknowledge that natural selection can act only on those components of behavior that are inherited. One of the important research goals of sociobiology has therefore become the investigation of the relative importance of learned and inherited influences on particular behaviors. Sociobiology also has a number of critics who challenge the emphasis on inherited behavior patterns. These critics prefer to emphasize learning, including cultural learning in humans, as a strong influence on behavior. We will examine both viewpoints.Learned and inherited behaviorMany behavioral patterns may be strongly influenced by experience in dealing with the environment, i.e., by learning. Nearly every behavior that has been carefully investigated also has some genetic component. Learned behavior may increase fitness, but only the genetic components (or predispositions) underlying the behavior can be influenced by natural selection (see Chapter 5). Natural selection can operate on the capacity for learning particular kinds of things, such as how to find one’s way through the maze of one’s surroundings. The character favored by selection in such cases is not the behavior itself, but rather the capacity to learn the behavior.This is true of the ability to run through mazes, one of the most often studied types of learned behavior. Rats were tested for their ability to learn certain mazes, and the number of training sessions that it took the rats to learn the mazes was recorded. Their littermates, who were never tested themselves, were then selectively bred for several generations. Breeding the littermates of fast maze-learners resulted in a strain in which the average number of training sessions needed was low, while a strain of slow learners was bred from the littermates of individuals who needed more repetitions. The use of littermates in this experiment eliminated learning experience or other influences as determinants of the differences between the two selected strains. Notice that the behavior was not fully determined by inheritance; it still had to be learned. This behavioral trait is determined by many genes and environmental influences acting together. The difference between the two strains resulted from the buildup of gene combinations, which was only possible because some portion of the variation between groups was heritable.Furthermore, to say that variation between groups is heritable does not mean that the behavior is inherited as a fixed and unchangeable trait. There are extremely few behaviors in any species (and none at all in humans) that are not subject to modification through learning. For example, nobody learns to play basketball like Michael Jordan or to play the cello like Yo Yo Ma without years of practice. Nobody can become even a mediocre basketball or cello player without lots of practice—a period of learning. However, some innate talent and ability are surelyFigure 8.1Learned versus innate behavior patterns.needed, or else any of us would be able to become a great basketball star or a world-renowned cellist simply by practicing enough.Thus, it is important to emphasize that the oft-posed question of learned versus inherited behavior is a false dichotomy. Every learned behavior is based in part on some inherited capacity to learn, which may include the capacity to learn certain kinds of behaviors and not others, to respond to some stimuli and not others, to learn up to a certain level of complexity, and so on. Similarly, most behavior patterns with an inherited component can be modified to some extent by learning. These observations give rise to the testable hypothesis that nearly every behavior pattern is at least partly learned and at least partly inherited. Behaviors that do not require learning are called innate, and innate behaviors are assumed to have an inherited component. No behavior is 100% learned, and few are 100% inherited in any species (Figure 8.1). The methods used to distinguish between learned and innate components of behavior are described later in this chapter.The paradigm of sociobiologySociobiology, the study of social behavior among different species, uses a scientific paradigm of the kind described in Chapter 1: one or moreNursing and suckling behaviors have strong innate components in most mammals(but this doesn’t prevent bottle-feeding of many human infants).Novel behaviors can be learned by many species.Most forms of behavior show both learned and inherited components. Robins and many other birds innately peck at certain stimuli and thereby gain learning experiences about how to hunt more effectively and how to distinguish food objects from other objects. theories, plus a set of value-laden assumptions, a vocabulary, and a methodological approach (Box 8.1). The formulation of sociobiology as a paradigm dates from the publication of the book Sociobiology: the New Synthesis, by the American evolutionary biologist Edward O. Wilson (1975). Many of the ideas of this paradigm can be traced to Charles Darwin’s writings. What was new in 1975 was the way in which these ideas were put together to form the paradigm.If people outside the paradigm had viewed sociobiology as no more than the study of social behavior, few objections would have been raised to it. However, sociobiology was frequently criticized for its focus on inherited behavior. As the many critics of sociobiology have emphasized, much of behavior is learned, and nearly all behavior can be modified by learning, particularly in mammals. Also, human behavior is strongly influenced by both language and culture, so many scientists who are otherwise sympathetic to sociobiology have cautioned against extrapolating sociobiological findings from other animals to humans.Some nonscience critics of sociobiology are fearful of genetic deter-minism, the assertion that our individual characteristics are determined before birth and cannot be changed. As we discussed in Chapter 7, genetic determinism is feared because throughout history people in power have sought to control other people (other social classes, other races, and women) by teaching that existing inequalities were ‘natural,’ based on innate and unchangeable differences. Also, many people fear that the mere claim that a behavior is innate will discourage people from trying to change that behavior through education or similar means. The claim that behavior is innate can be particularly threatening to social reformers who pin their hopes for the future on the ability of people to modify their behavior.Among biologists, those who believe in genetic determinism are decidedly in the minority. Most biologists, especially those who study animal behavior, are impressed with the degree to which behavior can change in response to environmental circumstances, including the behavior of other individuals. There are genetic constraints on what can and cannot be learned, but, within these limits, behavior is remarkably changeable (or ‘plastic’) in most animal species. No behavior is fully ‘determined’ either by genetics or by environment—almost every behavior is influenced by both of these factors throughout the lifetime of the individual.We now examine the research methods used by sociobiologists.Research methods in sociobiologyNo behavior can be analyzed by any method until it has been adequately described. Sociobiology therefore includes a great many observational field studies of animals. How does one distinguish between the learned and innate components of a particular behavior? Sociobiologists use the following methods to investigate these components.Rearing animals in isolation. A classic type of experiment is to raise an animal in isolation, in a soundproof room with bare walls and minimal opportunities for learning, including no opportunity to learn behavior from others. Behavior that the animal exhibits under these conditions is assumed to be largely innate. Experiments of this sort cannot ethically be done on humans.BOX 8.1 The Sociobiology ParadigmResearch activity in science is often organized around paradigms (see Chapter 1). Here, in brief outline form, are some of the major points of the sociobiology paradigm:Behavior is interesting to observe and to study. (This is a value judgment; people who do not share it will never be attracted to the paradigm.)Much of the interesting behavior influences the behavior of other individuals, and is called ‘social.’ (This is a definition with an implied value judgment that people within the paradigm are expected to share.)Social behavior has evolved and continues to evolve. (This is a central theory whose rejection would bring down the entire paradigm.)The evolution of social behavior takes place by natural selection, along the lines outlined by Darwin: variations occur, and the variations that increase fitness persist more often than those that do not. (This is again a theory; it includes theoretical concepts such as ‘fitness’ and ‘variation.’)Behavior is often modified by individual experience (‘learning’). However, this learning takes place within limits set by the biology of the organism: the eyes limit what can be seen (likewise with other sense organs); the muscles and skeleton limit the possible responses; the structure of the brain limits the learning capacity, and so on. There are also many preexisting predispositions to respond to certain types of stimuli, to react in certain ways, and so on. These predispositions may have been learned at an earlier time, but at least some of them precede any learning and may be called ‘innate.’ (This is a central tenet of the paradigm, forming the basis for its further research.)In the evolution of behavior, learned modifications are not directly inherited. Learned behaviors can contribute to fitness, but cannotbe inherited. Only the innate predispositions and their biological underpinnings can be inherited, and only these inherited components can evolve. Natural selection can only work on the inherited aspects of behavior. (These ideas follow in part from the ways in which ‘learned’ and ‘innate’ are defined, and in part from the findings of evolutionary theory.)It is therefore important to distinguish the learned and innate components of behavior, and to focus attention on the latter. This is a value judgment about the aims of research within the paradigm. It does not mean that learned behaviors are unimportant; it just means that sociobiologists would rather identify what is learned so that they can ignore it and spend the rest of their time studying the innate components. It is this preference for studying the innate components of behavior that makes the sociobiology paradigm so controversial; most critics of sociobiology have the opposite preference.We can use modified Darwinian methods of investigation to study those components of behavior that evolve. One method is to measure variations in fitness by observing many individuals and studying the number of viable offspring successfully reared by each. Another method is to study the results of past evolution by comparing social behaviors among different populations or different species. (These are the basic research methods.)Before comparisons can be made, however, there must first be an often lengthy period of observation and description. However, we realize that the presence of observers might modify the behavior that we wish to study. Because we are interested in behavior under ‘natural conditions,’ it follows that we should conduct most observations at a distance and interfere as little as possible. (These are more research methods.)Rearing animals under different conditions. If the behavior is performed in the same way by animals or humans reared under strikingly different circumstances, then the behavior is largely innate. If, in contrast, the behavior varies according to the circumstances of rearing, then the variation can be attributed to environmental influences, although this does not rule out inherited influences, which may also be present. Cross-cultural studies are used to compare the behaviors of people raised in different societies or under different customs; innate behaviors are expected to be constant across various cultures, while learned behavior patterns are expected to vary.Studying behavior in different genetic strains. If different strains or breeds of a species differ behaviorally in a consistent and characteristic way, then a strong inherited component exists. (This does not rule out learned components, which might also be present.)Conducting adoption studies. If two populations differ in a particular behavior, it may be useful to study individuals from one group who are adopted early in life and raised by the other group. Under these conditions, behavior consistently resembling the population of birth demonstrates an inherited influence, while behavior resembling the population of rearing demonstrates a learned influence. Mixed or inconsistent results may indicate that both influences are present.Conducting twin studies. If a trait is under strong genetic control, then identical twins should usually both exhibit the trait whenever either one does, while fraternal twins more often exhibit differences. Twin studies in humans are frequently criticized because the effects of learning cannot easily be separated from those of inheritance unless the twins are reared separately in families randomly chosen, conditions that are rarely even approximated. Some studies compare identical twins reared together to those reared apart, an experimental design that attempts to get around some of these difficulties.InstinctsA subset of innate behaviors are called instincts. Instincts differ from other innate behaviors in being complex behavior patterns that are under strong genetic control. The classical test for whether a particular behavior is an instinct is whether the behavior appears at the appropriate time of life in an animal reared in isolation since birth or hatching. For example, if a songbird reared in a soundproof room sings the song of its species and sex upon reaching maturity, then the song is considered to be instinctive. By this test, many behaviors that have been studied in fishes, birds, and many invertebrates (including insects) have been shown to be largely instinctive. Behaviors related to courtship and mating usually have strong instinctive components in most species. Other behavior patterns that are frequently instinctive include automatic ‘escape’ behavior, nest-building behavior, orb-weaving in spiders, and various threat gestures. When instinctive behavior leaves a lasting product, such as a nest or a spider’s web, these products are often so distinctive that they can be used to identify the species that created them.Mammals generally rely more on learned behavior than on instinct. Among primates especially, many behaviors that are instinctive in other species have strong learned components. These behaviors may vary greatly among human societies.Advantages of instincts. Short-lived animals rely heavily on instincts. For example, mayflies (insects of the order Ephemeroptera) have an adult life span of less than 24 hours. During this brief period they do not feed but have just enough time to find a mate, copulate, lay their eggs, and die. There is no time for learning to take place, nor is there any time for mistakes. The mayflies that accomplish their mission successfully are those that can perform their behavior correctly on the first try; they will probably never get a second chance. Selection over millions of years has therefore produced a series of adult behaviors that are instinctive and automatic, allowing no room for diversity or innovation. This is typical of instincts generally: behavior is instinctive in contexts in which uniformity and automatic response are adaptive and where innovation and diversity might be maladaptive. A greater complexity of behavior is possible with a simpler brain if the behavior is instinctive; learned behavior of equal complexity requires a more elaborate nervous system and also a long learning period during which many mistakes are made.Mating behavior. Mating behavior includes both courtship (attracting a mate and becoming accepted as a mate) and the actual release or transfer of gametes. Mating behavior has a strong instinctive component in nearly all species, except in higher primates. Scientists can demonstrate the instinctive component of most forms of mating behavior by raising individuals in isolation until they are sexually mature, then testing them to see whether they can perform the behavior typical of their species.Natural selection favors uniformity in mating behavior rather than diversity. Such unvarying behavior (called stereotyped behavior) is used for mate location and recognition in many species. The behavior that evolved in each species matches the type of signal that each is able to sense, so that visual mating signals are used by species with good vision, chemical signals by species with good chemical reception, and sounds by species with good sound discrimination. Many species of birds, frogs, and insects use sounds as mating signals, and the noncalling sex (usually female) responds only to mating calls of the proper pitch, duration, and pattern of repetition. Both the mating signals and the behavioral response to them are instinctive. Members of each sex know exactly what to listen for in the other sex and usually avoid nonconformers who deviate from the instinctive pattern. Sexual selection thus penalizes the nonconformers, who generally fail to mate and therefore leave no offspring. The flashing patterns of fireflies, though visual, are sexually selected in the same way. Because of sexual selection, mating calls or visual displays are precisely controlled within a narrow range for eachspecies. Closely related species often differ in their mating calls andcourtship patterns. Differences in mating calls and other courtship displays often serve as reproductive isolating mechanisms that prevent interbreeding between species (see Chapter 5).Male birds of many species display conspicuously colored parts during courtship. Mating rituals that include beautiful, ornate displaysevolve as a consequence of sexual selection in those species where the discriminating sex (the one doing the choosing) consistently prefers the most conspicuous displays. Peacocks, lyre-birds, and birds-of-paradise are renowned for their beautiful and ornate male plumage (Figure 8.2). Male birds of species with less conspicuous plumage may concentrate instead on building an elaborate nest. The South Pacific bowerbirds build their nests within a large framework (a bower) that also serves as a place of mating. A few species evenbuild an ‘avenue’ lined with colorful stones leading to the entrance of the bower. Generally, bowerbird species with ornate plumage do not build elaborate bowers, and the species that build impressive bowers do not have elaborate plumage.Territorial behavior. In many species, one or both sexes may show territorial behavior by defending a territory, either throughout the year or only during the mating season. The defense of a territory against intruders of the same species is common in many animalspecies. In some species, only males are territorial. Territorial behavior spaces individuals apart and encourages the losers to strike out in search of new territory, thus extending the range of the species wherever possible. Each territory must have sufficient food resources for a mating couple and their offspring, places for hiding and refuge, and at least one suitable nest site. Males without any territory are usually unable to attract mates and thus leave no offspring in that particular season. The specific boundaries of a territory and one’s status as a territory holder or a trespasser are learned, but the general tendency to establish territories is instinctive in certain species (or sexes or seasons).Territorial species may use gestures to threaten territorial rivals. Mammals who establish territories may mark their territory with their own scent. The intimidation of rivals by gestures or by the presence of odors serves to space individuals apart without causing injury or loss of life. Such ritualized forms of territorial defense are much more common than any form of fighting in which injuries are likely.Nesting behavior. The choice of a nesting site may be an important part of territorial behavior. In some bird species, the male builds the nest and then offers it to the female as part of the mating ritual. In other species, male and female may cooperate in building the nest together as part of the mating ritual. Females may incubate the eggs alone, but males may provide other forms of assistance by bringing food or by defending the area against predators. In other species, the males and females take turns in guarding the nest and sitting on the eggs. Feeding the hatchlings may similarly be either a solitary or a shared task.The behaviors just described are performed by individuals. Behaviors can also be performed by groups of organisms, a subject that we take up in the next section.Figure 8.2An example of a conspicuous mating display in a peacock. Females of this species prefer males with the most conspicuous displays.THOUGHT QUESTIONSDoes ‘antisocial’ behavior (such as assaulting others and causing them injury) fit the definition of social behavior? Do you think the definition should be modified? In what way?Is sociobiology a subject area with room for many viewpoints, or is it a single viewpoint that enshrines both genetic determinism and sexism? Can sociobiology be studied without the assumptions of genetic determinism?Can the methods used for gathering or analyzing data in sociobiology be the same for different species? To what extent do size (small versus large animals) or habitat (above ground, underground, underwater, in trees, etc.) require differences in field methods? What special problems in methodology arise when humans are being studied? Can the methods used for other species be applied to humans?Social Organization Is AdaptiveVery few animal species consist of solitary individuals that spend all their time alone. Even in species whose members are solitary much of the time, individuals must come together for sexual reproduction. Most species, however, are far more social than this, and species that form social groups greatly outnumber those that consist primarily of solitary individuals. Social groups vary greatly in both size and cohesiveness. Simple pairs and family groups have only a few individuals. Larger social groupings include antelope herds, baboon troops, and fish schools, all of which may include up to a few hundred members. Still larger are the colonies of social insects, which may include many thousands or in some cases millions of individuals. Some social groups are loosely organized, with individuals staying together but seldom interacting, while others are organized into social hierarchies within which interactions are complex, as they are among humans and social insects.Advantages and disadvantages of social groupsThere are clear disadvantages to living in a social group. Chief among these is the competition for food and other resources (mates, hiding places, nesting sites), and this competition is made more intense by the fact that members of the same species generally have exactly the same ecological requirements (they seek the same foods, nesting sites, etc.). In those cases where food comes in portions small enough to be monopolized by a single individual, social groups are often small or non-existent. Social groupings also foster the spread of parasites and infectious diseases, and they may make the group easier for a predator to spot. Species that rely on camouflage avoid forming densely clustered social groups.Despite these disadvantages, we find that species in which there are social groups far outnumber the species formed by solitary individuals. Clearly, there must be some great advantages for social groups.Some advantages of social grouping are related to the obtaining of food. A large group of individuals searching for food together has a higherprobability of finding it than a single individual. If food tends to be discovered in quantities much greater than a single individual needs, selection favors the formation of social groups.Finding a mate is made easier if there are social groups. Indeed, many species that are solitary throughout most of the year come together on occasion, often during a particular season, and form social groups and mate. The risk of inbreeding increases if social groups are small and remain closed to the introduction of new genes; this risk is usually minimized by mechanisms for the exchange of genes or of individuals between populations.Other advantages of social grouping relate to defense against predation. Social groups can often defend themselves more effectively than individuals can. Musk oxen, for example, respond to threats by standing close together with individuals facing outward in different directions (Figure 8.3). Even in species that do not practise group defense, members of a group may warn one another by giving alarm signals, or simply by fleeing as soon as a predator is spotted. Thus, belonging to a group gives all group members the advantage of greater (and earlier) alertness against predator attacks. For this reason, large but loosely organized flocks, schools, or herds are common amongbirds, fishes, and ungulates (hoofed mammals such as wildebeest and zebra) (Figure 8.4). Other advantages to group membership arise from the sharing of risks: a predator attacking the entire herd may capture one of its members at most, while the rest escape, so that each individual in a herd of 500 is exposed to only 1/500 of the risk of capture faced by a solitary individual. Actually, the risk may be even smaller because predators can more easily capture solitary individuals. Most herd animals taken by predators are individuals that have strayed from the herd.Simple forms of social organizationSocial organization refers to the ways in which social groupings are structured. The fact that social organization sometimes varies among closely related species suggests that social organization evolves. Studies on the inheritance of social status (dominance) within organized social groups point to a complex interplay of learned and inherited behavioral components in the establishment of social organization.Groups without dominant individuals. Perhaps the simplest form of social organization is shown by brittle stars (see Figure 6.17, p. 192), marine organisms distantly related to sea stars. On encountering one another, brittle stars tend to stay together in clumps, even though there is no evidence of any more complex interaction.The schooling behavior of fish is another very simple form of social organization. There are hydrodynamic advantages to schooling—swimming is made slightly easier by certain changes in water pressure caused by the swimming of the other fish—but these effects are small. The major advantage to schooling behavior may be that the fish hide behind oneFigure 8.3Musk oxen in a defensive formation. When musk oxen stand close together and face in different directions, no predator can surprise them.Figure 8.4Social groups in various species.another in such a way that most escape predators. Most fish school closer together when a predator is nearby (see Figure 8.4). When attacked, schools of fish or flocks of birds tend to scatter in every direction, a reaction that confuses many predators and that gives the individuals a chance to escape.The size of social groups can vary greatly, often in response to ecological factors. For instance, the weaver birds live in many parts of Africa and Asia. In humid, forested regions, most weaver birds nest in pairs and feed on insects, while those species inhabiting grasslands and other drier habitats build large communal nests and eat a diet rich in seeds.Groups with dominant individuals. One form of social organization is called a linear dominance hierarchy or ‘pecking order.’ Such hierarchies are found among domestic fowl and certain other captive animals (Figure 8.5). The top-ranked individual, usually a strong male, can successfully bully or threaten all the other individuals in the group, literally pecking at them in the case of birds. The second-ranked individual can intimidate all others except the top-ranked individual. The third-ranked individual can intimidate all except the first two, and so on. Occasionally, two closely ranked individuals may be tied for status, so that neither can dominate the other. For the most part, however, this type of organization results in the biggest bully getting whatever he wants, the second biggestPelicans Minnows schooling in the presence of predatorsWildebeest on the plains of Africa Gannets on the coast of Quebecgetting whatever he wants as long as he steers clear of the top-ranked individual, and so on. Some feminist critics of sociobiology suggest that such male-dominated forms of social organization exist more in the minds of male sociobiologists than in the animals that they study. In at least some studies, pecking orders may reflect the artificial conditions of captivity and confinement.Altruism: an evolutionary puzzleEfforts to solve human social problems such as pollution often call for individuals or corporations to sacrifice their own interests for the common good, a practice called altruism. Altruistic behavior exists in many other species as well. As anexample, consider the ‘broken wing’ display of certain female birds such as nighthawks. When guarding her nest against a predator, a female nighthawk may lead it away from the nest location, distracting its attention by limping or pretending to have a broken wing. Once she has drawn the predator sufficiently far from the nest, she flies away, leaving the predator confused. While protecting her young, she has increased her own danger. In evolutionary biology, altruism is defined asbehavior that decreases the fitness of the performer while it increases the fitness of another individual. In this example, the female bird has decreased her own fitness by putting her life at risk for the sake of her offspring. Remember that fitness is defined as the relative number of fertile offspring produced by an individual (see Chapter 5). Only changes that increase fitness are perpetuated by natural selection.Altruistic behavior poses a problem in evolutionary theory because natural selection might be expected to work against it. How could altruism evolve if it decreases fitness? Various hypotheses have been developed to explain this. In this section we examine several hypotheses that act at different levels of selection.Selection at the species level. One early hypothesis for the evolution of altruism is that it benefits the species as a whole. However, careful examination of this hypothesis shows it to be unsatisfactory. If a species had both altruists and selfish individuals (‘cheaters’), and if some part of this behavioral difference were controlled genetically, then selection would work against the altruists and in favor of the cheaters. Altruism may benefit all recipients of another individual’s altruistic behavior, but the advantage is greater to selfish individuals than to other altruists. Under these conditions, natural selection should favor selfishness and eliminate altruism from the population.Group selection. Another possible explanation for the evolution of altruism was proposed by the British ecologist V.C. Wynne-Edwards. If aFigure 8.5Domestic fowl showing a pecking order. species is subdivided into populations or social groups, then selection among these groups (group selection), may favor one group over another. In particular, a group containing altruists is favored as a group over other groups composed of selfish individuals only.As we explained earlier, the defense of territory prevents excessive population density by spacing individuals apart and limiting population size. Wynne-Edwards describes the losers of territorial disputes as altruists who forgo mating for the benefit of the group as a whole. He argues that the mating of individuals without territories would lead to overpopulation, increased mortality, and a smaller resulting population size. Selection between groups would thus favor altruism. Other biologists who have examined this claim with mathematical models have shown that a loser who cheats (mates anyway) would greatly increase its fitness over one who does not mate, and that cheating behavior would thus be favored over altruism in every territorial species. Similar arguments have been advanced to show that other behaviors that achieve spacing or population control would also not be favored by group selection because cheaters would tend to leave more offspring than altruists.Kin selection. Many biologists dissent from the group-selection hypothesis, seeking instead a simpler explanation based on individual selection. The currently favored explanation of altruism is based on the concept of inclusive fitness, defined as the total fitness of all copies of a particular genotype, including those that exist in relatives. Relatives are listed according to their degree of relationship, symbolized by R. For sexually reproducing organisms with the common types of mating systems, an individual shares half of its genotype (R = ½) with its parents, its children, and, on average, with its brothers or sisters (who share two parents). Also, an individual shares one-fourth of its genotype (R = ¼) with grandchildren, half-siblings (who share one parent only), uncles, aunts, nieces, and nephews. The inclusive fitness of your genotype is the sum total of your individual fitness plus one-half the fitness of your parents, children, and full siblings who share half your genotype, plus one-fourth the fitness of those relatives who share one-fourth of your genotype, plus one-eighth of the fitness of your cousins who share one-eighth of your genotype, and so on. This concept allows us to define kin selection as the increased frequency of a genotype in the next generation on the basis of its inclusive fitness.The conditions under which kin selection favors the evolution ofaltruism were specified by the British sociobiologist William D. Hamilton. Assume that altruistic behavior results in a certain reduction in fitness or ‘cost’ to the altruist, and a corresponding gain in fitness or ‘benefit’ to another individual who shares a fraction of the altruist’s genotype. Hamilton reasoned that natural selection would favor altruism whenever the gain in inclusive fitness to the altruist’s genotype exceeds the cost. If I perform an altruistic act that diminishes my individual fitness by a certain cost but raises my child’s fitness or my sister’s fitness (with whom I share half my genotype) by more than twice that cost, then the net effect on my inclusive fitness is positive. The probability that my genotype will be represented in future generations is increased because the benefit tomy relatives (or to the fraction of my genotype that they share) exceeds the cost, so the net result is an increase in my inclusive fitness.The above explanation, however, gives rise to an interesting prediction: kin selection favors altruism only if close relatives are more likely to benefit from altruistic acts than more distant relatives or nonrelatives. Studies of many species have confirmed this prediction: the beneficiaries of altruism are often close relatives of the altruist, and the frequency of altruistic acts varies in almost direct proportion to the degree of the relationship. In the Florida scrub jay, the offspring of the previous year are not mature enough to mate. Instead, they help the nestlings who are their own brothers and sisters (Figure 8.6). In doing so they contribute to the survival (and thus the fitness) of these near relatives, who share a portion of their own genotype. Ground squirrels emit an alarm call when a predator is spotted. The alarm call decreases the fitness of the caller, but increases inclusive fitness by warning the caller’s kin (see Figure 8.6). For kin selection to operate, it is not necessary that the altruist be able to distinguish relatives from nonrelatives; it is only necessary that close relatives are more likely to benefit from altruistic acts. Although kin selection does not require kin recognition, can animals assess the degree to which other organisms are related to themselves? In some social animals, individual recognition (based on growing up together) can be used. Other species, including mice, use odor cues. The odor of each animal is genetically influenced, and the diversity of genotypes results in a diversity of odors. Mice can detect by odor which individuals are the most closely related to themselves. Mice seem to use odor-based kin-recognition when they establish communal nests. Several females share a nest and nurse each other’s offspring. A mother’s inclusive fitness is maximized if she nurses only offspring that are closely related to her. Femaleswho share a communal nest are usually related genetically.Another explanation of altruism, based on game theory, is described on the book’s Web site, under Resources: Reciprocal altruism.Figure 8.6Two examples of altruism favored by kin selection.A one-year-old Florida scrub jay (right) assists in the care and feeding of its younger siblings.A female ground squirrel (Spermophilus beldingi) stands guard against predators. If a coyote or hawk is spotted, the guard female emits an alarm call that attracts the predator and thus endangers the caller, but the alarm also warns the caller’s next of kin and thus raises her inclusive fitness.The evolution of eusocialityThe highest degree of social cooperation is developed among the truly social, or eusocial, insects. Eusocial species are recognized by the possession of three characteristics: strictly defined subgroups called castes, cooperative care of the eggs and young larvae (cooperative brood care), and an overlap between generations. Eusociality occurs in the insect order Isoptera (termites) and particularly often in the order Hymenoptera (bees, wasps, and ants). A few bird species and one mammal (the naked mole rat, a burrowing type of rodent) approach eusociality in having ‘helper’ individuals who assist in caring for their siblings, but these helpers do not form a distinct caste.Humans show some of the characteristics of eusocial behavior, but not to the extent shown by the eusocial insects. Humans have overlapping generations but often do not cooperatively care for their young anddo not usually form castes. Assisting in the care of someone else’s children (alloparental behavior) is, according to the American sociobiologist Sarah Hrdy, an important characteristic of our species (see Figure 1.4, p. 17), but the eusocial insects far surpass us in this behavior.Eusociality in termites. Termites (order Isoptera) are a group of insects related to the cockroaches. Termite colonies are founded by a single reproductive pair called the ‘king’ and ‘queen.’ The queen grows many times larger than the other colony members, her offspring, who continually feed her and raise her additional offspring.An important termite characteristic central to the understanding of their evolution is their chewing and digesting of wood. Termites can digest wood only with the help of symbiotic microorganisms (mostly flagellated unicellular organisms of the kingdom Protista) that live in their guts. The termites transmit these protists through regurgitated food passed to other members of the colony. This habit not only spreads the wood-digesting microorganisms throughout the colony, it also feeds those members of the colony, such as the queen, who do not feed themselves. In the evolution of eusociality among termites, the chewing of wood led to selection favoring the retention and transfer of the symbiotic microorganisms.Along with food and microorganisms, termites also pass chemical secretions that communicate social information to other colony members. Chemicals that are used for communication are called pheromones. Some of these chemicals are similar to hormones, except that they are secreted by one individual and produce their effects in other individuals. One such chemical, secreted by the termite queen, inhibits most other individuals in the colony from becoming reproductively mature. Thus, the passing of food and symbiotic microorganisms throughout the colony was a precondition that probably led to the evolution of termite eusociality by providing each queen with the means to chemically control the reproduction of other individuals. These other individuals form several types of sterile castes, depending on the species. Many of the nonreproductive individuals are workers that feed the queen, tend her larvae, and enlarge the colony’s living space. Other individuals serve as soldiers, fending off potential enemies that pose threats to the colony.At seasonally timed intervals, winged reproductive individuals of both sexes are produced; these winged individuals emerge from the colony all at once and embark on nuptial flights during which mating takes place. Newly mated pairs become the founders of new colonies. Meanwhile, the original colony persists for the lifetime of the queen, a period of some 10–12 years.Eusociality in the Hymenoptera. The insect order Hymenoptera (bees, wasps, and ants) has a much larger number of social species, of which an estimated 12,000 are species of ants. The American evolutionary biologist E.O. Wilson, considered to be the founder of modern sociobiology, is a specialist on ants. He has estimated that eusociality has evolved among the Hymenoptera as many as a dozen times and perhaps more. Why has eusociality evolved so many times in this one insect order, and so seldom in other animals? The clue seems to be found in hymenopteran sex determination and in its effects on inclusive fitness.The social Hymenoptera have a unique form of sex determination (called haplodiploidy). Eggs that are unfertilized, and therefore haploid, nonetheless develop, but all develop into males. Eggs that are fertilized, and therefore diploid, all develop into females. Reproduction is sexual, but each reproductive female mates only once, for life, with a single male. All cells in the male are haploid, and he contributes the same haploid set of chromosomes to all his offspring. The daughters therefore share all the same alleles from their father. (By contrast, in the more usual form of sexual reproduction found in animals like ourselves, males are diploid and their haploid gametes do not all carry the same alleles; their children do not share all their father’s alleles, but each gets a different assortment.)In both forms of sexual reproduction, each female is diploid, and her gametes carry different alleles following meiosis. Her daughters each get half of her chromosomes, and half of her alleles, but each daughter gets a different sample. For each chromosome that a female receives from her mother, there is a 50:50 chance that her sister will receive the same maternal chromosome. Thus, on average, a female shares half of her maternal chromosomes, and half of her maternal alleles, with each sister (Figure 8.7). As a result, two sisters share all of the alleles from the half of their chromosomes obtained from their father, plus half of the alleles from the half of their chromosomes obtained from their mother. Sisters therefore share ½ + ¼ = ¾ or 75% of their alleles, on average (see Figure 8.7). A female, however, only shares half of her alleles with her mother or her daughters. By neglecting her own daughters (who share only one-half of her genotype) and raising her sisters instead (who share three-fourths of her genotype, on average), she is increasing her genetic fitness. For this reason, sex determination by haplodiploidy favors the evolution of eusociality in the Hymenoptera because most females can gain greater inclusive fitness by becoming sterile workers and by helping their mother (the queen) to raise her offspring (their sisters) than by raising offspring of their own. Ancestral Hymenoptera were solitary (and many solitary species still exist), but eusociality has evolved repeatedly and independently in this group of insects (Figure 8.8).Figure 8.7Haplodiploidy in a species with a haploid chromosome number of 2. Notice the four females shown with shaded borders in the first generation. Each of these females shares between 50% and 100% of her chromosomes with the others, who are all her sisters. On average, each of these females shares ¾ of her chromosomes (R = ¾) with her sisters but only ½ of her chromosomes(R = ½) with her own daughters (the females in the second generation).The queen bee or wasp usually secretes pheromones that inhibit the sexual development of other females in the colony. Other mechanisms determine which larvae develop into queens and which into sterile workers. For example, future queens are fed a nutritious ‘royal jelly’ that contains both nutrients and chemicals that stimulate their reproductive development. Also, whenever new queens emerge, one of them (usually the one emerging first) stings the others to death and thus emerges as the undisputed queen.diploid queen gametes randomly formed by meiosis first generationhaploid males(formed from any egg if unfertilized)diploid females (formed from any egg if fertilized)haploid male gametesanother haploid malesecond-generation femalesMost of the social behavior of eusocial insects is under instinctive control; in fact, the eusocial insects represent the highest complexity that instinctive behavior has ever reached. Antisocial behavior (meaning behavior that decreases the fitness of others) does not exist in these societies because antisocial individuals are quickly eliminated.Figure 8.8Eusocial insects.A colony of ants Honeybees swarmingAre the behaviors of individuals within a species more alike than the behaviors of individuals from different species?As noted in this section, individuals share, on average, half of their genotype withTHOUGHT QUESTIONStheir siblings. Refer to the discussion of meiosis in Chapter 2 (pp. 42–44) and explain why this is so.Why should humans be interested in the social behavior of birds, frogs, or insects?Reproductive Strategies Can Alter FitnessNatural selection results in some genotypes leaving more copies of themselves in subsequent generations than other genotypes do. The manner in which these copies are produced can be called a reproductive strategy. Reproductive strategies include such features as the manner of reproduction (laying eggs or bearing live young), the litter size or number of eggs laid, the presence or absence of parental care, the presence or absence of sexual recombination, and, if there is a mating system, whether it is predominantly monogamous, polygamous, or promiscuous. Sexual behavior is an important part of reproductive strategy in many social species.Asexual versus sexual reproductionReproduction of organisms can be either sexual or asexual. Many species (including all mammals and birds) are exclusively sexual, while bacteria are predominantly asexual, and certain other species (yeasts, aphids, and a variety of plants) can reproduce either way depending on the circumstances.Asexual reproduction may be defined as reproduction without any genetic recombination. This type of reproduction has certain advantages over sexual reproduction. Within a group of organisms that includes species reproducing sexually and also species reproducing asexually, those reproducing asexually can generally do so faster and with lower energy costs. Asexual reproduction allows reproduction at an earlier age and a smaller body size, and it also avoids the costs associated with sexual reproduction. For an individual that discovers a large but finite or perishable supply of food or some other resource, asexual reproduction is an advantage because more offspring, and more generations of offspring, can be produced in a minimum of time, without any need of finding or courting a mate. Moreover, the numerous offspring are genetically identical to the original parent or founder, ensuring that favorable combinations of genes are perpetuated exactly. (The genetically identical asexual offspring of a single individual are referred to as a clone.)In contrast, sexual reproduction, reproduction with genetic recombination, is more costly than asexual reproduction because of the time and energy expended in seeking, finding, and courting a mate, and in transferring or accepting sperm. Energy is also used in synthesizing structures that attract mates, and in the mating act itself. Mate attraction also makes a sexually reproducing individual more visible to predators, exposing that individual to increased risks. A major genetic cost is that of passing only 50% of one’s alleles to each child, giving up the other half (during meiosis) to be replaced by those from one’s mate. In view of these costs, it is amazing that sexual reproduction would be so widespread in both the animal and plant kingdoms. Sexual reproduction must have some great advantage.The great advantage of sexual reproduction is genetic variety among the offspring. In the most common type of sexual reproduction, males produce sperm cells that contain the haploid number of chromosomes, and females produce eggs that are also haploid. Each sex cell (gamete) produced by an individual carries only half of that individual’s genetic material, formed during meiosis by a random choice of one chromosomefrom each pair (see Chapter 2, pp. 42–44). Because each gamete-forming cell undergoes meiosis independently, the chromosomal choices are different each time, and the gametes thus vary among themselves. The combination of gametes with the gametes of the opposite sex is also random. The result is that sexually produced offspring vary greatly in all genetically controlled traits. This may be a disadvantage if tomorrow’s (or next year’s) conditions are identical to today’s—and unchanging conditions do in fact favor asexual reproduction. However, if tomorrow’s (or next year’s) environmental conditions are uncertain, then the best hedge against this type of uncertainty is to produce many different kinds of offspring, and sexual reproduction achieves this very efficiently. What we have just said pertains not only to the common forms of sexual reproduction, but also to other forms, such as the special kind found among the social insects: however much they differ in detail, all forms of sexual reproduction are characterized by greater variation among offspring than any form of asexual reproduction.The hypothesis that sexual reproduction derives its adaptive advantage from the greater variation among the resultant offspring receives support from the study of certain insect species (such as aphids, also called plant lice) that are capable of producing either sexual or asexual generations. During the summer, when maturing crops offer dependable food supplies for several months in a row, these insects produce several asexual generations in quick succession. At the end of the season, however, these insects reproduce sexually, and the sexually produced eggs overwinter. When they emerge in the following spring, diverse genotypes of offspring find their way to the new stands of plants under new weather conditions, neither of which could have been predicted during the previous fall when the eggs were laid. Many genotypes perish, but a few survive and prosper by reproducing asexually during the new season. The important point is that the genotype that proves most fit in the spring is not necessarily the same one that produced successful offspring asexually during the preceding year. Sexual reproduction is favored whenever future conditions are uncertain, and experiments confirm that individuals laying eggs in the fall have more surviving offspring the next year if they reproduce sexually than if they reproduce asexually.Differences between the sexesIn sexually reproducing species, the two sexes are not necessarily different. Some species, such as the green alga Chlamydomonas (kingdom Plantae, phylum Chlorophyta), have male and female haploid gametes that look identical, a condition called isogamy (meaning ‘equal gametes’). But a pair of gametes may be at an advantage if at least one of them is capable of finding the other over greater distances, thus allowing more mating or mating from a wider choice of potential mates. In some cases there may also be an advantage for the resultant fertilized egg (zygote) if it possesses stored food or protective layers, each of which increases bulk. The advantages of motility and of large size can best be balanced if one of the gametes is large and the other is small and motile, a condition called anisogamy (meaning ‘unequal gametes’). The larger, nonmotile gamete is called an egg, and the smaller, motile gamete is known as a sperm.Males and females. Although it is possible that different-sized gametes could be produced by identical organisms, this does not usually happen. Instead, reproductive anatomy and behavior differ between the sexes in most species of animals and plants, and most of the familiar differences between males and females are explained within evolutionary theory as the consequences of anisogamy. Selection among sperm-producers, or males, favors the release of numerous gametes, each of which is of minimal size and maximum motility. The minimal size means that each individual sperm represents a trivial investment (in energy and materials) for the male that produces it. A male can easily produce thousands (or millions) of sperm, and he can compensate for a poor choice of mates by mating more often. Competition among males usually favors whichever one can produce the most gametes that combine successfully with the most eggs.Selection among egg-producers, or females, generally favors a larger investment of parental resources, such as stored food, in each egg. Among numerous eggs, those with the most stored food or the strongest protective layers generally have the best chance of survival. This necessarily limits the number of eggs that a female can produce, and places a premium on egg quality rather than number.Parental investment. There are further consequences of parental investment. If male parental investment is low in both energy and material costs, the price that a male pays for mating with a given female is very small. If their offspring are low in fitness (i.e., they have a small chance of survival), the male can simply mate again with other females. Low parental investment produces non-discriminating males.Females, having fewer eggs, can produce more surviving offspring if they invest more care and protection in each one. This is especially true in mammalian females, which devote much time and energy to gestation, intrauterine feeding, and lactation. Because a female’s parental investment is high, each of her offspring is more costly to her. If she mates with a low-fitness male, she greatly reduces her own fitness. She cannot simply make up for a poor choice by mating again because her capacity for repeated mating is generally limited by the large investment she must make in each of her offspring. Females thus have more at stake in each mating, and stand to gain more by choosing a mate who will father offspring who are more fit, or to lose more by choosing a mate who will father offspring who are less fit. In social species in which males vary in social status, a female can generally maximize her fitness by mating with a high-status male who can provide her and her offspring with a greater degree of protection. Selection thus favors females who are more discriminating in their mate choices, both as to social status and genetic fitness.Mating systemsThere are many types of mating systems known within sexual reproduction. In species in which care of the young requires the cooperation of both parents, parental investment tends to be high for both sexes. These conditions favor monogamy, or mating between one male and one female (Figure 8.9). If the rearing of their common offspring takes a long time, the formation of a permanent pair-bond (i.e., mating for life) is favored.Another common situation is one in which only females care for the young, but males provide protection to both female and offspring. This situation generally favors the development of one form of polygyny, a mating system in which one male mates with several females. Many mammals form polygynous mating units; for example, male fur seals come ashore during the breeding season and establish territories, which they defend against other males (see Figure 8.9). The strongest maledefends the best territory, an area where females can rear their pups within easy reach of the sea. Females are attracted to the territory (rather than to the male himself) and mate with males that hold territories. Males who lose territorial contests go off in search of other suitable territories. If they find none, they will not mate during that season.Red deer, bighorn sheep, and certain other species of hoofed mammals (ungulates) form polygynous mating units in a different way. Adult males establish a dominance hierarchy, either through ritualized threat displays or through actual fighting. The females are mostattracted to the dominant male. The dominant male gathers together as many females as he can, forming a ‘harem.’ Male social status in harem-forming species often correlates with fighting ability and with the size of horns, antlers, or other conspicuous features, so females can see at a glance which male is dominant. Females can ensure better protection against predators for themselves and their offspring by following and mating with the dominant male. Any genetic component of the characteristics correlated with social dominance is passed on to their offspring, who will thus inherit such characteristics as fighting ability, size, and the size of horns or other weapons. Nondominant (subordinate) males have fewerFigure 8.9Examples of different mating systems. mating opportunities than dominant males. Many subordinates are simply young adults who will get their turn to become dominant the following year.In addition to monogamy and polygyny, other types of mating systems include polyandry, an uncommon type in which one female mates with multiple males. The term ‘polygamy’ is sometimes used to include both polygyny and polyandry. Another mating system is promiscuity, in which members of both sexes mate with multiple partners and generally avoid forming permanent partnerships (see Figure 8.9).We have seen that reproductive behaviors, as well as other social behaviors, vary greatly between species. We have primarily looked at examples from the animal kingdom, but even bacteria show some social behavior. When bacteria grow in groups, they make different proteins than when they grow singly. Bacteria in groups can, for example, influence one another in the timing of their cell cycles and metabolic events. This type of social behavior is called quorum sensing. Plants show other social behaviors, including the secretion of chemicals that inhibit the nearby growth of other individuals. Plants also show some ability for kin recognition in that some plants can assess the ‘match’ between proteins or other molecules derived from the male pollen and the female stigma. In the next section we look more closely at social behaviors and reproductive strategies in primates, including humans.Monogamy: a family of Canada geesePolygyny: a large male fur seal surrounded by femalesPromiscuity: baboonsTHOUGHT QUESTIONSWhat are the biological definitions of ‘male’ and ‘female?’ How do these compare with cultural definitions of the same words? Do ‘male’ and ‘female’ (or ‘masculine’ and ‘feminine’) mean different things in different cultures, or at different times in history?In humans and other species, males tend to have greater muscle mass than females.Under what conditions would you expect anatomical differences (in muscle mass, antlers, or size) to evolve? Is there a reason why such differences would be favored by natural selection?Does the difference in gamete size in humans and other mammals tell us anything about our sexual behavior? Are human males ‘destined’ to be promiscuous?Primate Sociobiology Presents Added ComplexitiesPrimates are an order of mammals that includes monkeys, apes, lemurs, tarsiers, and humans. Primates are all extremely social animals. They are so interested in interacting with other members of their species that they sometimes go to great lengths to maintain an interaction or merely to look. We can devise an experiment to test this hypothesis. Set up a partition that completely obstructs the view through a window, and provide a lever that raises the partition for a predetermined length of time, affording a temporary view through the window. Most primates will then spend hours repeatedly pressing the lever and looking through the window, then going back to press the lever again for another view almost as soon as the partition falls. The rate of lever-pressing is higher if the window affords a view of moving objects (such as electric trains) rather than nonmoving objects (such as furniture). The rate is higher still if an actively moving animal is visible through the window, and it is highest of all if the view includes other primates of the same species. Is it any wonder that people also spend hours looking through windows at the world around them, especially when other people’s movements and interactions are visible? And, in addition to the live action visible through a real window, television provides a virtual window through which we can watch people interact even more.Primate social behavior and its developmentSocial skills in both human and nonhuman primates depend strongly on learning that takes place early in life. All parents and future parents should be aware of the paramount importance of early childhood experiences in all later aspects of human life. The lasting importance of learning that takes place very early in life is one of many important areas in which humans and other primates are very similar. Because of the great similarity among all primates, findings based on experiments with nonhumanprimates are often used to gain insights into human behavior, although findings in one species should not be uncritically applied from one species to another. However, when we compare the behaviors of different primate species, we usually find many more similarities than differences.Early development of behavior. As we stated earlier, the standard test for an instinct requires that an animal be raised in isolation. Raising a primate in isolation, however, results in abnormal behavior resembling that of abused children. Sigmund Freud claimed that a baby’s attachment to its mother is based initially on its need for nutrition. To test this hypothesis, Harry Harlow of the Wisconsin Primate Research Center raised infant rhesus monkeys (Macaca mulatta) with various forms of care but with no live mothers. Instead, dummy ‘mothers’ with colorful wooden ‘heads’ held baby bottles mounted in wire frames. Although the infant monkeys drank the milk, their behavior grew progressively more abnormal with time. The infants frequently cowered in the corner and were easily frightened. They formed no emotional attachments and seemed to ignore their ‘mothers’ except when they were hungry. Freud’s hypothesis was falsified because the young monkeys failed to treat the wire model as a mother. Something more than the milk supply was needed for infants to form a bond with their mothers.Harlow noticed that young monkeys liked the feel of terrycloth towels. He tried wrapping the wire mothers in a few layers of terrycloth to make them soft and clingy. The infant monkeys enjoyed clinging to these cloth-covered dummies, and the terrycloth retained the infant’s own body heat during the periods of clinging. Harlow raised infant monkeys with two dummy ‘mothers,’ with and without ter-rycloth, one of them holding a baby bottle. Young monkeys spent countless hours clinging to the terrycloth ‘mother,’ regardless of which dummy held the bottle (Figure 8.10). When exposed to a novel or frightening stimulus, the infant monkeys would run to their terrycloth ‘mothers’ to cling for reassurance. After clinging for a while, the young monkeys were sufficiently reassured that they became brave enough to inspect the previously frightening stimulus. In many cases, their curiosity finally overcame their fear. Wire dummies, in contrast, never provided the behavior-changing reassurance.Development of adult behavior. Rhesus monkeys raised with terrycloth ‘mothers’ seem to function normally until they become sexually mature, at which time behavioral deficits do appear. A normally raised male rhesus monkey ‘mounts’ a female during her reproductive cycle if she ‘presents’ to him (Figure 8.11), but the motherless males never mounted any females and seemed not to know how to behave in this situation. Motherless females did come into their reproductive cycles (their genitals swelled up and became bright pink), but they neverFigure 8.10An infant rhesus monkey raised by two dummy ‘mothers,’ one made of bare wire and the other covered with soft terrycloth. Note that the infant maintains contact with the terrycloth ‘mother,’ even while nursing from the wire dummy.Figure 8.11Normal mating behavior in rhesus monkeys.‘presented’ to any test males, and they consistently rejected all sexual advances. A few such females were artificially inseminated under anaesthesia and became pregnant. When their babies were born, they showed no signs of maternal behavior, such as picking up their infants and holding them to the breast. Instead, they either ignored or rejected their infants, in some cases so forcibly that the infants had to be removed for their own safety. Sexual behavior and maternal behavior had never been learned in these monkeys, even though their behavior had seemed normal up to the time of sexual maturity. Adult social behavior has very strong learned components in rhesus monkeys and in other higher primate species, too.Harlow continued his experiments, seeking to pinpoint what the motherless monkeys were failing to learn from the terrycloth dummies. Could the young monkeys receive a proper upbringing without a live mother? What conditions were minimally necessary? Remembering that wild juvenile primates associate with one another in play groups, Harlow let some of the young, motherless monkeys play together. He found that motherless monkeys who had opportunities both to cling to a terrycloth dummy and to play with one another developed normal adult social behaviors. By varying the length of the play period, Harlow was able to show that as little as half an hour of play per day was adequate to ensure that young monkeys would acquire normal adult behaviors. Harlow concluded that instincts were not sufficient to produce the proper sexual behavior or maternal behavior in these monkeys, but that a youthful period of social learning was also required.Rough and tumble play. Most play in primates is “rough and tumble” play in which there is frequent and repeated body contact, including pushing, pulling, and climbing—just watch young children in a schoolyard to see examples. Primate play also includes a good deal of chasing and dodging, usually followed by more rough and tumble play. Although rough and tumble play is neither sexual nor maternal, it seems to teach many lessons, such as how to handle and perhaps restrain other individuals without hurting them. Hurting another individual, whether accidentally or not, brings an adult female ‘presenting’ mounting and copulation squeals of pain, generally causing adults to intervene and break up the activity. Play also teaches taking turns at different roles: pursuer and pursued, restrainer and restrained, climber and support, etc. In the context of play, the players learn how strong or weak other individuals are, and how much rough play each will tolerate. These lessons are later refined into dominance and submission relationships with other individuals and into sexual behaviors such as those in which male monkeys mount females. Mounting behavior arises during rough and tumble play, without regard to the sex of either individual; only after sexual maturity does it take on an explicitly sexual meaning. The defense and protection of smaller individuals, including picking them up and delicately cradling them, is also learned in play. In large, mixed-age social groups, there is usually an opportunity for subadult animals to practice the behaviors related to child care.There are parallels in human behavior. Children learn many lessons in play, including cooperation, turn-taking, role-playing, counting and scorekeeping, setting and following rules, and settling arguments and disputes. They also learn a good deal about each other’s personalities: who plays fair, who cheats, who is a bully, who cries if they do not get their way, and so forth. Children often imitate adult roles in play, practicing many of the skills that they see adults using and that they may themselves use later in life: hunting, digging, child care, food preparation, useful and artistic crafts, and so on. Abused children and those deprived of the opportunities of exploratory and rough and tumble play with other children often fail to develop the proper adult social behaviors, including both marital behavior (which is much more than just sexual) and parental care.Social organization. Most primates are extremely social, but the size and complexity of social groupings vary greatly. Closely related to the species that Harry Harlow studied are the baboons, monkeys of the genus Papio. Papio hamadryas is a harem-forming, polygynous species that lives in the rocky highlands of Ethiopia. Male hamadryas baboons are often aggressive fighters, and were revered by the ancient Egyptians for this trait. The other baboons, Papio cynocephalus and related species, live on the open, grassy savannas of Africa. The savanna baboons all share a form of social organization different from that of the hamadryas. In the wild, savanna baboons hardly ever fight. They express dominance largely through gestures such as staring at an opponent, showing their teeth, or slapping the ground (Figure 8.12). We can study dominance by observing pairwise encounters (between two individuals at a time) and noting which baboon more often gets what it wants. Dominance status generally follows size and fighting strength, although it is rarely contested and outright fighting is rare. A lengthier description of baboon social organization can be found on our Web site, under Resources: Baboons.Grooming. Baboons, like other monkeys, are forever grooming one another—picking burrs and parasites from each other’s fur (see Figure 8.12). As a gesture of friendliness, grooming is generally reciprocated, with groomer and recipient taking turns. Grooming is a pleasurable activity, and it helps form many social bonds. Infants and juveniles are often groomed by their mothers. Females who are not yet mothers themselves often practice grooming behavior and infant care. This ‘mother-in-training’ behavior, called ‘allomothering’ or ‘aunt behavior,’ isFigure 8.12Examples of social behavior in monkeys.Baboons grooming one anothervery important in many primate species, including humans. Through such experiences, older juvenile primates of both sexes learn the behavior patterns essential to parenting, while younger primates gain social experiences, learning experiences, and even substitute parents in the event of the parent’s death or temporary removal.Human examples of allomothering include holding and feeding other people’s children, playing with children, and, of course, baby-sitting.Reproductive strategies among primatesStudies of primate behavior before the late 1960s were in most cases written by male scientists and tended to emphasize male behavior anddominance relations among males. Males were often described as making choices, while females were often depicted as either passive or ‘coy.’ Beginning with the early work of primatologists Jeanne Altmann (American), Phyllis Jay (American), and Jane Goodall (English), relationships among female primates began to receive equal or greater attention. The primatologists of the subsequent generation conducted many important new studies that focused on the social behavior of female primates.One primatologist who has changed our views of primate sexual biology is Sarah Hrdy, whose sociobiology is influ-Threat display of a male hamadryas baboon, showing his large canine teethGrooming behavior in rhesus monkeys enced by a feminist outlook. Female primates, according to Hrdy, are much more sophisticated than previous researchers had imagined. Whereas the adult males use rather obvious means to maximize their inclusive fitness, Hrdy discovered that the means used by females were considerably more subtle and usually involved influencing the behavior of the males.In her work on langur monkeys in India, Hrdy discovered the important ways in which female monkeys, although subordinate in power and strength to males, nevertheless managed to influence male reproductive choices and male social behavior to the female’s own advantage. Male primates differ from one another in the number of offspring that they leave, and female primates frequently modify what males must do to achieve reproductive success. Female primates can often maximize their own reproductive success by the ways in which they influence male social behavior. Hrdy identified at least five ways in which female primates can maximize their reproductive fitness:by choosing their mates,by influencing males to support and protect them,by competing with other females for resources,by cooperating with other females (usually close relatives),by increased efficiency in daily activities such as locomotion and obtaining food.Through the work of these primatologists, we now know that females make important choices of their own and solicit male attention for a variety of reasons, showing that it often pays for them to be flirtatious rather than coy. For example, females of many species can mate with males who are not their usual partners, and they have often been observed to mate at times when they were already pregnant or otherwise unable to produce new offspring. Males can generally increase their reproductive fitness by mating with as many females as they can, indiscriminately. The optimal behavior for a female, however, depends on her own fitness and social status, as well as that of her possible mates. If a female is of high status herself, and is mated to a high-status male, then she has nothing to gain from mating with a lower-ranking male. In contrast, a female of low status, or one mated to a low-status male, could potentially increase her fitness by mating additionally with a high-status male. If he sires one of her offspring, then she has produced a higher-status offspring and raised her own fitness as a result. That is because the offspring of higher-status males have more opportunities to mate; therefore, females can maximize their fitness (leave more grandchildren) if they raise the offspring of high-ranking males. Moreover, even if their mating produces no offspring at all, the high-status male who has mated with her will maximize his fitness by protecting any female that he has mated with, as well as her subsequent offspring, because he would be operating under the assumption that these offspring might be his. Thus, females can gain important advantages from liaisons with high-ranking males, even at times when ovulation has not occurred and when subsequent pregnancy and childbirth are not possible.Hrdy also discovered that male primates are sometimes infanticidal,and that female willingness to mate with powerful males was sometimes a strategy to discourage their infanticidal tendencies. Infanticide may occur among certain primate species whenever a new dominant male takes over a group. The new male can increase his fitness if he kills infants that are not his, especially if their mothers are lactating. Lactation inhibits the female reproductive cycle in most mammalian species; infanticide by the male causes lactation to end. Females enter estrus and the male gains access sooner to reproductive females. Once he has mated and produced offspring, however, the male will maximize his fitness if he defends all his mates and their offspring.One of the many consequences of primate reproductive strategies is a difference between the sexes in how they pay attention to social rankings. Males in socially ranked species must pay attention to their own rank and status—they must remember who has ever threatened them or been intimidated by them. Females, however, must know much more, because each female must not only know her own status, but also that of every male in the group. In order to know whether one potential mate ranks higher than another, she must pay attention to all the social interactions among the males. In social species, females therefore generally take more interest than males in knowing about the social interactions of all other members of the group and in learning the status of all the males. Those who are better at paying attention to male–male interactions and correctly judging each male’s social status and genetic fitness are at a selective advantage because they are better able to maximize their fitness by their behavior toward these males.Both Hrdy and Jane Goodall have observed several instances in which competition between females produced outright hostility, even infanticide. Arguing from a sociobiological perspective, Hrdy explained that competition among unrelated females should be expected when their genetic self-interests are in conflict. A universal sisterhood, in which all females cooperate as a unit, would therefore never evolve. In evolutionary terms, such a sisterhood would not be a stable strategy, because an individual female would always be able to ‘cheat’ by refusing to cooperate, and by doing so she would raise her fitness and be favored by natural selection. Because evolution would never be expected to produce cooperative sisterhoods among unrelated females, Hrdy suggests that women who share her desire for such cooperative sisterhoods should strive to create them socially. Humans are not prisoners of biological destiny and are able to create social groupings and social behaviors that have not evolved.Some examples of human behaviorsMuch interest has focused on certain human behaviors and on the extent to which these behaviors are learned or inherited. Behaviors disapproved of by large segments of society have generally attracted the most attention. People who wish to change behavior that has a strong learned component generally seek to find how it is learned and how an alternative form of behavior can be learned instead. If the behavior has a strong inherited component, it will be more difficult to bring about change through education. Other forms of intervention that might be more appropriate in such cases include trying to identify any genes involved in the behavior. However, most of the behaviors of interest are complex and are probably influenced by many genes, making it harder to identify any of them or to modify them in any meaningful way.We also hasten to add that political motives are often suspected of those who write about human behavior or who try to apply what we know of other species to the understanding of human behavior. History has taught us that various oppressors have claimed scientific support to justify slavery, political repression, and genocide. (The Nazis come to mind as the most obvious example, but there have been many others.) There is thus reason for caution, but sometimes the reactions have become uncivil and tempers have run high. Some biologists who intended no harm to anyone have been yelled at by disapproving crowds and have had eggs thrown at them. There are people, in other words, who fear that scientific study may again be used to justify unspeakable horror.Aggression. Konrad Lorenz was a German scientist who studied animal behavior. He first won recognition (including a Nobel Prize) for his studies on imprinting, a form of learning that occurs early in life. In his later years, Lorenz wrote several controversial books in which he claimed that many human behaviors are instinctive. For example, in his book On Aggression, Lorenz claimed that aggression is largely instinctive in humans as well as other animals. As evidence, Lorenz argued first that aggression is widespread in many animal species and in various human societies. Second, he argued that the facial expressions and other gestures that accompany aggression and aggressive threats are similar in humans and animals and are also similar across many human societies.Other scientists, however, have marshalled considerable evidencethat aggression in humans has strong learned components.Aggression takes many different forms in different societies, which use different weapons and different fighting traditions. If aggression were entirely instinctive, one would not expect it to be so variable.Aggression is more prevalent in those societies that encourage it, and it generally takes the form that the society encourages. In the many societies that encourage aggression only in males or only in certain age groups, it occurs primarily in the groups in which it is encouraged. In societies that discourage aggression, it is much less common.Within any society, some individuals are more aggressive than others. Individuals trained to be aggressive become aggressive, while most people raised to be less aggressive become less aggressive. We would not expect such large individual differences if aggression were inherited.When aggressive behavior is desired, as in the military or in sports such as boxing and judo, it must be taught and practiced frequently.Two special forms of aggression that have received a lot of attention are child abuse and rape. Studies examining criminal records in various countries all over the world have shown that child abuse among humans follows the same patterns as infanticide in other primate species. In particular, stepfathers (who are genetically unrelated to the children who live with them) are up to 100 times more likely to abuse or kill the children in their care than are genetic fathers.Feminist writers such as Susan Brownmiller have portrayed rape, or forcible sexual intercourse, as an attempt by the rapist to dominate and control his victim, and thus as a crime of violence rather than of sex. Against this idea, sociobiologists Randy Thornhill and Craig Palmer argue that rape is very much about sex. They use statistical records from rape crisis centers to show that victims are most often in the prime reproductive age range and that married rape victims feel more heavily traumatized than unmarried ones. They claim that a predisposition to rape persists because rape does occasionally produce children who perpetuate the genes of the rapist. Therefore, these authors argue, rape is natural, though they hasten to add that it is still reprehensible behavior. Their hypothesis does not, however, explain why the overwhelming majority of men are not rapists.Many studies show that most women prefer as mates men who are good-looking, healthy, strong, skillful, kind, respected by others, and high in social status and wealth. Thornhill and Palmer say that “men might resort to rape when they are socially disenfranchised, and thus unable to gain access to women through looks, wealth, or status.” According to this hypothesis, the men who become rapists can leave more offspring if they rape than if they do not, because they are usually the men that women are unlikely to choose as mates.Barbara Ehrenreich, a critic of the Thornhill–Palmer hypothesis, emphasizes that rapists make inferior husbands and fathers, and that the children of rape are thus far less fit than other children. The mothers of these children have been traumatized, and their fathers are in most cases gone, and when present they are neither good fathers nor good role models. Compared with the men that women would choose as mates, rapists are inferior in social standing, inferior in fitness, and inferior in their ability to raise fit children. This may explain why most men are not rapists: they can produce more children, and contribute as fathers to their children’s fitness, by cultivating the behaviors that women value. The children of these men and the women who choose to marry them usually attain higher social status and are more socially and psychologically equipped to enter into normal and stable relationships themselves. They tend to leave more future children and are thus far more fit than the children born of rape.Alcoholism. Alcoholism is a complex form of behavior that seems to have both learned and inherited components. To complicate matters, there are various degrees of alcoholism, and many individuals are classified as alcoholics by some criteria and not others. However, the greatest complication arises from the heterogeneity of the disorder: alcoholism manifests itself differently in men and in women, and it may also have different characteristics in different social classes.Recent studies show that alcoholism may in fact exist in two or more separate forms. Type I alcoholism, also called late-onset or milieulimited, typically arises after age 25 and is common in both sexes. It is characterized by psychological or emotional dependence (or loss of control), by guilt, and by fear of further dependence. This type of alcoholism frequently responds well to treatment. By contrast, type II alcoholism, also called male-limited, early-onset, or antisocial alcoholism, typically arises during the teenage years and is common in males only. It manifests itself in alcohol-seeking behavior, in novelty-seeking or risk-taking behavior generally, and in frequent impulsive and antisocial behavior including alcohol-related fighting and arrests. This type of alcoholism responds poorly to conventional forms of treatment.Adoption studies in Denmark, Sweden, and the United States suggest that a predisposition for type II alcoholism may be inherited. The largest study, of 1775 adoptees in Sweden, found that the rate of alcoholism among the biological sons of type II alcoholic fathers raised in families without alcoholics was nine times the rate among other adoptees, including those adopted into type II alcoholic households. Type I alcoholism, however, shows a much smaller hereditary influence and may instead be subject to strong environmental influences. Some experts suggest that type I alcoholism is still heterogeneous and should be subdivided further. Studies on alcoholism among twins show a higher rate of concordance in identical twins than in fraternal twins, meaning that, if one twin is an alcoholic, there is greater probability that the other is also an alcoholic if the twins are identical than if the twins are fraternal. (Asdescribed in Chapter 3 (pp. 71–72), a rate of concordance is the fraction of individuals who match in a certain trait.) The concordance is greater for type II alcoholism than for type I.Sexual orientation. Some people regard variations in sexual orientation, including homosexuality, as innate and unchangeable, while others view them as learned behavior patterns that are subject to change. The available evidence, which is not very extensive, was summarized and reviewed in two books by the English-born neurobiologist Simon LeVay. Some small differences were observed between the brain structures of homosexual men and heterosexual men, but many of the homosexual men in the study had died from AIDS, so it is uncertain whether these differences resulted from AIDS or pre-dated the onset of that disease. If a difference in brain structure could be demonstrated between homosexual and heterosexual men, other questions would remain to be answered: did the structural difference precede the sexual orientation, or might the structural change have resulted from some aspect of a lifestyle difference? Scientists are only just beginning to examine such questions in homosexual men; studies examining lesbian women are even rarer.Studies have been conducted on homosexual males who have twin brothers. The rate of concordance is higher for identical twins than for fraternal twins, meaning that, if one twin is homosexual, there is a much higher probability that the other twin is also homosexual if he is an identical twin than if he is a fraternal twin. Such a result is suggestive of at least some genetic influence, but the very real methodological problems of such twin studies makes it very difficult to rule out other possible influences. The biggest shortcoming of twin studies is that the environments in which the twins are raised are never chosen at random and are usually very similar, even in cases of adoption.THOUGHT QUESTIONSTo what extent can sociobiological findings on animals be extrapolated to humans? Are animal studies relevant at all to the study of human behaviors such as alcoholism or homosexuality?How important are fathers in early childhood development? What important social skills do children learn from interacting with their mothers? With their fathers? What do children learn from watching their parents interact with one another? What happens in families inwhich no father is present? What happens when no mother is present?Think of the many ways in which humans learn (and subsequently practice) the social skill of evaluating the social status and motives of others. How much do we learn (or what skills do we exercise and practice) from play, from small-group discussions, from gossip, from novels, or from television? Do males and females participate in these activities in the same way? Why, or why not?Concluding RemarksSociobiology, the comparative study of social behavior and social groups among organisms, is a subfield within evolutionary biology. Much of social behavior is learned, but only those aspects of social behavior that are inherited are subject to natural selection and therefore to evolutionary change. Sociobiology therefore focuses on inherited behaviors or capacities, although all sociobiologists agree that learning can modify those behaviors in many species. Often it is a predisposition for a behavior, or a capacity to learn a behavior, that is inherited, not the behavior itself. Sociobiology can predict when natural selection will favor altruism, social groups of differing sizes, behavior that is stereotyped as opposed to variable, or behavior that differs between the sexes. Many such hypotheses have already withstood repeated testing.In humans, even though some components of behavior are inherited, every behavior can also be modified by learning. Twin studies, adoption studies, cross-cultural studies, and studies of other species can all provide important clues to the understanding of human behavior patterns. Many human behaviors vary across cultures; many are also strongly influenced by early childhood experiences. One of the most effective and cost-efficient ways in which we can improve human society is to provide each and every child with a safe childhood full of experiences from which to learn.Chapter SummarySociobiology is the evolutionary study of social behavior and social organization among all types of organisms.Summary to Chapter 8 279Organisms live in social groups because it affords such advantages as group defense, help in finding and exploiting food resources, and greater reproductive opportunities.Altruistic behavior is favored if it contributes to inclusive fitnessthrough kin selection.Inclusive fitness has also favored the evolution of social cooperation andeusocial species.Among reproductive strategies, asexual reproduction is favored by natural selection in situations in which a quickly produced series of uniform offspring are advantageous, but sexual reproduction is favored whenever future conditions are uncertain and a greater variety of offspring is a greater advantage.Among sexually reproducing species, there are many different mating systems, including monogamy, polyandry, polygyny, and promiscuity.In many species, different levels of parental investment favor different reproductive strategies in females (egg producers) and in males (sperm producers).All behavioral characteristics that have been closely studied are influenced by both genetic and environmental influences to various degrees.Behaviors that can be performed without the opportunity for prior learning are considered innate, and innate behaviors that are complex are called instincts.In animal species, behaviors related to mating and courtship are more often instincts, while learning has a stronger influence on most locomotor behaviors.Learned behavior is highly important among primates, especially among humans.PRACTICE QUESTIONSFor each of the following human behaviors, state at least one piece of evidence pointing to an important learned component for the behavior:eating with utensilsspeaking English
to khazar
For each of the following behaviors, present an argument for an important innate component of the behavior: tail wagging in dogs mooing in cows smiling in humans Present at least one argument that supports each of the following statements: touching playing the piano has important learned components that playing the piano has important innate components List at least six research methods used in sociobiology. In a variety of species, which of the following behaviors is most likely to have strong instinctual components? attract a mate climb a tree find and catch food move about its habitat None of the above natural selection favors instinctual control of behavior in all of the following situations except: in short-lived species - deceiving prey - during courtship or mating calls - sudden danger escape - build a nest or weave a web - Which of the following does NOT fit the definition of an altruistic act? leaves money for charity in his will; a taxi driver runs a red light to get a pregnant woman to the hospital in time for the delivery; a man flees traffic to save a small child; in a different group than the others?
ants
bees
termites
wasps
Which of the following situations favors sexual reproduction? Microorganisms that reproduce in a human host Fungi that grow on a fallen tree as it decays Insects or worms that feed on a large and reliable food supply Insects that colonize new food sources by laying eggs on them What are the three conditions that define eusociality? How is kin selection defined? Problems Is the earth overpopulated? How fast is the human population growing? Why a population explosion could harm social welfare? What methods are available to people who want to control their reproduction? ? Can we reduce population growth and its effects? Population ecology (populations, population densities, growth rates, carrying capacity, population regulation) Reproductive biology (reproductive anatomy, reproductive physiology, reproductive cycles, hormonal control) Biosphere (human influences, overpopulation) and its effects, resource use, habitat change) Chapter Outline Demography helps predict future population size Population growth Malthusian analysis of population growth Growth within limits Demographic change Human reproductive biology helps us understand the fertility and infertility Reproductive anatomy and physiology Deterioration of fertility Assisted reproduction Can we reduce the population? growth and its effects? and Ethical Opposition to Birth Control Population Control Movements Women's Education Population Impact Control 9281 The Population Explosion Imagine a world where people have to share a room with 4 to 12 other people. Having your own room is a rare luxury. In fact, people who have a house consider themselves lucky because many people do not have a house. Drinking water is in short supply every summer, and overburdened sewage systems constantly collapse; many millions do not have sewerage. Jobs are rare, and high-paying jobs are almost unheard of. Beggars roam every street and every trash can is constantly searched by hungry people looking for something to eat. Some parts of the world are already experiencing these conditions. Some experts predict that such a future could be in store for all of us unless large-scale action is taken soon to control population growth. The Earth is currently experiencing the fastest population growth in all of human history. From 2.5 billion people in 1950, the total world population more than doubled to 6 billion in 1999 (Figure 9.1). At current growth rates, the world population will double again in about 38 years. Every year the world population grows by about 94 million people. In this chapter, we consider the factors that control population size and growth rate, including biological population control, which operates independently of any conscious planning. The ecological principles we discuss include patterns of population growth, limits to growth, and some of the consequences of excessive growth. Although we focus primarily on human populations, all of these ecological principles apply equally to populations of other organisms. As with many other topics in this book, population growth cannot be seen as a purely biological problem. Population growth and its control have political, religious, and ethical dimensions, so we also consider some of these factors. In addition, in light of the growth of the world population, research on the biology of infertility is also increasing, also because more and more couples who cannot have children of their own use these reproductive therapies. Both the growth of the world's population and individual fertility and infertility raise ethical questions. We saw earlier (Chapter 1) that the limits between the individual good and the social good are one of the issues of ethics. Biology can inform ethical debate by assessing biological risks to individuals and society in different settings.282 Demography helps predict future population size The study of biological factors that influence the size of populations is called population ecology; The study of the human population in numerical terms is called demography. Remember that a population is defined as a set of potentially interbreeding individuals in a given geographic location at a given time (see also Chapter 5, p. 151). Our ability to understand population growth depends on our ability to make predictions based on both population ecology and demography. Since populations are large aggregations, we need mathematical models to make these predictions and to study the factors that can affect and potentially retard population growth. These mathematical models were originally developed from the study of bacterial populations, but they relate to the growth of all other species, including humans. Mathematical models of population growth begin with the collection of census data. A census is at least a census of all the people living in a given area, usually within recognized political boundaries. Early censuses were often inaccurate, and opposition from the population being counted (who did not want to pay taxes) only added to the inaccuracy. Furthermore, these initial censuses were almost never repeated later on the same stable frontiers, the only conditions under which population growth could be accurately assessed. The United States conducted the first state census of any modern nation in 1790 to obtain proportional representation from the various states in Congress. (This remains one of the most important functions of the US Census today.) In the first decades of the 19th century, most European nations began and continued to conduct censuses at regular intervals. The size of a population depends on its birth rate, its death rate and the relationship between the two. For a given period, the birth rate B of a population is found by dividing the number. Figure 9.1 The graph shows the growth of the world population. Inset shows a street scene in Quito, Ecuador. 0 1000 AD 2000 hunting and gathering phase agricultural phase industrial phase of births in this period by number of individuals that are already part of the population, N: B (every year) = number of births per year. The birth rate, like any other rate, is always a fraction where one number is divided by another. To illustrate with some real numbers, if there are 10,000 people in a population (N = 10,000) and 1,000 babies are born that year, the birth rate will be B = 1,000/10,000 = 1/10 = 0.1 per year or 10% per year. year year The death rate D (also called death rate) is determined similarly to the birth rate and represents the proportion of the population that dies within the relevant time interval: D = number of deaths per year N Keep in mind Note that N, a population size, falls into the equations for both the birth rate and the death rate because both are expressed in terms of the population, that is, H. Both are fractions of N. At the end of the year , the population will have changed because N has increased by the number of births and decreased by the number of deaths. To express this mathematically, the above equations can be rearranged and then combined. Rearranging the birth rate equation we get the number of births per year = B N and rearranging the death rate equation we get the number of deaths per year = D NT. So, to find the change in N per year, we add the births and subtract the deaths to get the change in N per year = B N - DN, we have dN/dT = B N - D NorthN/dT = (B – D) NThe A quantity (B – D) is called the growth rate and is symbolized as r. It is the difference between the birth rate and the death rate. dN/dT = r NA The population increases when its birth rate, B, exceeds its death rate, D, in which case r is positive. If B = D, then r = 0 and the population is stable and neither increases nor decreases. A population whose death rate exceeds its birth rate is in decline and r is negative. The growth rates for 130 different countries are shown in Figure 9.2A. The growth rate does not correlate with population density (number of people per square kilometer, Figure 9.2B). Some nations with high growth rates have low population densities (for example, Afghanistan and Mali), although the density is expected to increase as long as the growth rate is positive. Current data on population density and population growth rates can be found on our website (under Resources: Population Data). The above discussion assumed a “closed” population that is not affected by immigration or emigration. This is a safe assumption for the world as a whole, but for a single country or region we need to add terms for immigration (inputs) and emigration (inputs) as well. The United States, for example, currently has a birth rate that is not much higher than its death rate, but the population continues to grow because more people move to the United States from other countries than leave the United States at home each year. . In fact, a fifth or more of the annual population growth in the United States comes from immigration. To include migration rates in the calculation of r, we need to write = B – D + i – m, where i is the immigration rate (the number of immigrants in a year divided by the population size) and m is the emigration defined in the similar way Figure 9.2 (A) Population growth rates® and (B) population densities around the world. Today, in most nations, population growth results primarily from an excess of births over deaths, not from an excess of immigration over emigration. In the 1990s, the US population seemed to have struck a balance between birth and death rates. However, more recently, the birth rate (about 1.8% per year, or one birth every 7 seconds) has increased by about twice the death rate (about 0.9% per year, or one death every 14 seconds), and there is still an excess of immigration over emigration. The net change is a population increase of about one person every 11 seconds in the United States. Many factors, some of which may be temporary, have contributed to recent changes. For example, many "baby boomers" (people born between 1945 and 1960) began having more children many years after becoming parents for the first time, and there was also an increase in the number of people who remarried and formed second families. family. . Exponential (geometric) growth. Although the definition of the term r can include both immigration and emigration, the general equation for the growth rate has not changed and remains dN/dT = rN The type of growth described by this equation is an example of geometric growth. A geometric series is one in which each number is multiplied by a constant to produce the next number in the series. For example, 1, 2, 4, 8, 16,... is a geometric progression in which each number is multiplied by 2 to get the next number. The growth rate equation is a geometric series because each new value of N results from multiplying the previous value by 1 + r. (Another well-known example of geometric growth is the growth of money with compound interest.) Geometric growth always leads to a rapid increase after an initial start because the growth curve points sharply upwards. Geometric growth is also known as exponential growth because the expression for population growth can also be written as N=N0erT, where N is the size of the population at time T,N0is the initial size of the population (at time T=0), e is the base of the natural logarithms (approximately 2.71828) and r is the growth rate. In this way, the constant by which each number is multiplied appears as an exponent, hence the term exponential growth. The same equation can be used to describe populations of bacteria, fish, or humans, although different units of time (minutes, months, or years) can be used in each case. Plotting this equation gives a growth curve like the blue line in Figure 9.3. (Logistic growth, also shown in Figure 9.3, is explained later.) For populations that grow exponentially (geometrically), we can calculate the doubling time, that is, the time it takes for the population to double. Mathematically, the doubling time is expressed as doubling time = 0.69315/r, where the number 0.69315 is the natural logarithm of 2. In 1993, the United Nations calculated the world population growth rate to be 1.8% per year, which will result in a doubling for every 0. 69315/0.018 = 38.5 years As we have seen, the value of r varies from place to place (see Figure 9.2A). The fastest growing nations have growth rates of 4% or more, which will cause them to double their population every 17.3 years or faster. Many other nations are growing at around 3% per year, doubling their population every 23.1 years. Malthusian analysis of population growth The world's population has been increasing for a long time, but the rate of change was slow before modern times (see Figure 9.1). During the 17th and 18th centuries, several European countries experienced large population booms, contributing to the many motivations for sending out expeditions to find and colonize new lands. The need to clothe the growing population prompted innovations that made textile production more efficient, marking the beginning of the Industrial Revolution. At the beginning of the industrial revolution, philosophers and economists began to pay attention to the phenomenon of population growth. David Hume and Benjamin Franklin described population growth as a blessing to civilization. The first to emphasize the negative consequences of population growth was Thomas Robert Malthus. In his essay on the principle of population (1798), Malthus explained the following dilemma: A population tends to grow geometrically when its growth is not controlled. (As we saw earlier, a geometric series is one in which each number is multiplied by a constant to get the next number.) The amount of food available has only increased arithmetically, according to Malthus. (An arithmetic series, such as 3, 4, 5, 6, 7, ..., is one in which a constant, in this case 1, is added to each number to get the next number.) Because the population is growing faster as the food supply grows, the population exacerbates human misery and poverty, especially among the lower classes. Malthus divided the factors that control population growth into two broad categories, which he called preventive controls and positive controls. Medical examinations were the ones that could prevent births. These were generally voluntary measures at the individual level. Figure 9.3 Exponential growth versus logistic growth. The steeper (vertical) the slope, the faster the growth rate. The exponential growth graph always has a J-shaped characteristic curve (blue). (also called "moral restraint"), small families, and various forms of "addiction" (practices Malthus condemned, including birth control and homosexuality). Positive population checks would automatically be performed after births, if preventive checks were not sufficient. Malthus identified positive controls as overpopulation, poverty, epidemics, rising crime rates, war, famine, and starvation. Malthus opposed the social legislation of his day because he believed that any measure to improve the situation of the poor would only encourage them to reproduce more rapidly, further outstripping their food supply and worsening their own misery. One result of this way of thinking was the 19th century theory that reduced war to the economic needs of each nation's population, known as the economic theory of the level of war before disaster returns. This phenomenon also occurs after many wars and difficult economic times (see "baby boom" in the years after World War II). Such events show that the growth potential of a population is much greater than is commonly believed. The actual population growth rate is kept below the potential growth rate by positive and preventive controls. Throughout the 19th and early 20th centuries, technological advances in agriculture, particularly mechanized farming and the use of chemical fertilizers, resulted in higher crop yields, and prosperous nations ensured an ample supply of food for growing populations. European demographic crises were also mitigated in many cases by large-scale emigration to other continents. Malthus and his dire predictions of famine and misery have been largely forgotten. In the aftermath of World War II, attempts to deal with poverty, disease, and food shortages around the world were met with the harsh reality that population growth exacerbated all of these problems. Improvements in public health (in public sanitation, mosquito control, vaccination against infectious diseases, and general medical care) have reduced mortality rates, particularly among the young. The result, in many cases, has been incredible population growth. Population growth has affected different countries unevenly. Many nations in the developing world (those countries that have not yet industrialized) have sought to diversify their economies, modernize their industries, and improve their standards of living. Improvements in health care and sanitation accelerated after 1950, resulting in more births and fewer deaths; soon these nations found their financial and other resources dwindling as their populations continued to increase. In other words, economic development has been hampered by population growth, and many of the world's developing leaders are increasingly concerned. Without great wealth, the housing and other needs of the growing population could not be met. The positive controls that Malthus intended worked. Developing countries faced a demographic crisis (see Figure 9.1). The demographic crisis in the industrialized countries of North America, Europe, and Japan took a different form: wealth was diverted toward additional housing, roads, sewage, and necessary services. However, this development may not be sustainable in the long term, since it depends on the use of non-renewable resources such as fossil fuels and soil (see chapters 11 and 18) and on imported resources and products from less developed countries, leaving them with something less. The diversion of non-renewable resources cannot sustain stable or growing populations indefinitely. By redirecting resources, wealthy nations can slow, but not prevent, the effects of global population growth. Growth in limits Malthus's assumption of an arithmetic increase in the food supply has been disputed. Although the limited data available for Malthus was consistent with an arithmetic increase, there is no biological or other theory as to why this should happen. However, most biologists agree with Malthus that the growth of the food supply has been slower than the growth of the population. One reason is that at each stage in which one species of plant or animal becomes food for another, there is a loss of energy, a topic we will discuss in more detail in Chapter 11. How Food and Other Resources Increase slower than population, any exponentially growing population will exceed its supply of food and other resources, including available space in its habitat. Of course, no population can continue to grow exponentially. After a population has grown exponentially over a period of time, it typically follows a pattern called logistic growth. Logistics growth. Logistic growth has been demonstrated in all sorts of experimental populations, and we are not aware of any biological reason why this would not apply to human populations as well. Logistic growth can be modeled mathematically by the equation dN/dT = rN(K-N)/KIn. In this equation, K is a new quantity called the carrying capacity of the environment. Like N, K is a number, not a rate. K refers to the maximum population size that the environment can support indefinitely. As the population size approaches this carrying capacity, population growth slows (symbolized by dN/dT), and when N = K, population growth is zero (Figures 9.3 and 9.4). . If the population Figure 9.4 Different logistic growth curves Shape of a logistic growth curve Different initial population sizes (N0)8K©Different values of K1086420timetimetimeDifferent rates of increase ®Ktime reaches whatever carrying capacity is imposed by the environment (see Figure 9.4C), the birth and death rates are balanced. If the population size overshoots K, then a population crash follows in which deaths outnumber births and the population size declines to the carrying capacity.K is related to the amount of space in an environment and the other resources available, including the amount of energy that is in a form that can be used by living organisms. For animal or plant species living in an unchanging environment, K is generally constant. For our own species, K varies with changes in technology, especially technology that gets more usable energy from the same environment, for example by increases in the efficiency of energy use or of food production. A certain amount of land may support a particular population size of hunters and gatherers at a low carrying capacity (a low value of K). The development of agriculture generally results in an increased carrying capacity, and the industrial revolution (including the use of tractors and chemical fertilizers in agriculture) increases it still further.Humans can avoid an environmentally imposed population crash by limiting the birth rate before the population reaches its carrying capacity; in addition, we need to consider the effects of human populations on the populations of other species. When two species interact, either one may modify the effective carrying capacity of the environment for the population size of the other. Population ecologists define competition as a type of interaction in which a species diminishes the population size of another. An increasing human population diminishes the sustainable population size of all species with which we compete, and is driving many of these other species toward extinction (see Chapter 18).K-selection andr-selection. Biological species can have very different types of population structures and life cycles (see Chapter 8). Two basic types of population growth are those that are limited byK-selection and those that are limited byr-selection (Table 9.1). Each is favored by natural selection, but in different sets of circumstances. In environments where favorable conditions can change rapidly or disappear, high mortality rates are common, and natural selection favors prodigious reproduction of offspring (high r, therefore r-selection) to compensate for this devastating mortality. In more stable environments, population sizes stay close to carrying capacity (K), and natural selection favors efficient use of resources, especially energy. In K-selection, the advantage generally goes to whoever can most efficiently convert food resources into new adults of the next generation. Humans are an example of a K-selected species.Demographic transitionBecause humans are a K-selected species, human population increases in the past have coincided with major advances in technology that have allowed the carrying capacity (K) to reach new levels. The development of agriculture made it possible for human populations to increase well above the size permitted by hunting and gathering (see Figure 9.1).Most of our understanding of the changes that accompany a population increase comes from studying the growth of a population with changes in economic development. Our current model of this process describes it as a demographic transition, characterized by an orderly succession of stages.Stages of a demographic transition. As shown in Figure 9.5, the first stage of a demographic transition is a stable population in which a high death rate is balanced by a high birth rate. Population growth is, therefore, zero. Over the centuries, traditional societies with high death rates (especially from infant mortality and childhood infections) developed customs that encouraged high birth rates. In other words, high mortality rates encourage high birth rates; this is the pre-industrialized stage. Demographers estimate that overall mortality rates held steady or declined slowly in pre-industrial Europe, withFigure 9.5Idealized stages of a demographic transition. Some authorities recognize only three stages by combining the middle two. occasional but temporary upsurges during wars and epidemics such as the great bubonic plague (the black death) that decimated European populations in the 1300s.The second stage of the process is a period of exponential growth in which the population size climbs to a new high. This is brought about by technological changes (including industrialization) that result in falling mortality rates, or death control. In Malthusian terms, the improvements (in sanitation, health care, and nutrition, for example) result in the alleviation of positive checks and thus a lowering of D. However, it always takes at least a few generations for the cultural values and customs to change so as to permit a matching decline in birth rates. In the meantime, the memory of high death rates in the recent past continues toTable 9.1higherlower higherlowerstage 2 stage 3population increasetimetimeDifferences between K-selected and r-selected species.K-SELECTION r-SELECTIONEcological conditions Favorable conditions dependable and change slowly Unstable; very favorable and very unfavorable conditions (if at all) over time. appear and disappear erratically and unpredictably.Population size Stable, at or near the carrying capacity (K). Fluctuates greatly over time, both above and below thecarrying capacity; devastating mass mortality is frequent and often unpredictable.Values of r Low to moderate r; population growth is slower even High r leads to very rapid population growth under when conditions are favorable. favorable conditions, which compensates for massmortality under unfavorable conditions.Reproduction Always sexual. Either asexual or sexual.Body size at reproduction Natural selection favors reproduction at a large Natural selection favors reproduction at a small body size body size. and a young age.Reproductive rate Low; few offspring produced at once. High; many eggs, seeds, or other reproductive stagesproduced at once.Frequency of reproduction Repeated many times throughout life. Usually confined to a single occasion.Offspring size Offspring are individually large, and each represents a Released (as eggs or immature stages) at a small size, and large proportion of its parents’ reproductive output. widely scattered; each represents only a tiny fraction of itsparents’ reproductive output.Parental investment Generally high; may include provisioning of food for Little or no parental care or investment. offspring and extensive parental care.Dispersal Dispersal of the population to new locations is generally High capacity for dispersal (spread of the population) to slow. Newly founded populations grow more slowly. new habitats and locations. Most new locations areunsuitable, but the occasional favorable one permits a rapid explosion in numbers.Mortality pattern Most individuals live their full life span and die at an Mortality is extremely high among eggs, seeds, or larvae; advanced age. most deaths occur very early in life.Examples Humans, cows, elephants Carrion-feeding beetles, tapeworms, weeds encourage high birth rates. In some cases, the birth rate may even rise as the result of better nutrition and the improved physiological condition and reproductive health of prospective mothers. The combination of high birth rates and lower death rates causes the population growth that characterizes the middle of the demographic transition.The third stage of the transition is marked by a decline in birth rates as the population adjusts to new conditions and as the incentives for high birth rates are removed. Population growth follows the logistic growth equation during this stage. As the birth rate declines to match the new lower mortality rate, the population once again stabilizes, but at a larger population size (and a larger K) than before. The demographic transition is complete.England’s demographic transition began in the early 1700s and took some 250 to 300 years to complete. Other industrialized countries (United States, Canada, Japan, and some in Europe) took closer to 200 years to complete their demographic transitions. The remaining countries of the world began their demographic transitions only during the twentieth century, and did so much more suddenly, often going from high traditional mortality rates to low modern rates in a single generation. All countries in the world will eventually experience advances in sanitation and medical care, even if these are imported. The resulting reduction in death rates will bring about a demographic transition, even in the absence of economic development. The only exceptions may lie in countries where repeated famine and warfare (both positive checks) keep the death rates high.The United States may have completed a demographic transition a few years ago, when birth and death rates became approximately equal, a condition known as zero population growth. However, as we noted earlier, the U.S. population is once again increasing, and it remains to be seen whether the long-range trend will more closely resemble the zero growth phase or the more recent increase.Age structure of populations. The models we have examined so far treat all members of a population as being the same. However, we know that the probability of death and the probability of reproduction both vary with age. Thus, the true rate of population growth may vary depending upon the ages of individuals within the population. Grouping individuals by age gives the age structure of the population. The age structure can best be shown by a population pyramid, or age pyramid, such as those in Figure 9.6. Each horizontal layer on such a diagram represents the percentage of the population in a particular age group, with the youngest age groups on the bottom. Altogether, the age pyramid shows the distribution of individuals among the various age groups. To get a feeling for the scale of the age pyramids in Figure 9.6, notice that in Uganda the 0–4 age group constitutes about 20% of the population. Most age pyramids are divided by a vertical midline, with male age distribution shown on the left and female age distribution on the right. Notice in Figure 9.6 that the 0–4 age group has approximately equal numbers of males and females in all countries, but the 80+ age group has many more women than men in stable or declining populations. Among human populations, a pyramid with sloping sides and a wide base (many children) characterizes an expanding population. A shape maintaining more or less the same width throughout (except for the oldest few age classes) indicates a stable population. Astable age distribution is reached when the pyramid keeps the same shape as each age group grows older so that the numbers in each age group are replaced by an equal number advancing from the next younger group.Sometimes there are age bulges, as with the post World War II baby boom, when the birth rate increased temporarily. The United States and some other countries experienced a second baby boom (or a baby boom ‘echo’) in the late twentieth century as members of the earlier baby boom reached their prime childbearing years. In these countries, schools must now cope with the largest generation of school-age children that has ever lived.Predictions of future values of r can sometimes be made on the basis of age structure. Clearly, a population of 10,000 individuals with 4000 females of reproductive age has much more potential for increase than one with only 400 females of reproductive age. Calculations of the potential for future increase are often carried out by multiplying the number of females in each age group by the number of children that each of those females is likely to bear, then adding up these products for all age groups.Life expectancy. In most of the industrialized nations, the control of many infectious diseases since the late 1800s and improvements in sanitation have resulted in decreased infant mortality. A few twentieth-century changes, such as increases in smoking, auto accidents, and hand guns, have increased death rates, but these have generally been offset byFigure 9.6Age pyramids for two rapidly growing populations (high r), a population with a moderate rate of growth, two stable populations (r near zero), and a declining population (negative r), based on United Nations data for the year 2000. Age groups from 20 to 39 are darker to emphasize that most reproduction occurs in these age groups.age age ageURUGUAY80+75-7970-7465-6960-6480+75-7970-7465-6960-6480+75-7970-7465-6960-64malesfemalespercentage of population5percentage of populationpercentage of populationage age ageLATVIA80+75-7970-7465-6960-6455-5950-5445-4940-4435-3930-3425-2920-2415-1910-145-90-480+75-7970-7465-6960-6455-5950-5445-4940-4435-3930-3425-2920-2415-1910-145-90-480+75-7970-7465-6960-6455-5950-5445-4940-4435-3930-3425-2920-2415-1910-145-90-4malesfemalesr = –0.6110 5 05 1010 5 05 1010 5 05 10 percentage of populationpercentage of populationpercentage of populationmuch greater declines in the death rates from famines and infectious diseases. One consequence of declining death rates, especially among the young, is a greater life expectancy, meaning the average maximum age that people attain in life, or the age to which a person born in a particular place and at a particular time can expect to live (see the graph on our Web site, under Resources: Life expectancy). Life expectancy is calculated on a statistical basis, taking into account the probability at any age of a person’s proceeding on to the next age group. Therefore, both decreased mortality and increased longevity (the maximum age achieved by some individuals in the population) contribute to an increased life expectancy, with the largest increases resulting from reductions in childhood mortality. Life expectancy in the United States has risen from somewhere near 50 years in colonial times to over 75 years today, and the age group over 80 is the most rapidly growing segment of the U.S. population. This ‘graying’ of America and of many other countries results in a decrease in the proportion of the population in the most fertile age group and an increase in the proportion of older people, many of whom are dependent on the younger generation for their care. Numerous sociological changes follow the shift toward more people of advanced age and fewer children—more emphasis on medical care and less emphasis on schools, for example.Demographic momentum. Even after the birth rate falls to the level of the mortality rate, the population may continue to increase for another generation or two because of a demographic momentum. The momentum is caused by an age structure opposite to the one just described for a graying population. A population in which a large fraction of individuals is not yet of reproductive age (see Figure 9.6), while only a small fraction is past the age of reproduction, has a future reproductive capacity larger than one in which a higher percentage of the population is beyond reproductive age. Because the younger age groups are more likely to reproduce in the next 20 years and less likely to die, a temporary increase in the birth rate (and a temporary decrease in the death rate) can easily be predicted. The population will continue to grow until the age distribution readjusts itself more evenly, that is, until a stable age distribution is reached. With a stable age distribution, the birth and death rates will no longer change, unless some external factor disrupts the stable situation.World population estimates. Demographers estimate that the world’s population was about 50 million in 7000 B.C. and increased to about 250 million by the time of Christ. The earliest date for which there are reliable population estimates is 1650, at which time the world’s population stood at 500 million. By 1804, the world’s population stood at an estimated one billion. Adding the next billion took 123 years (to 1927), but the third billion was added in only 33 years (by 1960). The world’s population has increased even more rapidly since 1960, adding a fourth billion in only 14 years (by 1974), a fifth billion in 13 years (by 1987), and a sixth billion in just 12 years (by 1999) (see Figure 9.1).The United Nations has published tables with detailed predictions for the further growth of the world’s population under different sets of assumptions. According to the model that demographic experts consider most likely, the world’s population will grow to about 9.4 billion in 2050 and will stabilize at around 11 billion by the year 2200. Other models, with different sets of assumptions, predict population values in the year 2050 as low as 7.9 billion or as high as 10.9 billion. Each of theseassumes logistic growth, except for the model in which population growth continues exponentially at its present rate—that model predicts a population size of 296 billion in 2200, nearly 50 times the present value! Few, if any, biologists think that the latter is in any way sustainable; population growth will have to level off from its present rates.Because people do not generally find raising the death rate to be an acceptable method of lowering population growth, decreasing the birth rate is the only other option. In the next section we study reproductive biology and the factors that contribute to fertility. In the final section of the chapter we see how fertility can be controlled to lower the birth rate.THOUGHT QUESTIONSWhat changes (biological, social or economic) could increase the carrying capacity (K) of the entire world or of one nation? Should we be more interested in controlling r or in modifying K?Suppose that you count the number of people in a given town every year for 5 years and you discover that N hasstayed about the same during that time period; say, at 10,000. You also know that no one has moved into the town or away from the town in that time. What can you deduce about B and D? Confirm this for yourself by solving the equations given earlier in the chapter. Can you tell from this information how many people were born in the town in any of the 5 years?Study the age pyramids in Figure 9.6. Does the age distribution of the females or that of the males have a greater impact on future population size? Why?What values of r are typical during the several stages of a demographic transition? See Figure 9.5, and review the way in which r is defined.Which is likely to produce a greater increase in the number of people, a small population with a high r or a large population with a small r? Try some calculations with any values of N and r that you would like to examine. Use the simplest model that seems appropriate, then ask what changes the more complex models would bring.From the data presented in this chapter, can we estimate the value of K (thecarrying capacity) for the human population on planet Earth? Can wemake a minimum or maximum estimate? Have we already reached the carrying capacity of the planet?Which would you think would contribute more to an increase in life expectancy, decreased infant mortality or increased longevity?Among the ‘preventive checks,’ Malthus listed several forms of ‘vice,’ including the following:heterosexual intercourse outside marriage (“promiscuous intercourse”; “violations of the marriage bed”);sexual attraction to one’s own sex (homosexuality), to animals (zoophilia), or to inanimate objects (fetishism);“Improper arts to conceal the consequences of irregular connections” (i.e. birth control).Malthus listed all these practices as preventive checks. Which of them would actually function to limit population growth? Which might be interpreted as preventive checks under certain assumptions that Malthus might have made? Do you think these assumptions are realistic? Do you think Malthus condemned these practices because of their effects on population or because of his own moral views?What factors would need to be included in an equation to estimate what birth rate would produce zero population growth?Which countries currently have the highest population growth rates? Are they wealthy or poor? Are they influential?Where do they stand in the current world order?Human Reproductive Biology Helps Us to Understand Fertility and InfertilityIn sexual reproduction, a male haploid gamete unites with a female haploid gamete. The two types of gametes are produced by individuals of different sexes. We begin this section by comparing the anatomy and physiology of the two sexes in humans.Reproductive anatomy and physiologyReproductive anatomy includes those structures that allow for hormonal secretion, gamete production, sexual intercourse, gestation of the fetus, and nourishment of the young infant. Males and females differ in appearance and in the type of gamete that they produce. These differences result largely from the actions of hormones that are present in both sexes, but in differing amounts and with different consequences.Sex determination. The reproductive system, in the earliest stages of its development, is sexually indifferent, meaning that there are no indications as to the future sex of the embryo. The future gamete-producing reproductive organ (or gonad) is not yet male or female, but is just an indifferent gonad. As described in Chapter 2, several genes, including the SRY gene, begin to make products at this time. If the products of the genes SRY, SOX9, DMRT1, and DMRT2 are all present and functional, then the developing gonad becomes a male gonad or testis. The embryonic testis then begins to secrete the hormone testosterone and another hormone called APH (anti-paramesonephric hormone). In adulthood, the testis will also produce sperm. A developing gonad that does not become a testis becomes an ovary instead. The ovary will secrete the hormone estrogen throughout life, and will produce eggs during adulthood. The developing testis and its hormonal secretions are essential to the development of male internal and external reproductive structures, but the corresponding female structures develop without requiring estrogen. Thus, a genetic male with any of genes SOX9, DMRT1, or DMRT2 nonfunctional will develop a female phenotype, even in the presence of SRY. For this reason, embryologists say that the default sex of the embryo is female, and that male development can only occur when it is induced.Maturation and puberty. Hormones are small molecules that are used for chemical communication throughout the body. Beginning during embryonic development, the ovaries secrete estradiol (the major estrogen) and the testes secrete testosterone and APH. The reproductive organs are formed during embryonic development under these hormonal influences, but they remain immature until puberty. At puberty, a group of hormones produce many changes in the body. At an age that varies greatly around an average of about 12 years, increasing levels of the pituitary hormone FSH (follicle-stimulating hormone) stimulate the final maturation of the ovaries in females to begin producing eggs and the testes in males to begin producing sperm. These, in turn, step up their secretion of other hormones (estrogen and testosterone), stimulating (among other changes) the development of secondary sexual characteristics. Such characteristics include the widening of the hips, growth of breasts, and redistribution of body fat in females; the growth of facial hair and the deepening of the voice in males; and the growth of long bones and pubic hair in both sexes. The term ‘secondary sexual characteristics’ means that these features, while characteristic of mature men and women, do not have a direct role in the production of gametes.The age at which puberty occurs has declined steadily throughout the twentieth century in all countries in which such records have been kept. In Norway, which has kept records the longest, the average age at menarche (first menstruation) was just over 17 years in the 1840s but had declined to about 13.4 years by the 1950s. Data from other western European countries are consistent with this, and all countries show similar and steadily declining trends. One possible explanation is that puberty requires a critical weight (about 47 kg or 106 lb for females), and that improvements in childhood nutrition have allowed this critical weight to be achieved at earlier ages over successive decades. Consistent with this hypothesis is the trend in the United States over the past century, where a similar decline occurred, but where body weights have always tended to be above European averages. The average age at menarche has always been about 0.5–1.0 year younger in the United States than in western European countries, and is generally younger among African Americans than among U.S. whites. Beginning in the 1990s, this trend has begun to level off in many countries at an average age of between12.0 and 12.5 years at menarche.Male puberty is marked by the onset of sperm production (spermatogenesis). The pituitary hormone FSH initiates sperm production, and another pituitary hormone, luteinizing hormone (LH), induces other cells of the testis to secrete testosterone. Sperm production requires this testosterone for its completion, along with a small amount of estrogen. Female puberty is marked by the start of the menstrual cycle (see p. 299). After puberty, FSH, estrogen, and testosterone continue to have other roles throughout the lifetime of the individual. In males, some of the testosterone is converted into another hormone called DHT (dihydrotestosterone), and small amounts of estrogen seem to be essential for spermatogenesis and other processes. In females, FSH, estrogen, and progesterone are all important in the menstrual cycle, and small amounts of testosterone are thought to be important in generating thesexual appetite or libido.Male reproductive organs and sperm production. The sperm are male gametes, formed by the process of meiosis (see Chapter 2, pp. 42–44) in which each gamete receives half the adult number of chromosomes— one chromosome from each pair. Sperm have very little cytoplasm surrounding their nucleus, but they have a long tail that moves rapidly back and forth to propel the sperm along the reproductive tract of the female after intercourse (Figure 9.7).Sperm are produced in the testes of the male (Figure 9.8). The hormone testosterone is secreted by the interstitial cells that are crowded into the spaces between the sperm-producing tubules in the testes. (Testosterone is also made in smaller amounts by the brain in both sexes and by the ovaries in females.) The sperm accumulate in a series of wrinkled ducts that form the epididymis. The epididymis also secretes a fluid (the seminal fluid) that carries the sperm through a long duct called theFigure 9.7An egg surrounded by sperm. (B) Schematic diagram of a human sperm.vas deferens through which the sperm leave the testes. The left vas deferens and right vas deferens merge within the prostate gland, where they join the urethra carrying urine from the urinary bladder. The secretions of the prostate gland and the seminal vesicles add certain nutrients (including the sugar fructose) that help the sperm to swim more vigorously. Near the base of the penis, the bulbourethral gland helps squirt theseminal fluid and sperm throughthe length of the penis during ejac-(A)nucleus(B)headmiddle piecetailulation. Between ejaculations, sperm and seminal fluid are held in the ejaculatory ducts.Female reproductive organs and ovulation. The female reproductive organs (Figure 9.9) include the uterus and a pair of ovaries. The female gamete, or egg, is formed within the ovary by meiosis. The first meiotic division occurs before the egg is released from the ovary, but the second meiotic division, in which the chromosome number becomes haploid, is delayed until after the egg is fertilized. During the two cell divisions during meiosis in urinary bladder pubic bone prostate gland urethrapeniserectile tissueglans penis foreskinegg formation, the division of the cytoplasm between the offspring cells is extremely unequal. Only one of the four resultant cells becomes a mature egg with a large amount of cytoplasm to nourish the zygote after fertilization. The other three become polar bodies with very little cytoplasm, and these are usually lost. The nonreproductive cells surrounding the egg enlarge to form an ovarian follicle. The rupture of this follicle and the release of its egg are called ovulation.The menstrual cycle. Egg production and ovulation in mammals is a hormonally regulated cycle. In humans, this cycle lasts about 28 days and is called the menstrual cycle.The cycle of egg production and changes in the uterus is controlled by two ovarian hormones, estrogen and progesterone, and by two hormones (FSH and LH) secreted by the pituitary gland at the base of the brain (Figure 9.10). At the start of each cycle, which begins with menstruation, the pituitary secretes small amounts of FSH. The FSH stimulates two processes within the ovary: growth of an ovarian follicle, and production of the hormone estrogen, which reaches a peak concentration during the second week of the cycle. The estrogen stimulates the thickening of the lining of the uterus and the release of a second pituitary hormone, LH, that induces the release of the egg (ovulation), after which the tissue that surrounded the egg is left behind to form a scar tissue called the corpus luteum. The corpus luteum then grows. As it matures, it begins to secrete the hormone progesterone, which maintains the uterine lining in a thickened and receptive condition, ready for the implantation of an embryo should the egg be fertilized. If fertilization does not occur and no implantation takes place, the corpus luteum degenerates and the supply of progesterone drops sharply, causing the uterine lining to break down. The egg and the uterine lining are then sloughed off in the form of menstrual bleeding. The absence of progesterone also releases the pituitary to begin secreting FSH once again, initiating a new cycle.Figure 9.9The human female reproductive system.midline viewoviductovaryuterine walluterine cavityanterior view pubic bone urinary bladder urethraexternal reproductiveorgansclitoris labium minorlabium majorvaginaanuscervix rectumcervix vaginaFigure 9.10Reproductive cycles in the human female.During the menstrual cycle, changes in the concentration of each hormone stimulate the production of the next hormone in the sequence. Hormones from the ovaries and hormones from the pituitary regulate each other. In several cases, the presence of a later hormone has an inhibiting effect on the secretion of the previous hormone. This regulation of a previous step of a cycle by a later step of the cycle is called a feedback mechanism. In this instance, feedback prevents the overproduction of any hormone and stops the production of a hormone once ithas done its job.Fertilization and implantation. stimulates FSHstimulates LH & FSHbrainpituitarydaysNeither the sperm nor the egg live very long. After its release from the follicle, the egg travels along the uterine (Fallopian) tubes or oviducts, and it is here that the egg is fertilized if sperm are present.When the male ejaculates dur-0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 2 4 6ing sexual intercourse, approximately 300 million sperm are inserted into the vagina of the female. Of these, only about 3000 will successfully swim through the cervix and the uterus and into the oviducts, following hormonal signals released by the egg. Several sperm need to contact the egg to dissolve the coating that surrounds it. After the coating has dissolved, allowing a sperm to reach the plasma membrane of the egg, the sperm and egg plasma membranes fuse and the egg draws the sperm nucleus inside. The coating closes200100maturing follicleestrogenmenstrual flowovulationprogesteronecorpus luteum1050menstrual flowagain, preventing the entry of any more sperm nuclei. The egg completes its second meiotic division and its haploid chromosomes join with the haploid chromosomes from the sperm, a process called fertilization.If an egg is fertilized by a sperm, the resultant zygote continues travelling along the oviduct for 4–5 days, during which it undergoes several cell divisions and becomes an embryo. When it reaches the uterus, at a stage called the blastocyst, the embryo adheres to the inner (endometrial)0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 2 4 6dayslining of the uterine wall, a process called implantation (Figure 9.11).If the embryo does not implant, it does not develop further and is shed from the uterus. Implantation triggers the growth of the placenta, consisting of intertwined tissues of the embryo and the endometrium of the mother, through which the developing embryo is nourished (see also Figure 14.9, p. 531). Most of the organs of the growing embryo form during the first month, after which the embryo is known as a fetus.Impaired fertilityWe have described the normal events of human reproduction, in which egg and sperm from a fertile female and a fertile male combine to make an embryo. Not all individuals are fertile, however. A couple is usually considered infertile if they have been unable to get pregnant after a year of trying. Infertility can result from lack of production of sperm or eggs, low motility of sperm, shortened viability of egg or sperm, or anatomical abnormalities preventing the sperm from contacting the egg. A number of diseases, most of them rare, can cause permanent sterility. These include: several chromosomal anomalies and other genetic disorders; developmental anomalies of the reproductive system, including failure of the testes to descend; and some cancers, including those of the reproductive organs. Many sexually transmitted diseases such as gonorrhea and syphilis cause a loss of fertility that can be permanent (see Chapter 17). Many other infectious diseases can lower fertility temporarily, but the fertility returns to previous levels or nearly so once the disease is cured.A large number of other factors can also affect fertility in men and women. These are summarized in Table 9.2.A further factor is age. The most fertile years for both men and women are between the ages of 20 and 24. Many people choose to delay having children until later than that. After age 35, female fertility (the percentage of women who become pregnant when attempting to become pregnant) is less than half what it was at its maximum. The rate of spontaneous miscarriage is around 20% for women in their thirties, increasing to over 30% for women aged 40–44. Male fertility also decreases with age, gradually from age 40–55, and then more steeply after age 55.Since World War II, studies in various countries have documentedFigure 9.11Fertilization in the oviduct and implantation in the uterus.oviduct a general decline in male sperm counts and a rise in the number of sperm abnormalities. From 1938 to 1990, the average sperm count forday 4day 3day 2day 1European men declined to about half its former value, from 113 million to 66 million sperm per milliliter. Although the reasons are unclear, many researchers suspect that the cause may be related to an environmental presence of industrial chemicals and pesticides that have estrogen-like effects.uterusday 7 embryoinner mass of blastocystovaryblastocyst implantingfour cells two cellszygote fertilizationday 0In the next section we describe some of the methods that have been developed for overcoming infertility.muscle layeruterine wallsendometriumovulated eggTable 9.2Factors that can impair fertility.FACTOR DESCRIPTION OF EFFECTSHigh blood pressure and other circulatory A major cause of erectile dysfunction in men (failure of the penis to enlarge and stiffen during sexual disorders activity)Opiate drugs (including morphine, heroin) In women: loss of ovulation and of menstrual cyclesIn men: erectile dysfunction; loss of sexual interest (libido); low sperm countsAlcohol In women: suppresses ovulation and menstrual cycling (but the effect is inconsistent and affects different women to different degrees)In men: can lead to erectile dysfunction, loss of libido, sperm abnormalities, and a conversion of testosterone to estrogen that can lead to breast enlargement and sterilityTobacco Decreased fertility in both sexes; also earlier menopause in womenMarijuana In both sexes: decline in sexual desire; lowering of fertility; hormonal changes Also in men: breast enlargement; decreased sperm countCocaine (chronic use) In men: abnormal sperm and decreased sperm counts; erectile dysfunctionIn women: loss or disturbance of the menstrual cycles; also an 11-fold increase in uterine tube infertility Drugs used to control high blood pressure; In men: erectile dysfunction; decreased libido; inability to achieve orgasm or to ejaculatealso many antipsychotic drugs and (Inadequate study of women)antidepressantsMany anticancer drugs Inhibit both menstrual cycles and spermatogenesis; can lead to permanent sterility in both sexes Stress (probably acting by stimulating the In women: suppresses ovulation; loss or reduction of menstrual cyclesbody’s production of natural opiate-like In men: lowered sperm counts; decreased sperm mobility; increased sperm malformation; decreasedcompounds) testosterone levels; erectile dysfunction; loss of sexual interest (libido)Depression Loss of sexual activity and interestAnorexia; also physical overexertion, In women: loss of menstruation, failure to ovulate especially in female athletes and balletdancersHeavy metals (mercury, lead, etc.) Can cause permanent sterility in both sexesPolychlorinated biphenyls (PCBs), dioxin, Estrogen-like effects impair male fertility; males exposed to these chemicals before puberty have very many organic pesticides (including DDT) high rates of malformed internal and external reproductive structures including testicular disordersAssisted reproductionAt the population level, there are many motivations for decreasing the birth rate, but on an individual level the urge to have children is very strong. Many couples who cannot conceive a child seek help in becoming pregnant. Usually the first step is a complete medical assessment of both partners to see if a medical cause can be found; in approximately 20–30% of cases no cause can be identified. In parallel with research on birth control technologies, much research has gone into the development of several new technologies for assisted reproduction. Much of the research on infertility has been done in countries such as India and China, which also have active population control programs, a reminder that individuals and societies may have conflicting goals.If a couple remains infertile even after medical treatment, or if no medical treatment is appropriate, a variety of remedies can be suggested. In some cases, gametes from both partners are used to produce a child that is genetically theirs. In other cases, gametes are taken from one partner but not the other. Sperm donation is relatively easy and is more commonly practiced, but egg donation requires surgery and is thus less common. (Both sperm banks and egg banks have become profitable businesses in a number of countries.) A possibility always to be considered is adopting a child who is genetically unrelated to both parents.In this section we examine a number of options for assisted reproduction.Assisted gamete production. Various hormonal treatments are available to increase fertility in either men or women, for example by stimulating egg production and ovulation. Usually only one or a small number of eggs is released in a monthly cycle. Hormonal treatments for infertility may induce the release of many more eggs than normal and result in (fraternal, not identical) twins, triplets, and higher multiples if more than one egg is fertilized in the same ovulation cycle. The recent increase in the frequency of multiple births has been largely due to these treatments. (These treatments have no effect on the frequency of identical twins, which result from a fertilized embryo splitting.)Often these methods are used together with other forms of assisted reproduction. In males with low sperm counts, sperm may be harvested, then concentrated by centrifugation and used in the process of artificial insemination described next.Artificial insemination. Artificial insemination means introducing sperm into a female’s reproductive tract other than through sexual intercourse. The sperm could be derived from a woman’s husband or from another man. The procedure is fairly simple (and is routinely performed on cattle and certain other domesticated species, as are in vitro fertilization and surrogate pregnancy).However, the legal rights and responsibilities of a sperm donor other than the recipient’s husband are unclear in a number of jurisdictions.In vitro fertilization and embryo transfer. An in vitroFigure 9.12Outline of the procedure used for in vitro fertilization. process is one that takes place inlaboratory glassware rather than inside the body (in vivo). In the case ofin vitrofertilization, eggs are harvested from a woman (usually after hormonal treatment to stimulate egg development) and fertilized in a glass or plastic dish, using sperm contributed either by her husband or by another man (Figure 9.12). Fertilized eggs are then allowed to develop to approximately the 64-cell stage, after which one or more of these embryos are implanted in a woman’s uterus and allowed to develop to term. (The woman receiving the implanted embryo is usually the same woman who donated the eggs, but in some cases the recipient could be a surrogate.) Using sperm donated by some-stimulation of the ovarytransfer of blastocyst to uterusdevelopment of zygote to early blastocyst stagein vitro fertilization using donor spermretrieval of eggretrieved egg placed on culture medium one other than the woman’s husband raises the same kinds of legal issues (including custody and financial responsibility issues) as does artificial insemination.In vitro fertilization was first successfully practiced on humans in 1978 and is now used in over 36,000 cases annually in the United States and Canada alone. Several newer modifications of this technique are also occasionally practiced. In one such technique, called ZIFT (zygote intrafallopian transfer), the zygote is transferred soon after fertilization rather than waiting until the blastocyst stage. In GIFT (gamete intrafallopian transfer), the eggs and sperm are inserted into the uterine tubes and fertilization takes place there rather than in vitro. In cases of low sperm count or low sperm motility, sperm heads or whole sperm may be injected into egg cells instead of allowing fertilization to take place by itself.Persons who possess alleles that they do not wish to pass on to their offspring may seek in vitro fertilization and embryo testing before implantation, or artificial insemination using donated sperm. Genetic testing of the zygote or early embryo can be carried out before the use of any of the above techniques for implantation. Some researchers have been experimenting with techniques that test eight-cell embryos for genetic diseases (see Chapter 3). Because the testing process is usually destructive, only one of the eight cells is separated and tested, leaving the other seven cells available for implantation if desired; the organism resulting from a seven-cell embryo is just as normal as if all eight cells had been used. Embryos obtained by in vitro fertilization can thus be tested before they are implanted into a woman’s uterus to complete the pregnancy. This technique, sometimes called Blastomere Analysis Before Implantation (BABI) or Preimplantation Genetic Diagnosis (PGD), has already been used to test human embryos in vitro for cystic fibrosis, allowing the selection of only those embryos that are free of the disease. Selected embryos can then be implanted, and the couple can be free of the fear that their child will be born with cystic fibrosis, a disease that is usually fatal. Once this technique becomes readily available for a wider variety of human conditions, it will become possible to avoid certain genetic diseases by this procedure, or to choose certain other characteristics, such as the child’s sex.Surrogate pregnancy. Surrogate pregnancy is the use of another woman’s womb to carry a baby to term on behalf of a woman who cannot undergo the pregnancy herself, usually for medical reasons. In most cases, the baby is conceived by in vitro fertilization, if possible using egg and sperm cells donated by the couple who want the baby. The resulting embryo, which is the genetic offspring of the donor couple, is then implanted into another woman who agrees to act as a surrogate mother, usually for a fee. In addition, medical expenses are generally paid by the donor couple. The legal status and rights of the surrogate mother are subject to many ethical and legal questions. Surrogacy contracts have been outlawed or held invalid in a number of jurisdictions that view the birth mother (i.e. the surrogate) as the legal parent who is therefore ‘selling’ her baby if she receives any payment. Among the ethical issues raised are the exploitation of poor women by wealthy couples. Financial need is often a factor (one of many) in a woman’s decision to become a surrogate. Other issues include the amount of compensation that can ethically or legally be given to the surrogate and the ways in which this situation is distinguished from ‘baby-selling.’ A final issue concerns the available alternative of adoption, which is generally less expensive and raises fewer legal and ethical objections.The drive to reproduce is a strong force among all species, including humans. Not all humans want to have children, but for many it is something they desire greatly. When some people seek out assisted reproductive technologies to overcome infertility, it shows their motivation to have children that are genetically their own. In contrast, many people wish to limit the number of children that they have. In the next section we discuss the ways in which the timing and number of births can be controlled.Are there hormones that are found only in males? Only in females?Most forms of assisted reproduction are expensive and are likely to remain so, and success rates are generally low. They are considered elective procedures, and are therefore usually not covered by insurance.Is it discriminatory to provide assisted reproduction to those who can afford to pay for it, when so many other people cannot?Given the low success rate, should people be encouraged to give up after repeated failures? How many failures?Should an upper age limit be imposed on assisted reproduction? Should different limits be put according to age on the number of attempts at assisted reproduction?If an embryo is gestated in the uterus of a surrogate mother who did not contribute the egg, what rights should the surrogate have? What rights should the egg donor (and her partner) have? What legal rightsTHOUGHT QUESTIONSdo these parties have where you live? Should these parties have the right to negotiate and agree to a certain division of rights by contract? Why or why not?In most cases of assisted reproduction, multiple eggs are fertilized, only some of which are then implanted and brought to term. What should be done with the rest? If they are stored (usually in a frozen condition), who has the right to decide their fate? Does that include the right to destroy them, to refuse to pay for their continued storage, or to decide where to implant them? Can one member of a couple exercise any of these rights if the other member objects? What if the couple divorces or if their relationship changes inanother way?Do reproductive health clinics offer assisted reproductive technologies to couples who are infertile because of reversible lifestyle decisions (such as cocaine or marijuana use)? Do you think they should?Can We Diminish Population Growth and Its Impact?As Malthus realized, many factors influence population growth. Improving nutrition and health care generally increases population by increasing fertility, decreasing infant mortality, and decreasing the death rate.Deaths from accidents are being decreased by safety measures. To arrive at a stable population size without increasing the death rate, the main option available to people is a voluntary reduction of the birth rate.We should make note of a distinction at this point: population control is usually understood to operate on the level of populations, while birth control methods generally operate by preventing births one at a time. A birth control method is not a successful population control method unless it is widely adopted.Birth control is not new. It has always been practiced among human populations. Ancient texts in China, India, and Egypt mention abortifacients, i.e. drugs that induce abortions. In Egypt, the Ebers papyrus (1550 B.C.) describes a medicated tampon made with ground acacia seed. Fermentation of the seed in the female reproductive tract produces lactic acid, which is toxic to sperm. Many more birth control options are available today.Birth control methods work by controlling fertility, so the term ‘fertility control’ is often used as a synonym for birth control. Because these methods allow the spacing and timing of the birth of children, they are also called family planning methods. Many of these methods prevent pregnancy by interfering with the reproductive anatomy or physiology of either the female or her male partner. The various methods of birth control form a spectrum of possibilities (Figure 9.13). By the timing of their action, they can be arranged into four distinct groups, which are highlighted in the gray boxes in the figure.For each of the methods listed, a series of questions can be asked:How does it work?How effective is it in birth control?What costs or risks are involved?What kinds of objections have been raised against it?Does it have any benefits apart from birth control, e.g. in the prevention of sexually transmitted disease?Birth control acting before fertilizationOf all birth control methods, those that act to prevent pregnancy before fertilization (conception) are often called contraceptive measures.Preventing gamete release by sterilization. Sterilization, the elimination of reproductive capacity, usually involves surgery and is usually permanent, although some methods are potentially reversible. One way to achieve male sterilization and allow hormone secretion to continue is by vasectomy, the surgical cutting and tying off of the sperm duct (the vas deferens; see Figure 9.8). Males with vasectomies continue to produce both testicular hormones and sperm for some time, but the sperm cannot reach the penis for release.Among female sterilization methods, tubal ligation (tying off of the oviduct) is the only one done primarily as a birth control measure. Tubal ligation is analogous to male vasectomy; eggs and hormones are still produced, but the eggs are blocked from traveling to the uterus. Surgical removal of the uterus (hysterectomy) is performed for medical reasons other than birth control, but the removal of the uterus results in permanent sterility because the uterus is where the developing embryo grows.Surgical removal of the ovaries, the organs that produce the female gametes, also results in sterility, but this is usually avoided for the same reason as male castration is avoided: the gonads produce many hormones, and their removal has widespread effects on the individual.All these sterilization methods involve surgery, which makes them expensive to implement on a very large scale, especially in poor or medically underserved areas. As with all forms of surgery, there are risks, such as those of infection or from the use of anesthesia. However, both costsFigure 9.13Methods of birth control. effectiveness* relative cost to providehighhigh mediumII. PREVENTING FERTILIZATIONexperienced users 99.5%experienced users 99.5%experienced users 99%medium medium mediummediumnoneexperienced users 98%experienced users 84%experienced users 98%experienced users 98%experienced users 98%experienced users 98%experienced users 97%none nonenonelowlow mediumlowlowIII. PREVENTING IMPLANTATIONIV. INTERRUPTING GESTATIONexperienced users 98.5%medium mediumhighA 99% rate of effectiveness means that 1% of couples using that method will become pregnant in a year of use. and risks are experienced on a one-time basis only and do not recur. All sterilization methods are completely effective as birth control methods without any further action on the part of the individual.One of the greatest objections to all these methods is that they are permanent. Many people, even people who want birth control, do not want to become permanently sterile. In the United States, about 60% of men who undergo vasectomy later regret that they did so. Vasectomy and tubal ligation can in some cases be reversed, but success depends on microsurgical techniques, and reported success rates vary greatly. A new method for male sterilization has been developed in China, and is reversible under local anesthesia. In this method, a polyurethane elastomer is injected into the sperm duct, where it solidifies to form a plug that effectively blocks the passage of sperm.Preventing gamete release by hormonal methods. Several birth control methods depend upon alterations of the female reproductive cycle. Hormonal birth control methods take advantage of the feedback mechanisms shown in Figure 9.10. For example, estrogen and progesterone both inhibit the secretion of FSH, so that supplying these hormones (or a similar compound) prevents ovarian follicles from reaching maturity and releasing their eggs. The hormones can be given as birth control pills, as injections, as implants just under the skin, or as patches on the skin. Regardless of the method of drug delivery, all hormonal methods work by preventing the egg from maturing and being released. Because hormones have many effects throughout the body, hormones used in birth control have many side effects, including the possibility of blood clots. For this reason, medical supervision is recommended and hormonal methods require a prescription in most countries.Early birth control pills contained estrogen alone, but progesterone was later added (producing the combination birth control pills, also called ‘combination oral contraceptive’ or COC) to reduce the levels of estrogen and also its side effects. The continuous levels of these hormones prevent the usual hormonal cycling from taking place. The expense and the requirement of obtaining a prescription limit the use of birth control pills in many populations. Some developing countries have made birth control pills available without prescription, to encourage their more widespread use, but cost is still a problem. Birth control pills have become the most commonly used contraceptive method among the middle and upper classes in many countries. Most birth control pills sold today are of the combination type.Newer types of birth control pills, developed in the 1980s, use progesterone-like compounds (progestins) only. These include the ‘minipill’, which suppresses ovulation only half the time, but instead works primarily by thickening the cervical mucus. Minipills have a relatively high failure rate, largely because they need to be taken on time (even a 3-hour delay can reduce their effectiveness). For this reason, subdermal implants of progestins have been used in many cases. Implants of a drug called levonorgestrel (trade name Norplant) can be inserted beneath the skin in the underarm region, where they slowly release steady dosages of the drug. The early version, called Norplant I, quite commonly resulted in irregular menstrual bleeding, but this side effect is observed much less commonly with the newer version, Norplant II.Hormonal control of male fertility has been repeatedly suggested. One of the earliest such methods to be developed was a male contraceptive pill containing a drug called gossypol, derived from cottonseed. This drug was first developed around 1970 in China and is said to be about 99% effective. Although it does not affect the hormone testosterone, gossypol does somehow interfere with sperm production. Tests of gossypol have reported some toxic side effects, so an effort is now being made to develop a synthetic substitute.Testosterone is known to inhibit LH and FSH production by the pituitary, which in turn can inhibit sperm production. However, complete suppression of sperm production by this method requires weekly testosterone injections, and these injections may have undesired side effects. It has also been discovered that the suppression of pituitary function is actually brought about by the small fraction of the testosterone that is converted into estrogen. As a consequence, several researchers have begun exploring the possibility that estrogen or progesterone-like drugs might be capable of functioning as a male contraceptive. The drug Depoprovera, similar to progesterone, has been used for this purpose in Europe for several years, and in California it has been used to suppress testicular function in convicted rapists. (In this use, the drug does inhibit spermatogenesis, but it has no effect on violent behavior.)One of the newest proposed methods is the use of vaccines to achieve contraception by blocking reproductive hormones in males and thus inhibiting sperm production. In one approach being developed in India, men would be immunized against FSH, a hormone needed for sperm production; this method has been tested in animals and is now being tested in humans.Preventing gamete release by extended breast feeding. An older hormonal method of birth control is the practice of extended breast feeding (delayed weaning), which is common in many traditional societies in African countries. Children in Africa are almost always breast-fed, and many are not weaned until they are 4–6 years old. While a woman is breast feeding, she is producing hormones that stimulate milk production. These same hormones also inhibit the rise and fall of the hormones produced by the ovary, thus interrupting the menstrual cycle and preventing egg maturation. Women who use this method of birth control do not wean their youngest child from the breast until they feel they are ready to have another child. This method of birth spacing is a widespread and seemingly effective practice in many parts of Africa, although studies have shown that it is unreliable among women living in the industrialized world at high caloric intake levels. For example, prolonged breast feeding has a contraceptive effect among the !Kung San (Bushmen) of South Africa and Namibia. These women have a low caloric intake and walk 4–6 miles a day, conditions that seldom occur among North American women. Because the ability of breast feeding to delay the return of the menstrual cycle is greatest among women who are physically active but who have a low caloric intake, improvements in maternal nutrition may actually decrease the effectiveness of delayed weaning as a method of birth control. Birth spacing by prolonged breast feeding is also most effective when babies suck vigorously and often. Any contribution to infant nutrition other than breast milk (e.g., by bottled milk or cereal) reduces the effect. In most third-world countries, the use of bottled milk reduces the effectiveness of birth spacing by delayed weaning. The closer spacing of births leads to an increase in birth rates at the population level, possibly offsetting the effects of birth control programs. Even so, one expert states; “In developing countries today, breast-feeding probably prevents more births than modern contraceptive methods.”Preventing fertilization by sexual abstinence. As a means of preventing fertilization, abstinence has the distinct advantage of being available to all people free of charge. However, the success of abstinence methods depends upon the determination of the people using them. Total voluntary abstinence (celibacy) has long been practiced as part of a regimen of religious devotion, but only by small numbers of people. Delayed marriage (with no other sexual activity) greatly reduces the birth rate, especially inasmuch as the years before age 30 are the most fertile period for a majority of women.The so-called rhythm method is a form of partial abstinence, based upon the fact that a woman is fertile only for several days after ovulation, while the egg is in the oviduct or uterus; sexual intercourse performed at other times will generally not result in conception. Several versions of the rhythm method are practiced. The simplest version is a calendar method, in which a couple abstains from day 10 to day 17 (or, to be more certain, from day 7 to day 17) of a 28-day cycle in which the onset of menstrual bleeding is counted as day 1 (see Figure 9.10). Another version, with a higher success rate, is called the Billings method. In this method, the woman feels the mucus just inside her vagina with her fingers. Estrogen causes this mucus to become more slippery and elastic just before ovulation, when estrogen reaches a peak; after that, the secretion becomes scant and dry. A couple using this method abstains from intercourse from the onset of slippery mucus until 4 days after the peak day, but may have intercourse on the remaining dry days.If practiced correctly, the rhythm method is highly effective, but its effectiveness depends on several conditions, including the regularity of a woman’s menstrual cycles (this varies individually), the ability of the couple to keep a calendar and count the days without making a mistake, and the willingness of the couple to refrain from sex (or else to practice another method of birth control) during the woman’s fertile period. The effectiveness of the rhythm method can be increased by monitoring the woman’s vaginal temperature, since a rise in temperature indicates the time of ovulation more precisely.Sexual intercourse is also called coitus. Coitus interruptus is the withdrawal of the penis before ejaculation occurs. Some couples have used this method effectively, but the majority find it unsatisfying or difficult to follow. Since some sperm can be released before ejaculation, coitus interruptus is not reliable. On a population-wide scale, it is generally not as effective as other methods.Because of the high failure rates associated with abstinence methods, their advantage in low cost may be elusive. When the medical costs of an unwanted pregnancy are included, abstinence methods become among the most expensive methods available (Figure 9.14).Preventing fertilization by barrier methods. Barrier methods are those that impose a barrier to the passage of sperm. Most condoms aredesigned for males and cover the penis, but a condom that is worn by women has also been developed. The male condom is the oldest of the barrier methods. First developed in England, traditional condoms were constructed of animal membranes (usually sheep intestine) and were therefore considered a luxury item. The development of rubber and then latex made condoms more widely available and also more reliable. Condoms have the added advantage of protecting against AIDS and other sexually transmitted diseases (see Chapters 16 and 17).Other barrier methods include vaginal inserts (worn by women), such as cervical caps, vaginal diaphragms, and sponges. Vaginal diaphragms must initially be individually fitted by a physician or other trained medical worker, and must be inserted correctly into the vagina before intercourse and left in place for several hours thereafter. When properly placed, vaginal diaphragms block the movement of sperm from the vagina to the uterus, thereby preventing their joining with the egg. (One study in Brazil reported a higher-than-usual success rate if the diaphragm was left in place nearly all the time, but this result remains to be confirmed in other populations.) Cervical caps are made to fit over the narrow portion (cervix) of the uterus, where they also block sperm.Spermicidal agents, chemicals that can kill sperm, in creams, foams, jellies, or suppositories, are often used together with a barrier method; the combination of barrier plus spermicide is much more effective than either method used alone. One of the newest methods is a sponge impregnated with spermicidal fluid. (Spermicides should not, however, be used with many types of condoms; the spermicide partly dissolves the condom, making it ineffective as a barrier to sperm or to sexually transmitted diseases.)Barrier methods used with spermicides have extremely low failure rates when used by people familiar with their proper use; most pregnancies occurring with barrier methods are the result of improper use. Barrier methods are widely used in many countries.Birth control acting afterFigure 9.14Relative costs (over five years of use) of various birth control methods under the type of medical insurance plans common in the United States. For many methods, the largest costs are those associated with unwanted pregnancies resulting from the method’s failure. fertilizationSeveral birth control methods act after the egg has already been fertilized by a sperm.Preventing implantation. Hormones or hormone analogues can be used to prevent implantation of a fertilized egg if taken within 72 hours after intercourse. These postcoital or ‘morning-after’ pillscopper-T IUD vasectomy implant injectablesoral contraceptives progesterone-T IUDmale condom tubal ligation764$850$1290$1784$2042$2424$2584cost of method cost of side-effectscost of unintended pregnancy can thus be used for emergency contraception. Drugs of this kind contain either a high dose of estrogen or else a combination of estrogen and progesterone. In the United States, such drugs require a prescription, but emergency contraception kits containing these pills have been available in Europe for at least a decade, andwithdrawal ‘rhythm’ methoddiaphragm spermicides female condomsponge cervical cap$3278$3450$3666$4102$4872$5700$5730 school nurses in France can now dispense such drugs to teenage girls upon request.0 1 2 3 4 5 6total costs (thousands of dollars)One of the newest hormonal methods for preventing implantation is a drug called mifepristone (or RU-486), developed in France and now available elsewhere. In the United States, clinical testing found the drug safe and effective in preventing pregnancy. The drug was recommended for approval by the Food and Drug Administration (FDA), and is now legally available in the United States (with some restrictions) but is still not widely marketed, in part because of political pressure. Mifepristone blocks the action of the hormone progesterone, which is necessary for maintenance of a pregnancy. Mifepristone has its greatest potential use as a morning-after pill to prevent implantation from occurring during the first 5 days after intercourse.An intrauterine device (IUD) is a small piece of plastic or wire, in one of several shapes (e.g., coiled or T-shaped), that is inserted by a physician into a woman’s uterus, where it remains until removed by a physician. IUDs prevent pregnancy by preventing implantation, although the exact mechanism by which this occurs is not known. (Desert Bedouins have long practiced a similar method of birth control on their camels by inserting stones into the uteri of female camels to prevent pregnancy and removing the stone when breeding was again wanted.) A major advantage to this method is that, once inserted, the IUD works on its own with no need of further action on the part of the woman. On a worldwide basis, IUDs are used more than any other birth control method. This is largely due to the widespread use of IUDs in China, the world’s most populous country, and the method is widely used throughout Asia and Europe. In the United States, the use of IUDs trails far behind the use of birth control pills and even sterilizations. The steroid-releasing Progestasert and a version of the copper-T are the most-used IUDs in the United States.IUDs should not be used by women who have never been pregnant. However, women who use IUDs have a higher rate of satisfaction than with any other form of birth control, including pills. Today’s IUDs are effective and their failure rate is low. Earlier IUDs were not as safe; one early model, the Dalkon Shield, caused infections and severe bleeding problems in many women, resulting in hysterectomies, large lawsuits, and the corporate bankruptcy of its manufacturer. Many people have shown renewed interest in IUDs in the last decade because of the development of newer, safer types.Abortion. The termination of a pregnancy, including the cleaning out of the uterine lining and the expulsion of the embryo or fetus, is called abortion. The traditional method of dilation and curettage (enlarging the cervix, then scraping out the uterine interior with a spoonlike instrument) has now been supplemented by newer techniques such as vacuum aspiration (using a machine that uses suction to clean out the uterine contents). There are medical risks to the woman, including excessive bleeding, the chances of infection, and uterine injury, which can result in sterility. The sum total of risks to the life and health of the woman is less than the sum total of risks associated with completing the pregnancy and giving birth. The medical risks are especially low if the abortion is done early, during the first trimester, meaning the first 3-month portion of a 9- month pregnancy. Second-trimester abortions using saline injections can also be done safely in most cases. At whatever time an abortion is performed, the risks are much higher if it is done by an untrained person.Worldwide, the highest abortion rates are in the countries of the former Soviet Union, where other methods of birth control are not readily available. In 1990, an estimated 11% of all Russian women aged 15–44 had undergone an abortion. In contrast, The Netherlands has an abortion rate of less than 1%, one of the lowest among the countries for which data are available. Surveys have also identified The Netherlands as the country with the highest rate of virginity among women entering into their first marriage. Both of these findings have been attributed to a societal attitude that encourages open discussions of sexuality and sexual matters.The drug mifepristone, previously mentioned as a morning-after pill, can also be used to induce abortion after the embryo has become implanted in the uterus. Successful abortion has also been achieved in 96% of a group of 178 women given two drugs (methotrexate, followed days later by misoprostol) that are also legally available (by prescription) in the United States.Abortion is seldom considered as a method of choice. Even among people who have no ethical objections to its use, abortion is typically thought of as a last resort, to be used if an earlier-acting method fails in a particular case. Abortions performed by untrained persons carry a high risk of injury, subsequent infertility, or death. Safe abortions, performed by trained personnel under antiseptic conditions, are expensive. Most population planners have advocated that safe abortions be made a widely available option as a backup when the other, less costly methods have failed.Infanticide. Though not technically a means of birth control, infanticide has long been practiced as a means of population control in many parts of the world, especially in times of famine. There are records of infanticide from Medieval Europe, and the practice was still widespread in China, India, and other parts of Asia wellinto the twentieth century. In most cases, the infant is not directly killed, but is instead allowed to die through lack of care. In societies in which infanticide is practiced, female infanticide is more common than male infanticide. In China, infanticide is now officially outlawed, but boys outnumber girls in many areas. The government’s strict population control policy allows only one child per couple (Figure 9.15), and social scientists suspect that female infanticide is still widely practiced by couples who want a boy but instead have a girl.Cultural and ethical opposition to birth controlNo single method of population control is best for all societies. Abortions and sterilizations, for example, require medically trained personnel. They are more expensive and more laborintensive than other methods, and are therefore unlikely to become the methods mostFigure 9.15A poster promoting birth control in China. The poster reads, “birth control benefits the nation and benefits the people.” widely used even among populations that have no objections to them. All methods need to be adapted to the customs of the people using them, and education in the use of certain methods may meet with resistance of various kinds. For instance, women in many Muslim societies are generally forbidden to discuss reproductive matters with anybody outside their families, including health care workers.The attitudes of the Catholic church toward birth control have varied over the centuries; official opposition to most forms of birth control is historically recent. A considerable debate about birth control took place within the Catholic hierarchy in the 1960s, resulting in two Papal encyclicals, Populorum progressio (1967) and Humanae vitae (1968). The first of these acknowledges the population problem and the need for family planning in underdeveloped areas; the second denounces abortion, sterilization, and all forms of birth control except for the rhythm method. Surveys in many countries show that a large majority of Catholics use various forms of birth control despite the Church’s official position. Attempts to spread birth control information have often been opposed by the Church, especially in Latin America, but Church teachings have not stopped Italy, a country over 98% Catholic, from achieving a stable (nongrowing) population, with one of the lowest birth rates in Europe.Other religious groups have generally been more tolerant of contraceptive methods. Abortion, however, is opposed by Catholics, Protestant fundamentalists, Orthodox Jews, and Muslims. In its simplest terms, the principal argument voiced by these groups is that a fetus is a living human being and that killing it is an act of murder. People who wish to keep abortion legally available have argued several major points, including a woman’s right to choose, a child’s right to be wanted by his or her parents, and the need to control the world’s population. This is a highly charged issue.The abortion debate. Laws on abortion vary greatly from place to place and sometimes from one time period to another. In the United States, many states outlawed abortions until the Supreme Court ruling in Roe v. Wade (1973). As a result of this court opinion, women in the United States have a legally recognized right to an abortion under certain conditions. During the first trimester of pregnancy, this right can be exercised by the woman in consultation with her physician, without any interference from state laws. During the second trimester of pregnancy, state governments can impose waiting periods or certain other conditions, and during the third trimester they can limit abortions more strictly or outlaw them entirely. As a result, abortion practices vary from state to state. Practices also vary elsewhere: Ireland and most Moslem countries outlaw abortions, whereas most other European and Asian countries permit them.Many of the questions usually raised in the course of the abortion debate revolve around matters of definition: When does ‘life’ begin? Is a fetus a ‘person’? Is it a ‘human being’?Biological definitions of life. The usual definitions of ‘life’ (see Chapter 1,p. 11) mention properties such as cellular structure, motility, metabolism, homeostasis, the ability to respond to stimuli, and the presence of genetic material that is inherited. By these criteria, sperm cells, egg cells, and embryos are alive, and there is no age at which life begins. This, however, is a biological definition, and it still leaves for each society to decide the proper treatment, ethical status, and legal rights of human embryos. A “pro-life” advocate could use this definition to argue that abortion is a form of murder, whereas an advocate for reproductive choice could just as well argue that organs that are ‘alive’ by this definition are routinely removed surgically and discarded as ‘medical waste,’ and that an abortion is in this regard the moral equivalent of an appendectomy.There are many other possible criteria for defining the start of human life, including the following.Anything that possesses human genetic material (DNA) could be considered human, so an embryo would be considered human throughout its development. Also human by this definition are human gametes (haploid sperm and egg cells) and the ‘medical waste’ such as human blood and surgically removed organs and tissues.A new individual could be defined to begin its life when it attains a unique individual genotype at the moment of fertilization.An embryo could be defined as a new and distinct individual once it loses the ability to split into separate individuals with separate personalities and experiences, at approximately 12 days after implantation.An embryo could be defined as a separate person only when it is capable of surviving outside the womb. This ability depends to a great extent on the ability of the lungs to remain open and function in aerating the blood. Only after the 25ºBy the end of the week, the lungs are sufficiently well perfused with blood vessels for the baby's tissues to receive enough oxygen. before 25º week, the lungs tend to collapse when empty, and their internal mucous linings tend to stick together, preventing the lung from refilling. Many states in the United States use this criterion to define the legal status of a fetus as ‘viable,’ and therefore the killing of the fetus as an act of murder from this age forward.If life ceases when brain waves (EEGs) can no longer be detected, then the beginning of sentient life could be defined by the onset of these brain waves, at about 26–27 weeks of gestation. In their book, The Facts of Life (New York, Oxford University Press, 1992), Harold Morowitz and James Trefil argue for an ‘acquisition of humanness’ (and independent viability) at the time when most of the connections between nerve cells in the cerebral cortex are made. Electrical waves in the brain (EEGs) (see Chapter 13, pp. 494–495) begin at about this time, providing evidence that the fetus can now respond to certain stimuli and can be described as having ‘experiences.’A baby could be defined as alive when its circulatory, respiratory, and digestive systems begin to function independently of its mother. These changes occur at birth, when the umbilical cord is cut and the baby takes its first breath.Each of these definitions could be used to argue for a particular legal or ethical treatment of human embryos, but ultimately this is a social, ethical, and legal decision rather than a biological one. In fact, different societies (and sometimes different legal jurisdictions) use these criteria very differently.Legal definitions of personhood. ‘Personhood’ is a social or legal concept, not a biological one, and it is differently defined in each culture or legal system. In the legal system followed in the English-speaking world, a ‘person’ is defined as a legal entity having certain legally recognized rights and duties. In this tradition, corporations and estates have the legal rights of ‘persons.’ The ‘personhood’ of a fetus is therefore a matter of legal definition and not of biology, and, because legislators can define personhood in various ways, the legal rights of a fetus can vary from one jurisdiction to another. Other cultures have their own ways of defining the rights or personhood of a fetus or newborn:in Japanese tradition, a baby is not considered a person until it utters its first cry, so killing it is not considered homicide;in parts of West Africa, a child is not considered human until it is a week old;the Ayatal aborigines of Formosa had no punishment for killing a child before it was given a name at age two or three years;natives of the Pacific island of Truk considered deformed infants to be ghosts and either burned or drowned them.The point is that different cultures and different legal systems can reach remarkably different conclusions. Notice again that these are really not scientific questions, capable of being decided entirely by observational data.Ethical considerations. Using the ethical principles discussed in Chapter 1, a deontologist who opposed abortions would simply argue that it is a wrongful act regardless of any type of medical or other evidence. Such a person would regard the matter as totally outside the bounds of science, because no possible observation or experimental evidence could change the wrongness of what they regard as a wrongful act. A utilitarian would weigh the possible consequences of an abortion (including the monetary costs and the medical risks) against the consequences of the birth if carried to term. Among the latter consequences are medical risks to the mother’s health from the delivery, medical expenses, and the costs to the mother of raising the child (or the costs to society, if for some reason the mother does not raise the child properly). From a utilitarian viewpoint, the mother’s wishes, abilities, and financial circumstances are all important in the evaluation; to the deontologist, they are all irrelevant. Much of the frustration of the whole abortion debate is that deontologists and utilitarians talk in such different terms and use such different arguments that neither has much hope of convincing the other of anything.In the meantime, a small number of anti-abortion extremists have resorted to bombing clinics, and terrorizing or shooting doctors who perform abortions. Many hospitals have discontinued performing abortions to avoid being the targets of such intimidation. One result is the increasing concentration of abortions performed at clinics that do little else, making them easier targets for these extremists. Other results are that fewer doctors are being trained to perform abortions, while many other doctors who might otherwise perform abortions are refusing to do so for reasons of personal safety. These developments further reduce the pool of doctors and hospitals willing to help someone seeking an abortion. In some states it has become increasingly difficult for a woman seeking an abortion to find a doctor willing to perform one.Population control movementsOrganizations to promote birth control and control population growth were first formed in the nineteenth century. In England, several of these organizations called themselves ‘Malthusian,’ even though Malthus, a curate in the Anglican Church, was opposed to nearly all of the birth control methods available in his day. Knowledge about reproduction and birth control was not widely available before the mid-twentieth century. An 1832 book on the subject by an American physician, Charles Knowlton, was banned as immoral in the United States and elsewhere. Two British reformers, Charles Bradlaugh and Annie Besant, and an American, Margaret Sanger, worked through the late 1800s and early 1900s to make information and contraceptives more widely available. Besant strongly influenced Mahatma Gandhi and later migrated to India. Sanger always viewed birth control from the perspective of giving individual women more control over their own lives. The availability of birth control in the United States owes much to her tireless campaigns. She also traveled widely, spreading the message of birth control to India, China, and Japan. The influence of Gandhi, Besant, and Sanger led India to become the first modern nation to institute a government-funded campaign to control its population. Beginning in 1951, India implemented population control measures that featured easy access to both contraception and abortion and an information campaign to encourage their widespread voluntary use. During the 1960s, nine other nations, including China,Egypt, and Pakistan, also implemented population control programs.The most ambitious population control program in history was adopted in China in 1962, at a time when their population was around 700 million and was growing at just above a 2% annual rate. The campaign for “only one child for one family” (see Figure 9.15) was waged with special vigor. Parents who had only one child were given various benefits (such as pregnancy expenses paid for the first child only, free contraceptives, better housing, and educational benefits), while parents who bore more than one child were fined and sometimes imprisoned. The goal of this campaign was not just to limit population growth, but to reduce the population to its 1962 level of 700 million as quickly as possible. Because of a large demographic momentum (that is, an age structure with many children), China’s officials realized that they would have to cut the birth rate to somewhat below the mortality rate for a time in order to achieve a stable population. China’s population in 2000 was around 1.3 billion, but the annual growth rate has been cut to 0.71%.The education of womenOne of the most effective methods of reducing the number of children borne by each woman is to educate women. Studies in many parts of the world have shown that the population birth rate falls with each rise in the education level of women, even in the absence of any program aimed specifically at birth control (Figure 9.16). Around the world, the countries with the lowest rates of female literacy also have the highestFigure 9.16The education of women reduces the average number of children per family. Data for the graph are from the World Bank.population growth rates, whereas those with higher female literacy have lower growth rates. Countries with female literacy rates below 15% include Yemen, Niger, and Burkina Faso, all with population growth rates of 3.0% or more. Third-world countries with female literacy rates of 80% or higher include Jamaica, Sri Lanka, Lesotho, Botswana, and Tajikistan, all with population growth rates below 1.0%.Third-world women with a seventh-grade education or higher tend to marry later than other women (4 years later, on average, and these are among the most fertile years). They also use voluntary means of birth control more often, have fewer (and healthier) children, and suffer far less often from either maternal or infant mortality in childbirth. The empowering of women (by giving them more education and more control over their reproductive lives) also raises the educational level of their children and results in more rapid economic development (at lower cost) than many other programs aimed more specifically at development.In the United States, educational efforts are also an important part of most efforts to reduce pregnancy rates in teenagers. The rate of teenage pregnancy is lowest among women with the most years of schooling and highest among those with only a grade-school education or less.Although most population control programs are carried out by national governments on their own populations, several programs are international in scope, including those run by the World Health Organization (a branch of the United Nations) and by the U.S. Agency for International Development (USAID). The United Nations has sponsored many conferences on population. Some past conferences emphasized the environmental impacts of population growth, but the 1994 conference in Cairo, Egypt, shifted the attention to the education of women. Women’s rights advocates from a variety of countries stressed the need to improve both the education and legal status of women. Many people cautioned that overzealous government-sponsored programs aimed at population control could restrict the reproductive freedom of individual women as much as the earlier lack of birth control information. Although theseMore education, fewer children76543210Teenage women in a Papua New Guinea classroomLatin AmericaAfrica Asiaeducation of mother: no schooling4—6 years of schooling7 or more years of schooling people generally see the need to reduce the rate of population growth, they are deeply suspicious of programs that coerce individual women or restrict their freedom, and they are especially suspicious of programs urged upon third-world nations by male-dominated institutions in the industrial world. Instead, they favor programs to educate women and improve their legal status and reproductive choices. They point out that birth rates have diminished whenever the education, legal rights, and reproductive choices of women have improved.Controlling population impactDemographic transition brings about a marked increase in human population. In most parts of the world, the excess population tends to migrate to the cities, producing an overcrowding that strains the resources of those urban areas. In Europe and Japan, this process occurred gradually over a period of several hundred years (roughly, 1600 to 1900), giving cities a chance to adjust to their changing conditions. Many cities have accommodated high population densities (meaning large numbers of people per square mile) without widespread misery. Since World War II, urbanization in the third world has taken place much more rapidly than it did in Europe. Rapid, unplanned growth has strained most urban services to the point at which many of the newly arrived migrants have inadequate housing. Crowded slum areas or shanty towns often lack safe drinking water and may also suffer from chronic water shortage; sanitation and waste disposal are also frequent problems. It is often not crowding in itself that results in these problems, but crowding without sufficient facilities to support the population. Crime often increases and may become difficult to control, although many other factors beside population contribute to crime rates. Unemployment and economic hardship, when they occur, may compound these problems. The hardships of urban crowding usually fall disproportionately on the poor.Pollution (see Chapter 19) tends to increase approximately in proportion to population, most obviously because of corresponding increases in household garbage and waste water. Densely populated areas are dependent on food, water and fuel coming in from a much wider radius; consequently their environmental impact is felt far beyond their political borders. As population increases, more forests are cleared for agricultural use and more trees are cut down to build houses. The destruction of habitat for other organisms, particularly of forests, is one result (see Chapter 18). The loss of arable land (through topsoil erosion, desertification, and other processes) is accelerated by population growth, as is the depletion of nonrenewable resources such as minerals or fossil fuels.Effects of consumption patterns. The impact on the environment is not, however, solely a function of the number of people. The amount of the world’s resources that each person consumes is not equal around the globe. On average, the amount of resources consumed by a person in the United States is 54 times that consumed by a person in a developing country. The impact of this consumption is magnified still further by the fact that much of this consumption is of nonrenewable resources. In addition, resources that might be renewable are often consumed or discarded in ways that make them nonrenewable. The enormous size of municipal solid waste disposal sites in industrialized countries is testament to these consumption patterns. These landfills are among the largest structures ever built by humans, and the materials within them are unavailable for reuse or biodegradation.If the rate of energy use does not exceed the rate at which energy is captured from the sun in photosynthesis (see Chapter 11), then the energy use is considered sustainable. In many industrialized countries, however, present patterns of energy consumption are already unsustainable because they remove far more energy from global ecosystems than they produce.Discussions of the world’s population crisis frequently become linked to discussions of the environmental crisis. Many people, especially in the third world, believe that the population crisis is only a small part of a greater environmental crisis.This environmental crisis, they say, is made worse by the industrial world’s overconsumption more than by the third world’s population increase. Frances Moore Lappé is one of several American writers holding such views. Some analysts even question whether the industrial world’s concerns over population are misdirected (and possibly racist). Third-world countries, they say, could well support far larger populations than they do now if it were not for the export of so many of their resources to support the patterns of overconsumption that have become so typical of the industrial world. If the industrial countries, they say, were to give up their lavish patterns of consumption, then the third world could well support a larger human population (at a larger carrying capacity) than it does in current circumstances.Others take what may be called a neo-Malthusian position. Paul Ehrlich, for example, views most other problems as consequences of overpopulation. If the population were smaller, he argues, most environmental problems would diminish or even disappear. Because some countries (mostly in Europe) have already limited their population growth, the greatest efforts should be directed at those nations (mostly in the third world; see Figure 9.2) that have the highest population growth rates.Overpopulation and overconsumption need not be viewed as opposing viewpoints. Population growth and profligate consumption are both widely recognized as problems, and each makes the other worse. Some people see one of these as the bigger problem; some people see the other. Efforts directed at addressing either problem can only help to ameliorate both.Limits on carrying capacity. Many scientists tell us that we will soon reach or even exceed the carrying capacity of the planet. In fact, this is one point on which people concerned with overpopulation and those concerned with overconsumption agree, although they postulate different causes for this condition. One of the few dissenters, economist Julian Simon, observes that the technological revolutions of past centuries have repeatedly brought about demographic shifts, each of which has increased the carrying capacity. He predicts that future technological revolutions will continue to enlarge the planet’s carrying capacity indefinitely. Nearly all other scientists and writers who have contemplated the subject of population believe instead that the planet’s carrying capacity has a limit.Can the global carrying capacity be increased further? The answer is not known with certainty, but it depends in part on whether we assume the Earth’s natural resources to be renewable and unlimited (Julian Simon’s view) or limited and nonrenewable (the majority viewpoint). Those who accept the limits imposed by nonrenewable resources will be driven to the conclusion that carrying capacity cannot be increased very much. In fact, if we maintain our present patterns of consumption, we may not even be able to sustain the present population levels forever.Human populations, like all other populations, are biological entities, requiring energy flow to survive. Populations are therefore subject to the laws of physics (energy is neither created nor destroyed), and populations cannot exceed the limits imposed by the availability of energy. When they approach K, populations are controlled by biological factors, such as starvation and disease. So the question “Should populations be controlled?” is academic because populations will be controlled by the forces of biology and physics, regardless of our answer. The relevant questions are, “Should we exercise preventive efforts at population control?” and, if we should, “How should we do so?”Is an increase in population the only factor that puts resources in limited supply? Does population growth affect the availability of housing or medical care in the same way that it affects the availability of drinking water, sanitation controls, and food?Find out whether your college makes birth control information and birth control itself available to the student population. Are certain methods favored over others? Why?Why are most forms of birth control aimed at women rather than men? Why are most population control campaigns aimed at women? In societies in which women have little or no control over their lives, are they likely to be able to carry out family planning? Will family planning give them greater control?Do you think it is proper to view birth control information as a freedom-ofspeech issue? Do you think birth control methods should be taught in the public schools? Why or why not?What social benefits are likely if population growth is controlled? What social and ethical problems need to be considered? What individual rights are at risk? In your opinion, what is the best wayTHOUGHT QUESTIONSfor a government to control its country’s population growth without restricting the reproductive freedom of its women?In what countries is abortion legal? Where is abortion illegal? Can you suggest reasons for these differences?Can biology have any useful role in the abortion debate? What role? Would any biological data be persuasive to a person who opposed abortion on the basis of deontological principles? Would data be persuasive to someone using utilitarian ethics?Most stem cells (useful in cancer research or cancer therapies) come from discarded embryos and aborted fetuses. Fertilized eggs are the ultimate stem cells. However,U.S. law prohibits the National Institutes of Health (NIH) from funding any experiments that deliberately create or destroy a human embryo. How does this restriction on research relate to the abortion debate in the United States? Do you agree with the restriction? If you do not, how would you change the law?In Practice Question 15 on p. 324, what considerations have been ignored? Do you think they may safely be ignored?Concluding RemarksIndividual decision making in family planning is sometimes at odds with government decisions aimed at population control and also sometimes with various religious teachings. There are also many other reasons why people might resent strangers urging them to modify their most personal behaviors in one way or another. All of these factors, moreover, vary from place to place, and the lessons learned in one country or population cannot necessarily be applied uncritically to other populations elsewhere. However, any attempts to implement change based on biological data will necessarily take place in a context of many, often competing, social values. Many scientists think that moving to sustainable consumption levels may partly alleviate the problems of population growth, but only temporarily. In addition, motivating people to decrease their consumption may be just as difficult as motivating them to have fewer children. Even well-planned efforts to address social, economic, or environmental problems may prove to be inadequate as resources are stretched to the breaking point in the face of increasing population pressure. “Whatever your cause,” says one slogan, “it’s a lost cause unless we can control population.”Chapter SummaryThe principles of population ecology are applicable to all species.A new population shows rapid exponential growth at first, but its growth rate ® levels off when it approaches the carrying capacity (K) of its environment, a phenomenon called logistic growth.The effects of population growth beyond the carrying capacity are numerous: consumption of resources is increased, pollution is increased, and any inefficiency in the utilization of resources results in starvation and death.Humans and otherK-selected species are characterized by stable populations at or near carrying capacity (K) and by most individuals living a long time. In contrast,r-selected species show more rapid growth, higher mortality early in life, and unstable population sizes.Human populations have grown markedly after each major advance in technology. Each major population increase has taken the form of a demographic transition, beginning with declining mortality and ending when the birth rate (B) declines to match the death rate (D).Many factors promote infertility, including those that interfere with the menstrual cycle in females or with sperm quality in males.Ovulation and many other aspects of sexual development and of fertility are controlled by hormones.Understanding reproductive biology can help us to treat infertility and also to control the birth rate.Many methods of birth control are available. They differ in their biological mechanisms, their costs, their medical risks, and their acceptance by different groups of people.Summary to Chapter 9 323Many studies have found that improvements in the education and legal status of women lowers the birth rate in a cost-effective manner and brings other benefits besides.PRACTICE QUESTIONSWhat is the birth rate B in a nation with 4 million men and 3.9 million women, in which 200,000 children are born in one year? What is the birth rate B in a nation with 3 million men and 4.9 million women, in which 200,000 children are born in one year?What is the death rate D in a nation of 100 million people in which 500,000 people died in a year and 200,000 of those who died were children below the age of 2 years? What is the death rate D in a nation of 100 million people in which 500,000 people died in a year and 50,000 of those who died were children below the age of 2 years?What is the growth rate r in a nation of 500 million people if the birth rate is 2% and the death rate is 1% (assuming no immigration or emigration)? What is the growth rate r in a nation of 50 million people if the birth rate is 2% and the death rate is 1% (assuming no immigration or emigration)?How many people will be added in one year to a population of 500 million people with a growth rate of 2%? How many will be added if the growth rate is 4%? How many will be added at growth rates of 2% or 4% if the initial population was 5 billion?What is the doubling time of a population of 500 million people if the growth rate is 2%? What is the doubling time of a population of 5 billion people if the growth rate is 2%?If a population is at its carrying capacity K of 500 million and its birth rate is 3%, what is its death rate (assuming no immigration or emigration)? If a population is at its carrying capacity K of 5 billion and its birth rate is 3%, what is its death rate (again assuming no immigration or emigration)?A population of 4.5 million has a birth rate of 0.067 (or 6.7%) and a death rate of 0.024 (2.4%). Find thegrowth rate ® and the number of years that it will take for the population to double.For the population in the previous question, find:the population increase this year;the size of the population after a year of increase;the population increase in the second year;the population size after 2 years of increase.Which will increase more rapidly this year: a population of 3.3 million with a growth rate of r = 2.0%, or a population of 5 million with a growth rate of 1.1%?Where in the body is testosterone produced? Where in the body is estrogen produced?During the menstrual cycle, what hormones are secreted by the ovaries? Other hormones are involved, in addition to the ovarian hormones. Where in the body are these other hormones produced?How do hormonal contraceptive methods induce infertility?How do barrier contraceptives prevent fertilization?A particular birth control method is 98% effective. In a nation of 8 million people, if 400,000 women use this method, how many of them will become pregnant this year?Suppose you are working for a family-planning program in a nation whose population is growing rapidly. Among several available methods of birth control are the following.Method A costs $1600 per woman, lasts an average of 20 years, and is 99% effective.Method B costs $20 per month for each woman and is 78% effective.Method C costs $200 per year for each woman and is 88% effective.Which method is most cost-effective (reduces pregnancies by the largest amount per $1000 spent)? (See also Thought Question 9 on p. 321.)IssuesDo all humans have the same dietary requirements?How are human diets related to good health?How are they related to chronic diseases?What is malnutrition? What are its causes and consequences?What social factors contribute to obesity or heart disease?Why do some people deliberately starve themselves?Organ systems (digestive system, circulatory system)Cell membranes (diffusion, active transport)
acid
Molecular structure (chemical and physical fundamentals of biology: water, carbohydrates, lipids, proteins, enzymes, polar and nonpolar molecules) Energy and metabolism (energy conversion and storage, chemical binding energy, ATP, calories, glycolysis, energy cycle, Krebs, oxidation-reduction). reactions) Evolution (lactose intolerance)
homeostasis
Health and disease (macronutrient malnutrition, micronutrient malnutrition, dietary fiber, eating disorders, ecological factors) Interspecies interactions (mutualism) for energy Chemical and mechanical processes in digestion The digestive system Conversion of macronutrients into cellular energy Ingested nutrients circulate throughout the body Circulatory system The HeartCardiovascular diseaseMalnutrition contributes to poor healthIncreasing eating disorders in developed nationsHungerEnvironmental factors contributing to malnutritionImpact of poverty and the war on healthMicronutrient malnutrition10325326Nutrition and healthAt 65kg, Melanie considered herself fat and ugly. Her menstruation stopped when her weight dropped to 100 pounds (45 kg). Now that she weighs 40 kg all her friends say that she is too skinny but she is sure that they are wrong because she still thinks that she is chubby. She wants to lose more weight. Melanie has an eating disorder called anorexia nervosa. Your body is not getting the nutrients it needs. She can die if the situation is not treated. Melanie's father came in for a routine checkup last week. Although he was fine, the doctor said he had high blood pressure and needed to monitor her fat intake. If he doesn't reduce the fat content of her diet, she is at greater risk of having a heart attack. She must now learn to eat a diet low in fat and high in fiber, which reduces her chances of developing heart disease, the leading cause of death in most developed countries. We all need food, but our nutritional needs vary based on our height, age, gender, activity level, and previous health status. In addition, there are variations caused by hereditary differences in body constitution, metabolic rates, and other factors. The world's population has found many different ways to meet these nutritional needs. Different diets have emerged in different parts of the world because different types of plants thrive best in different climates and soil types, and each culture has its own preferences and do's that restrict the use of foods available in its environment; No culture uses all the food available, standing up for them. In this chapter, we examine the body's use of food, human nutritional needs, the correlations of diet with the incidence of chronic disease, and the impact of malnutrition that can result from undernourishment or malnutrition. Malnutrition is one of the biggest health problems in the world, especially among the poor and in crisis areas. Malnutrition can also be the result of disordered eating in people with adequate access to good food. All people have nutritional needs for good health is a need for energy measured in kilocalories (kcal). A kilocalorie is the amount of energy needed to heat one kilogram of water by one degree Celsius. The "calories" that dieters count are actually kilocalories. Your body's caloric needs depend on many factors, including: B. Body weight, activity level, and gender (Table 10.1). A completely inactive person (say, in a hospital bed) needs a minimum amount of calories, and this amount can be converted into a basal metabolic rate, the rate at which an inactive person uses energy. Caloric intake is the most important measure of nutritional adequacy. In most industrialized countries, most people are well or overfed. In developed countries, especially the United States, many people are overweight. A large number of obese people (and some who are not) have attempted to modify their food intake through diet, either to lose weight or out of an increased interest in health. In general, a diet is the sum of all foods consumed by a person or population. Popularly, "dieting" means something more restrictive: making conscious food choices to achieve the desired result. Diets that lead to weight loss do so by reducing calorie intake. Other diets, such as "heart-healthy" diets, aim to promote long-term health by excluding or including certain types of foods. However, diets can be taken to the extreme and a diet that is seriously unbalanced from a nutritional point of view can be detrimental. Inadequate caloric intake is the most common nutritional problem worldwide. Hunger kills millions of people each year, most of them children. Hunger and malnutrition are most evident in non-industrialized or third world countries, but also in impoverished areas, both rural and urban, in many industrialized nations. In malnourished people, there are many other nutritional problems, such as: B. vitamin deficiency; Most of these other problems are difficult to treat if caloric intake remains inadequate. Most of what we call food can be chemically divided into three types of main components and various secondary components. The main components, called macronutrients, include carbohydrates, proteins, and lipids (fats); Minor components, called micronutrients, include vitamins and minerals. Food is used to fuel all life activities and macronutrients are the main sources of energy. In addition, the human being needs fiber and micronutrients, which are not sources of energy but have other vital functions. We then examine the biology of these food components to understand why a balanced diet is necessary to maintain good health. We also see the consequences of increasing or decreasing the intake of certain foods. Carbohydrates Most people around the world get most of their calories from carbohydrates, which include starches and sugars. Plants store energy in the form of carbohydrates, making them a good dietary source of carbohydrates. Grains such as wheat, rice, oats, and corn are the most nutritious source of carbohydrates because they also contain important vitamins, protein, and fiber. Bread, pasta, and other foods made from grains retain all their nutritional value as long as the whole grain is used. Fruit and fruit-based products (including juices) often contain sugars such as fructose or sucrose, as well as important vitamins, minerals, and fiber. However, refined sucrose (table sugar) lacks these other nutrients and can also contribute to dental caries (Box 10.1). Most vegetables contain carbohydrates, but they are even more important as sources of vitamins, minerals, and fiber. Carbohydrates are molecules composed primarily of three types of atoms: carbon, hydrogen, and oxygen (Figure 10.1). A single carbohydrate unit is called a monosaccharide or simple sugar. Simple sugars differ in the number of carbon atoms and in the arrangement of their chemical bonds. More complex carbohydrates are built by connecting these monosaccharides in pairs (disaccharides) or larger structures (polysaccharides). Starch is a common polysaccharide made up of repeating units of the sugar glucose (see Figure 10.1). Carbohydrates are largely soluble in carbohydrates and in water due to an important similarity in the types of bonds. In a chemical bond, two atoms are held together by sharing electrons between the two atoms. These bonds can be polar or nonpolar (Figure 10.2). Polar bonds have an uneven distribution of electrons, and therefore electrical charge, while nonpolar bonds have a much more uniform electrical charge distribution. water (H)2O) is one of the most polar liquids with electrons unevenly distributed between the hydrogen and oxygen atoms. Carbohydrates have many polar bonds between the hydrogen and oxygen atoms and also between the carbon and oxygen atoms. Due to the high proportion of oxygen atoms and polar bonds (see Figure 10.1), carbohydrates tend to be soluble in water. The daily carbohydrate requirement of the human body is measured as total caloric intake, as shown in Table 10.1. BOX 10.1 How does sugar contribute to cavities? The sugar we add to coffee or cereal is chemically known as sucrose. There are many other sugars: fructose (fruit sugar), lactose (milk sugar) and dextrose (synonymous with glucose). Many bacteria live in our mouths and use these dietary sugars for their metabolic power. One type of oral bacteria produces a glue-like substance that sticks to the surface of the tooth, and to produce this substance, they need sucrose. Once the bacteria attach to the tooth, they can use other sugars (including sorbitol, the sugar in "sugarless gum") for energy. When bacteria extract energy from sugar, acids are produced, and these acids dissolve tooth enamel, leading to cavities. Without sucrose, bacteria cannot make glue and acids cannot adhere to the enamel surface either. 4 kilocalories per gram (kcal/g). From an energy standpoint, it makes little difference whether the carbohydrates are consumed in the form of sugar or starch or whether the sugar is fructose or sucrose. However, there is a difference in the speed of absorption: starches usually take a few hours to break down into absorbable sugars, while dietary sugars can be absorbed in minutes. A meal that contains both sugar and starch therefore keeps the body's energy (or blood sugar) levels more constant for a longer period of time. In most populations, it is desirable to increase the consumption of carbohydrate-rich foods (especially whole grains). Figure 10.1 Chemical structure of selected carbohydrates. SIMPLE SUGARS – MONOSACCHARIDES COMPLEX SUGARS – POLYSACCHARIDES Glucose (blood sugar) Fructose (fruit sugar) Starch (multiple sugars). of glucose molecules connected in branched chains and TWO SUGARS - DISACCHARIDES lactose (milk sugar) glucose molecule cellulose (polysaccharide of glucose molecules connected in linear unbranched chains found in plants) glucose molecule glycogen (polysaccharide of glucose molecules connected in branching chains and found in animal cells) Hydrogen atoms Oxygen atoms (form polar groups) Carbon atoms (form nonpolar groups) Sucrose (table sugar) Glucose molecule Less kilocalories of work or fewer dollars to produce a kilocalorie of carbohydrates than a kilocalorie of most foods high in fat or protein. In the United States, replacing dietary fats with complex carbohydrates, particularly from whole grain sources, would have many indirect health benefits, including a reduced risk of heart attacks and certain cancers. Lipids Lipids are organic compounds that do not dissolve in water because they consist mainly of hydrogen and carbon atoms arranged in nonpolar hydrocarbon chains. Common lipids are fats, oils, waxes, phospholipids, and steroids. Dietary lipids are primarily triglycerides, molecules in which glycerol (a three-carbon molecule) is linked to three long chains of carbon and hydrogen called fatty acids (Figure 10.3). Triglycerides that are solid at room temperature are commonly called fats; those that are liquid at room temperature are commonly known as oils. As caloric sources of energy, fats and oils contain almost 9 kcal/g, more than double that of carbohydrates. A small amount of lipids is a dietary necessity, in part because fat-soluble vitamins (particularly A and D) cannot be absorbed without them. Lipids are also a source of fatty acids, which are the nonpolar portion of the phospholipid molecules that make up cell membranes. Two specific fatty acids (linoleic and arachidonic acids) are needed from dietary sources because the body cannot make them, but they are needed in very small amounts (about 3 g or one tablespoon per person per day). Most people who are not starving have an adequate intake of lipids. In the United States, many people eat too much fat. The body tends to store excess lipids (and some excess carbohydrates) as fat depots in numerous adipocyte cells (fat storage). Fatty acids, cholesterol and cell membranes. Saturated fats are fats whose fatty acids have only single bonds (see Figure 10.3). Most saturated fats come from animal sources (or some tropical plants like palms and coconuts), and most are solid at room temperature. Unsaturated fats, often of plant origin, have double and single bonds in their fatty acid chains, causing the molecule to double (see Figure 10.3). Those that contain only one double bond are sometimes called monounsaturated; those with multiple double bonds are polyunsaturated. Both types are generally liquid at room temperature because the bends in the double bonds prevent the molecules from sticking together too closely and becoming solid. Fats are important for cell membranes. Fatty acids from dietary fats are incorporated into cell membranes as part of molecules called phospholipids. As we have seen, the fatty acid portion is nonpolar, but the other end of a phospholipid is polar. In water, phospholipids ++ orient water (H2O):a polar molecule with unequally shared electronsa fatty acid: a nonpolar molecule held together by nonpolar bonds spontaneously to form bilayer membranes in which the phospholipid polar heads face the watery surfaces and the nonpolar fatty acid tails are protected from the water by forming the interior of the bilayer (Figure 10.4). Membrane proteins are embedded in this phospholipid bilayer.Cells remove the fatty acid chains from dietary triglycerides and incorporate the chains into membrane phospholipids. When unsaturated fatty acids are incorporated into the phospholipid cell membrane, the bends prevent their tight packing in the membrane, keeping the membrane more fluid. The phospholipid molecules need to be fluid to allow the embedded proteins to function. Conversely, if the diet is high in saturated fats, the membrane is less fluid, which reduces the functioning of membrane proteins such as those involved in nutrient absorption into cells. It is hypothesized that when dietary lipids cannot be properly absorbed into cells they may tend to build up on blood vessel walls, contributing to heart disease.Another important dietary lipid is cholesterol, a fat-soluble molecule that is an important constituent of animal cell membranes (see Figure 10.3, and notice the absence of chains in the chemical structure). Along with unsaturated fatty acids, cholesterol helps to keep the membranes fluid, thereby keeping the cell and the organism functioning properly. Cholesterol is also the precursor of several important hormones.Figure 10.4The structure of phospholipids and cell membranes. The cell membrane shown is an animal cell membrane, and therefore contains cholesterol.Structure of a phospholipid moleculeWe need cholesterol in small quantities, but our bodies can usually synthesize this amount, so little or none is needed from food. Plant cell membranes do not contain cholesterol, so plant products are always cholesterol-free, although some (like coconut oil) contain saturated fatty acids that are easily converted into cholesterol by the body. All dietary fatty acids are broken down into one of the major starting materials of cholesterol synthesis; cholesterol synthesis is thus increased by nearly all fatty foods, even if they are advertised as ‘cholesterol free.’Because the body makes about 75–80% of its own cholesterol, and makes it from dietary fats, most of the cholesterol circulating in the bloodstream comes from dietary fats (especially saturated fats), not from dietary cholesterol. Excess cholesterol, like excess amounts of other lipids, can build up on blood vessel walls and increase your risk of disease. Most foods that contain cholesterol are also high in saturated fats, so avoiding either also helps you to avoid the other. Eggs are exceptional polar headN in having a lot of cholesterol with few other fats.Closeup of the phospholipid bilayerPOUTSIDE THE CELL– – – – – polar– O O H H O O H H OO H H H H + + H H + + Hwater molecules regionH + + + ++ + + fatty acid tails (non-phospholipid bilayer+ – ––– – – – –– – –polar endnonpolar endphospholipid moleculephospholipid molecule polar)– – – – –+– – –+– – –+ +cholesterol (nonpolar)+ + H+ + H H +HwaterH + H OHO H H O OH O moleculesO H–General structure of the plasma membrane– – – – –INSIDE THE CELL surface carbohydrateOUTSIDE THE CELLmembrane proteins polar regionnonpolar regionlayer of phospholipid molecules phospholipid bilayerINSIDE THE CELLcholesteroltransmembrane channel proteinProteinsThe body uses proteins for tissue growth and repair, including the healing of wounds, replacement of skin and mucous membranes, and manufacture of antibodies (see Chapter 15). Proteins are important components of all cell membranes and can function to transport other molecules across cell membranes or as receptor molecules. Many proteins of the cellular interior provide structure, motility, and contractility to muscles and other cells. Other proteins such as collagen and elastin are located outside cells and give connective tissues their strength and thus help to support the entire body. Keratin, another protein found outside cells, is essential for healthy skin and is the main constituent of hair and fingernails. A much larger assortment of proteins function as enzymes, as described later in this chapter. Some enzymes (such as those used in digestion) function outside cells (extracellularly); many others function inside cells (intracellularly).Some body proteins are needed only in small quantities, but our muscles, blood, skin, and connective tissues need proteins in large amounts. Tendons and certain other body parts are made of proteins that are relatively stable once they have been formed, but blood, skin, bone tissue, bone marrow, and many internal membrane surfaces all undergo constant reworking, repair, and replacement, requiring new protein supplies throughout life. Protein requirements are even higher, per unit of body weight, in growing infants and children, in pregnant or lactating women, and in persons recovering from a major illness or injury.Dietary amino acids. Proteins are built from chains of smaller chemicals called amino acids. The digestive system breaks down the proteins in food into individual amino acids. After they have been absorbed by the body, these amino acids can then be used to build the body’s own proteins. How a protein functions depends to a large extent on its threedimensional shape after the linear sequence of amino acids has folded. The way in which a protein folds, and whether it is stable in the watery cytoplasm of the cell or in the nonpolar cell membrane, is determined by the arrangement of the polar and nonpolar side groups of its amino acids (Figure 10.5).Because proteins are synthesized by adding one amino acid at a time to the end of a growing chain (see Chapter 3, pp. 66–67), if one type of amino acid is missing from the cell, the synthesis of any protein needing that amino acid stops. An amino acid that is present in small quantities and is used up before other amino acids is called a limiting amino acid. Proteins are necessary in the diet. The daily requirement is 0.8 g per kilogram of body weight, for example, about 45 g for a 125-pound (57 kg) woman, or 64 g for a 175-pound (80 kg) man. Each species has its own capacities for making certain of the amino acids and therefore has its own dietary requirements for those it cannot make. Of the 20 standard amino acids, 8 cannot be synthesized by the human body and are therefore considered essential in the human diet; a ninth amino acid is essential in human infants. The human body can make the remaining aminoacids from these ‘essential’ amino acids.Complete and incomplete proteins. Most animal proteins arecomplete proteins in that they contain all the amino acids essential inFigure 10.5Chemical structure of part of a protein.nitrogen atoms hydrogen atoms oxygen atoms carbon atomsthe human diet. Soy protein is also complete, but most plant proteins lack at least one essential amino acid needed by humans. When an incomplete protein is eaten, the body uses all the amino acids until one of them, the limiting amino acid, becomes depleted. After the limiting amino acid is used up, the body uses the remaining amino acids to produce energy instead of making proteins, because dietary protein cannot be stored for later use in the way that carbohydrates and lipids can.To get around the problem of incomplete plant proteins in the human diet, we can eat them in combinations in which one plant protein supplies an essential amino acid missing in another one. The Iroquois and many other Native Americans commonly obtained complete protein by combining beans, squash, and corn in their diets. Most bean proteins, for example, are deficient in the amino acids valine, cysteine, and methionine, while corn proteins are deficient in the amino acids lysine and tryptophan. Alone, neither one of these proteins is nutritionally complete for humans, but in combination (as in corn tortillas with a bean filling, or succotash, a mixture of beans and corn cooked together) the two plant sources provide a nutritionally complete assortment of amino acids because each has the essential amino acids that the other lacks.Vegetarian diets. The amino acid inadequacy of plant proteins poses special problems for vegetarian (meat-avoiding) diets. Vegetarian dietsA tripeptide of three amino acids held together by peptide bonds (red lines)are generally rich in carbohydrates, fiber, vitamins, and more amino acidsamino acid 1side group 1amino acid 2side group 2peptide bond peptide bondamino acid 3more amino acidsside group 3minerals, but they may be deficient in certain amino acids unless care is taken to combine several plant proteins at once. Some vegetarians avoid meat but consume fish or milk or eggs; these ‘ovolacto vegetarians’ can usually meet their protein needs without much difficulty, especially if they combine proteins from both plant and animal sources in the same meal. the breaking of the peptide bonds releases the individual amino acidsStrict vegetarians, also called vegans, who do not eat food from any animal sourceH H O N C CH O HHH H O N C CH O HCH2(including milk or eggs), need to carefully combine plant proteins sources so as to supply their bodies with nutritionally complete protein. For example, legumes (beans, peas, and peanuts) can be combined with whole grains (such as rice, corn, or wheat).Glycine has the simplest side group, ahydrogen atom.Seven amino acids have side groups that are insoluble in water. Phenylalanineis such an amino acid.Nine amino acids have side groups thatare soluble in water. Cysteine is such an amino acid.Nuts and seeds contain protein and can be used to supplement amino acids missing from plant proteins fromother sources. Some vegetables also contain individual amino acids that can serve the same function. Our Web site contains vegetarian recipes (under Resources: Vegetarian) and additional references.Because animal cells store energy principally as fat, proteins obtained from animals are accompanied by fat. Plant cells, in contrast, store energy in the form of complex carbohydrates such as starch, and plant proteins are thus accompanied by very little fat.Plant-rich diets have other advantages. A given amount of arable land can support a larger human population if that land is used for raising crops for human consumption, including sources of plant proteins, than if the same land is used to raise food for animals that humans can eat. It takes 5–16 pounds of grain protein to produce one pound of meat protein. In well-fed countries with plenty of land, such as Australia or the United States, large tracts can be used for grazing or for the raising of crops primarily for animal consumption. However, poor countries of high population density can ill afford to feed crops to animals. Most of the world’s poor eat little meat and get most of their protein from vegetable sources, or in some cases from fish. All whole-grain cereals contain some protein. If this protein is eaten with beans or other legumes, a high-quality protein source is created that is much less expensive than meat and contains far less saturated fat.The consequences of inadequate protein intake are discussed in a later section.FiberNot all nutrients are required as sources of calories. One example is fiber, material that the body cannot digest and absorb. Human diets should include both soluble fiber (pectin, gums, mucilages) and insoluble fiber (mostly cellulose), and both types are present in most fruits, vegetables, legumes, and whole grains. Many of these fibers are complex carbohydrate molecules, of which cellulose (see Figure 10.1) is an example. An increase in dietary fiber reduces the incidence of several cancers, especially those of the intestine, but scientists are not sure about the exact mechanism of this effect. One intriguing possibility is that protection against these cancers depends on the rate of movement of food through the intestine, and that fiber maintains the optimal rate of food movement. Higher rates cleanse the intestine of potentially toxic chemicals, while lower rates allow these chemicals to remain in one place long enough to undergo fermentation by bacteria into cancer-causing substances (carcinogens; see Chapter 12). Another possibility is that harmful carcinogens are frequently present inside the intestine for whatever reason, but a mucous secretion protects the intestinal lining from them; the insoluble fiber rubbing against the intestinal lining stimulates the lining to secrete more of this protective mucus.Soluble fiber such as oat bran may reduce the level of serum cholesterol and the risk of heart disease. The mechanism for this effect is not known with certainty, but one hypothesis is that certain soluble fibers bind strongly to bile, synthesized from cholesterol and secreted into the intestinal tract to aid in fat digestion. Without the soluble fiber, the bile would be reabsorbed by the intestinal lining and reused, but the soluble fiber prevents this reabsorption and ensures that the bile is eliminated with the stools. Without recycled bile, new bile must be synthesized from cholesterol, which the body withdraws from the blood, lowering blood cholesterol levels. Diets that are high in fiber are statistically associated with lower rates of coronary heart disease and stroke.VitaminsPlants are good sources of micronutrients—vitamins and minerals— because plants need these substances and use them for their own metabolism.Vitamins are complex nutrients needed only in very small quantities. Most vitamins are coenzymes, the nonprotein portions of enzymes needed for the enzymes to function as catalysts (see p. 343). Enzymes (and their coenzymes) are needed only in very small quantities because they are used and reused in the chemical reactions that they regulate. There are over a dozen vitamins categorized into two groups—water-soluble and fat-soluble (Table 10.2). They may be obtained either from pills or from food. The reasons for preferring vitamins in food are as follows.They are much less expensive this way.Foods rich in vitamins are also rich in other important substances, including minerals, fiber, and protein, nutrients that have other important health benefits. We do not know the complete nutritional requirements of any organism more complex than bacteria, and undoubtedly our food contains many unknown but needed nutrients. These other nutrients, known and unknown, are not obtained from vitamin pills.Some vitamins are more easily absorbed by the body in the combinations with other ingredients that exist in food than they are in the combinations that exist in vitamin pills.Purified vitamins can be toxic if taken in excessive amounts, an unlikely danger with vitamins contained in foods.Vitamin overdoses and deficiencies. The amounts of vitamins recommended for maintaining good health are called recommended dietary allowances (RDAs). Most of these amounts are the same for most healthy adults, but menstruation, pregnancy, and lactation can alter some values in women. Nutritional requirements also differ for growing children and for people recovering from a major illness or injury.Either too much or too little of a vitamin can result in disease. Vitamin overdoses are possible, but are more likely with fat-soluble vitamins. Water-soluble vitamins, including vitamin C and the B group of vitamins, do not accumulate in the body. When you eat more than you need, the excess is simply excreted in the urine. They must therefore be taken in regularly. Because they are not stored, these vitamins cannot easily build up to toxic overdoses, especially if you get them from foods. It is, however, possible to overdose on water-soluble B vitamins taken in pill form or as concentrated liquids, particularly vitamin B6. Vitamin B6(pyridoxine) is a coenzyme for many of the enzymes involved in the synthesis of amino acids; Therefore, it helps build protein and is sometimes used by bodybuilders. Daily doses of 500 mg or more can be dangerously toxic to the nervous system and liver. The fat-soluble vitamins, namely A, D, E, and K (see Table 10.2), accumulate in the body's adipose tissue and can accumulate over time. Overdoses of these vitamins, especially vitamins A and D, can be toxic. Vitamin deficiencies may be more common (worldwide, but not as common in industrialized countries). Fat absorption disorders often lead to a lack of fat-soluble vitamins, as these vitamins are transported and absorbed along with dietary fat. People with such disorders may have many vitamins in their blood, but their cells cannot absorb them. The disease results from a deficiency in any of the vitamins; In fact, research into the cause of these diseases led to the discovery of vitamins.Vitamin B1. Vitamin B1(Thiamine) was the first vitamin to be chemically characterized. When Dutch physician Christiaan Eijkman was stationed on the island of Java in the 1890s, he noted that polyneuritis, a neurological condition that affected chickens, had many symptoms similar to a human disease called beriberi. Both illnesses caused muscle weakness and paralysis of his legs, making it impossible for him to stand upright; both diseases were Table 10.2 Vitamins and minerals in human health. IMPORTANCE FOR GOOD HEALTH GOOD FOOD SOURCE WATER SOLUBLE VITAMINS Vitamin B1(Thiamin) Helps break down pyruvate; keeps meats, whole grains, vegetables, nerves, muscles, and blood vessels healthy; prevents beriberiVitamin B2(Riboflavin) Important in wound healing and carbohydrate metabolism of yeast, liver, kidney; Prevents dry skin, nose, mouth and tongue Vitamin B3(Niacin) Maintains healthy nerves and skin; prevents pellagra Legumes, fish, whole grains Vitamin B6(pyridoxine) coenzyme used in the metabolism of amino acids; prevents whole grains (except rice), yeast, liver, mackerel, microcytic anemia avocado, banana, meat, vegetables, eggs, vitamin B12(cyanocobalamin) Required for DNA synthesis and cell division; prevents meat, liver, eggs, dairy products, whole grains pernicious anemia (incomplete development of red blood cells) Folic acid Used in the synthesis of hemoglobin, DNA and RNA; prevents asparagus, liver, kidney, fresh greens, greens, megaloblastic anemia and spina bifida yeast2Egg, Liver, Tomato, YeastVitamin C (Ascorbic Acid) Antioxidant; used in the synthesis of collagen (in connective fresh fruits (especially citrus fruits and strawberries), fresh tissues) and epinephrine (in nerve cells); promotes the healing of vegetable wounds, liver, raw meat; protects the mucous membranes; prevents scurvy FAT SOLUBLE VITAMINS Vitamin A (retinol) antioxidant; visual pigment precursors; prevents night yellow and dark green vegetables, some fruits, fish blindness and xerophthalmia Oils, creamy dairy products Vitamin D (calciferol) Promotes calcium absorption and bone formation; prevents eggs, liver, fish, cheese, clarified butter and osteomalacia antioxidant vitamin E (tocopherol); protects cell membranes from organic whole grains, nuts, legumes, vegetable oils, peroxides; maintains reproductive health Vitamin K Essential for blood clotting; prevents bleeding Green leafy vegetables MINERALS Electrolytes (Na+, K+, Cl–) Maintains fluid balance in the body; raisins, prunes; K+ also in membrane potentials of dates Calcium is part of the crystalline structure of bones and teeth; receive dairy products, peas, canned fish with bones, muscles and nerve membranes (sardines, salmon), vegetables phosphorus component of the crystalline structure of bones and teeth dairy products, corn, broccoli, peas, potatoes, plums magnesium preserves muscles and membranes nervous meat, milk, fish, green vegetables iron part of hemoglobin; used in reactions that produce energy Meat, egg yolks, whole grains, legumes, vegetables Iodine Helps thyroid gland; prevents goiter Fish and other shellfish Fluoride strengthens the crystalline structure of tooth enamel Drinking water, tea Zinc promotes bone growth and wound healing Seafood, meat, dairy, whole grain products, eggs liver collagen, capillary elastin, and selenium Statistically associated with lower death rates from heart disease from vegetables, meat, grains, shellfish, stroke, and deadly cancer when persistent. Eijkman observed that chickens only developed polyneuritis when fed polished white rice, but the disease cleared up when rice bran was added to the feed or when brown rice was used. Thiamine was later isolated from the bran or husk of unpolished rice grains (Figure 10.6) and has been shown to be effective in both the treatment and prevention of beriberi in humans. Since thiamine is a vital (necessary) substance and also an amine (a chemical that contains a -NH2group) was called a "vitamin". Subsequently, this term was shortened to "vitamin", and then to "vitamin", and the name was applied to the entire class of substances that are needed only in small quantities. Thus, Eijkman's discovery led to the concept of vitamins, for which he received the Nobel Prize in 1929. Beriberi occurs primarily in people whose dietary carbohydrates come from a single, highly refined source, such as white rice or white flour. (not fortified). Many countries now have laws that require the addition of thiamine (and other B vitamins) to refined flour. For this reason, beriberi is rare in developed countries today, although it occurs in heavy alcoholics whose food intake is inadequate. Other B vitamins. Other water-soluble vitamins are described in Table 10.2. Many vitamins owe their discovery to research into diseases such as beriberi (so-called vitamin deficiency diseases). Vitamin B6Deficiency (microcytic anemia) is common in people whose diet consists mainly of rice. Lack of niacin (vitamin B3) causes pellagra, a disease of the skin and nervous system. The body can make its own niacin from the amino acid tryptophan, which is found in many proteins. But populations where corn is the only source of protein are often at risk of pellagra because corn is particularly deficient in available niacin and tryptophan. Corn kernels are produced through a process that makes tryptophan (and therefore niacin) available from the corn protein. Vitamin C. Lack of vitamin C causes scurvy, a disease once common among sailors at sea and among prisoners. A 17th century British naval surgeon discovered that lemons and other fresh fruits prevented and cured scurvy. Then British ships began carrying limes and it became so notorious for the practice that British sailors were nicknamed "limeys" due to the severity of the symptoms of said infection, but for that reason it cannot be considered a "cure" or prevention. of a common disease. illness. cold to be considered, as is sometimes claimed. People who take large doses of vitamin C may experience scurvy symptoms when they stop taking the vitamin. In addition, megadoses can induce hemolytic anemia (red blood cell deficiency caused by the breakdown of red blood cells) in people with G6PD metabolic deficiency (see Chapter 7, p. 233) found in African American, Asian, and Sephardic Jewish populations . Additionally, people with a genetic predisposition to gout find that high doses of vitamin C can sometimes trigger the condition by raising uric acid levels in the blood. Megadoses of vitamin C can cause deficiencies in another vitamin, the B12in people with iron deficiency. Even in healthy people, megadoses of vitamin C can irritate the intestines enough to cause diarrhea. Antioxidant vitamins. Vitamin A (retinol) is important for the synthesis of light-sensitive (retinal) chemicals used in vision. Vitamin A is also an antioxidant, which means that it protects the body's tissues from chemicals that would steal electrons from those tissues. The removal of electrons from any molecule is a process chemists call oxidation. Oxidizing agents are chemicals that cause oxidation by absorbing electrons; Among the most reactive oxidizing agents is a group of chemicals called free radicals, which have one or more unpaired electrons and a strong tendency to remove electrons from other molecules. Therefore, free radicals can damage many cellular molecules and are thought to play a role in the initiation of some types of cancer (see Chapter 12). Free radicals are present in many things, including cigarette smoke, car exhaust, and meat grilled over an open fire. Vitamin A and other antioxidants protect the body by destroying free radicals. Vitamin A can be obtained from animal sources such as dairy products or fish. Many vegetables also contain a vitamin A precursor, the yellow-orange beta-carotene, which is broken down after eating to produce two vitamin A molecules. High consumption of beta-carotene-rich whole foods is statistically associated with lower rates of lung cancer, but the causal relationship between the two is unclear. Laboratory studies of beta-carotene, primarily in rodents, have shown that it suppresses or retards the growth of chemically induced skin, breast, bladder, esophageal, pancreatic, and colon cancers. Vitamin E (tocopherol) is another antioxidant vitamin that is particularly important in breaking down a group of strong oxidizing agents called peroxides. Vitamin E also helps prevent miscarriages and stillbirths in pregnant rats and for this reason has earned a reputation as an anti-sterility vitamin. However, health claims about the effects of this vitamin on sexual function remain unproven. Vitamin E overdose leads to low blood sugar and headaches, fatigue, blurred vision, muscle weakness, intestinal disorders, and higher rates of lung diseases such as emphysema. Vitamin E comes in several forms, the most potent being alpha-tocopherol. It is destroyed by both freezing and cooking. Other fat soluble vitamins. Vitamin D (calciferol) is discussed in more detail in Chapter 7 (pp. 239-241). It is important for the body's use of calcium in bone formation. Vitamin K is essential for blood coagulation as it acts as a cofactor in the reactions that produce blood coagulation factors from their inactive precursors. Most people get adequate amounts of vitamin K from the bacteria that live in their intestines. However, newborns whose gut bacteria have not yet colonized and people whose gut bacteria have been killed by antibiotics require more vitamin K from food until the gut bacteria become established or re-established. Minerals Minerals are inorganic (not carbonaceous). ) ions and atoms necessary for proper physiological function. Sodium (Na+), potassium (K+) and chloride (Cl-) ions are the main electrolytes (charged particles) in the body. Differences in the concentration of ions on opposite sides of a cell membrane are both a type of concentration gradient and a type of electrical gradient, collectively called the membrane potential. Like chemical bonds, membrane potentials are a means by which cells store energy in a usable form. An example of a membrane potential is the electrical potential of nerve cell membranes (Chapter 13, pp. 467-468), which arises from the distribution of sodium and potassium ions. Since the electrically excitable cells of the body (nerve and muscle cells) respond to changes in these membrane potentials (see Chapter 13, pp. 468-471), it is very important to keep these electrolytes within a very narrow concentration range. When the ion count, particularly sodium ions, is too high, the body compensates by retaining water that would otherwise be excreted in the urine. Since blood pressure is related to the amount of fluid in the circulatory system, excess sodium in the body's tissues causes high blood pressure (hypertension). This is an asymptomatic condition that increases the risk of vascular (blood vessel) diseases such as stroke and coronary artery disease. Excessive use of salt (sodium chloride) worsens this condition, but is rarely the main cause. Many people in the United States are getting too much sodium and too little potassium. Potassium must be present in adequate amounts; too much or too little can lead to heart failure and death. Raisins, prunes, dates, and bananas are good sources of potassium. Other important minerals for human health are iron, calcium, fluoride and a group of trace elements. Iron. Soluble iron is necessary for the formation of blood hemoglobin and as a cofactor for many enzymes. Lack of iron in cells causes anemia, which is more common in older people with poor diets and menstruating women. In fact, iron deficiency anemia is the most common nutritional deficiency in most developed countries, including the United States. Menstruating women need almost twice as much iron as men, and pregnant women need even more for the proper synthesis of hemoglobin in the fetal blood. Vitamin C increases the cellular absorption of iron; Therefore, if the supply of vitamin C is insufficient, the cellular absorption of iron is also insufficient. Some people may be iron deficient due to low levels of proteins that carry iron in and out of cells. Calcium. Calcium (Ca2+) is required as an intracellular messenger for many processes, including muscle contraction (see Chapter 13, pp. 485-486). Furthermore, the crystalline structure of bones and teeth consists of calcium combined with phosphate and other minerals. Vitamin D promotes calcium absorption, so most people who are deficient in vitamin D also experience calcium deficiency symptoms. A high protein diet can sometimes contribute to an increase in the rate at which the kidneys excrete calcium. Many older women suffer from low bone density and brittle bones (osteoporosis). Although bones and teeth appear very immutable due to their strength, they are actually living tissues that are constantly exchanging molecules with the surrounding fluids. There is a balance between bone calcium and blood calcium; in the case of osteoporosis, the balance is disturbed and the bones release calcium. While low blood calcium levels play a role, the problem is not so simple that it can be solved by increasing dietary calcium intake later in life. Estrogenic hormones are important, as is vitamin D, which promotes calcium absorption, but the exact processes are poorly understood. Supplemental doses of calcium and vitamin D are recommended for postmenopausal women, although most bone loss in the first five years after menopause is caused by estrogen deprivation, not nutritional deficiencies. More exercise in women ages 18 to 25 can increase their bone density and prevent the development of osteoporosis later in life. Vegetarians are more likely to develop osteoporosis at a young age if they do not take care of a well-rounded diet. Fluoride. Fluoride (the F– ion) is important for the growth of strong teeth during childhood. Too little fluoride leads to a higher incidence of dental caries. Drinking water is the most important dietary source of fluoride. In some areas, natural sources of drinking water contain high levels of fluoride. The observation that people in these areas are less likely to develop cavities led to a search for possible factors. Epidemiological research showed that nearby areas had a similar diet and climate, but a higher rate of caries. Water analysis showed higher fluoride values in areas with less decay than in areas with less decay. Many municipalities now add fluoride (in carefully measured amounts) to drinking water as a preventative measure against tooth decay. Fluoride is also available in drops for infants and others without access to fluoridated water. Fluoride is toxic in very high doses. If high doses are accidentally ingested, milk can neutralize fluoride, the trace element. Most of the remaining minerals are sometimes called trace elements because they are needed by the body in very small amounts. Deficiencies in these trace elements were more common in the past when vegetables were grown locally in soils lacking in one trace element or another and when domestic animals grazing on plants grown in the same soil were the main source of pet food. . In the industrialized world, these nutrient deficiencies are much less likely because our food supply comes from multiple sources, grown in a variety of different soils and climates. In addition to the trace elements listed in Table 10.2, chromium and manganese are required for carbohydrate metabolism; Cobalt is an important component of vitamin B.12Molecule; Molybdenum and nickel are necessary in the metabolism of nucleic acids; and silicon, tin, and vanadium are needed in small amounts for proper growth, including the development of bones and connective tissues. A diet that contains enough other nutrients generally provides adequate amounts of these trace elements. Due to regional differences in the mineral content of soils, the mineral content of foods grown on these soils also varies. Therefore, mineral deficiencies often vary geographically. Zinc deficiency is common in the Middle East, for example. Iodine deficiency is more common in certain inland locations, such as the high Andes, the Himalayas, and parts of Central Africa. Newly Recognized Micronutrients In addition to the micronutrients associated with various deficiency diseases, there are other micronutrients implicated in improving human health and reducing the risk of cancer. Like vitamins, these organic micronutrients are used in very small amounts and many of them act as antioxidants. The health benefits of additional micronutrients have only been discovered in the last few decades. The name "phytochemical" is sometimes used for a diverse group of plant-derived chemicals found in foods associated with good health. Phytochemicals include lycopene in tomatoes, alkyl sulfides in onions and garlic, certain flavonoids in foods like red wine and green tea, curcumin in turmeric (a spice used in many curries), and many other compounds. . Rather than being linked to preventing a deficiency disease like scurvy or beriberi, these micronutrients are linked to lower long-term risk of heart disease and cancer. There is much more to maintaining health than simply avoiding deficiency diseases. Much of the evidence supporting the health benefits of these nutrients comes from epidemiological studies. Due to this, the mechanisms of action of these nutrients are mostly unknown. Establishing recommended dietary levels for these new micronutrients is much more difficult for several reasons. With traditional vitamins, the recommended dietary intake was generally based on the amount required by experimental animals to avoid or develop a deficiency disease, but these new micronutrients are not associated with a known deficiency disease, making it difficult to assess in a laboratory animal. has a. had a sufficient or insufficient quantity. Another problem is that these micronutrients can work in groups or in combination. For those that act as antioxidants, it is not clear whether an increase in one antioxidant can compensate for a decrease in another, which would make it nearly impossible to establish a recommended daily allowance for one in isolation from the others. Also, some of these nutrients may work better in combination, making it difficult to study any one of them in isolation. Given these uncertainties, it makes more sense to look for these nutrients in the natural combinations found in food rather than individually in pill form. Most micronutrient needs can be met economically from cereal and plant sources, even in poor countries. Cereals contain most of the B vitamins, as well as vitamin E and several important minerals, including zinc. Fresh vegetables contain additional vitamins (including A and C) and several important minerals, including calcium and iron. Fresh fruit provides additional vitamin C. In addition to protein, legumes also provide calcium and iron. Fruits, vegetables, grains, legumes, and even some spices are sources of a variety of phytochemicals. In principle, all micronutrients, with the exception of vitamin B, can be obtained from plant sources.12, the only essential vitamin that cannot be obtained solely from plant sources. Why does the intestine absorb sugar faster than starch? How do different species (like mice and humans) have different vitamin requirements? What does this mean on a biochemical level? How can some studies show that calcium supplements prevent osteoporosis while other studies do not? In Mexico, before contact with Europeans, the diet consisted mainly of corn, beans, chili peppers, and squash; The same foods remain the main components of most Mexican diets, especially in rural areas. Can you think of any biological reasons why this diet turned out to be so stable? Digestion turns food into chemicals that the body can absorb and use for energy. All organisms require energy to carry out life processes. Plants get this energy from sunlight through photosynthesis (see Chapter 11, pp. 368–72). Most other organisms, including humans, get their energy from the food they eat. However, most of the food we eat cannot be used in the form in which it is ingested. To be useful to our body, food must first be converted into substances that the body can absorb. Digestion is the process that breaks down food into absorbable products that produce energy. Digestion also serves to remove indigestible waste. Chemical and mechanical processes in digestion Digestion has two aspects: chemical digestion and mechanical digestion. In chemical digestion, food is broken down chemically using enzymes, which are substances that promote or speed up a chemical reaction without being consumed in the reaction itself (Figure 10.7). This acceleration of reactions is called catalysis in chemistry, so enzymes are biological catalysts. Almost all enzymes are proteins. Some enzymes, such as DNA polymerase (see Chapter 2, p. 59), help make molecules. Digestive enzymes, on the other hand, help break down molecules. Chemical digestion acts on the surfaces of food fragments. Mechanical digestion exposes new surface areas to chemical digestion, breaking the fragments into smaller fragments and removing partially digested surface material. The Digestive System The digestive system is one of the organ systems of the body. An organ is a group of tissues that are structurally and functionally integrated. An organ system is a group of organs that perform different parts of the same process. Therefore, the digestive system is a group of organs that work together to digest food. The layout of the human digestive system is general: from roundworms (Phylum Nematoda) to humans, most animals have digestive systems consisting of a continuous hollow tube called the intestine, with an inlet at one end and an outlet at the bottom. other. As you progress through the next few sections, locate the human digestive organs in Figure 10.8. Mouth. Food is ingested through the mouth, and mechanical digestion begins in the mouth when food is chewed. The chemical digestion of starch (carbohydrate) begins in the mouth with the enzyme called a molecule, the enzyme acts on the molecule binds to the enzyme the enzyme catalyzes a change in the molecule the altered molecule separates from the unchanged enzyme Figure 10.8 The human digestive system. salivary amylase. This enzyme present in saliva breaks down starch into smaller units (sugars). However, starch normally does not remain in the mouth long enough to be fully digested and its digestion is completed later. Another salivary enzyme called lysozyme catalyzes the breakdown of large sugar molecules (polysaccharides) into smaller units (see Figure 10.7). Stomach. After the food is swallowed, it quickly travels down the esophagus to the stomach. The stomach performs mechanical digestion through rhythmic contractions that knead food back and forth, mixing it thoroughly, rubbing food particles together, and exposing new surface areas. The main activity in the stomach is protein digestion, which is accomplished with the help of the enzyme pepsin, which breaks down large protein molecules into smaller fragments called peptides. Like many other protein-digesting enzymes, pepsin is excreted in an inactive form, which protects the glands that secrete the enzyme from digesting themselves. The inactive form becomes active absorption absorbs aquavitamin B12and other bacterial products reabsorb water and ionpepsin through digestive enzymes. Pepsin works best in an acidic solution, which the stomach supplies through the secretion of hydrochloric acid (HCl). Acidity is measured on a scale called the pH scale; The lower the pH, the more acidic the solution (Figure 10.9). The fluids in the stomach are some of the most acidic in biological systems, with a typical pH of 2. The stomach also secretes mucus that protects the stomach lining (which is made up in part of protein) from pepsin and acid. The small intestine: fat processing. The lower end of the stomach empties into the small intestine, where the pH is no longer acidic. The term "small" refers to the diameter, which is about 3 cm; The small intestine is actually quite long (20 feet or 6 m). Here the food receives the secretion of the liver called bile. In the watery environment of the intestine, fats tend to come out of solution and form large globules that fuse into larger globules with each collision. The bile breaks down the fat globules into smaller droplets and keeps them separate. Fats are insoluble in water because their chemical bonds are nonpolar, whereas those of water are polar (see Figure 10.2). Bile prevents the formation of blood cells. A portion of each bile molecule is polar and therefore stable in water; another part is nonpolar and therefore unstable in water but stable in fat. The nonpolar parts of the bile molecules dissolve in the fat droplets, leaving behind the polar parts of Figure 10.9 The pH scale. The pH of a solution tells us the concentration of hydrogen ions (H+) in the solution. The H+ concentration can be expressed in moles of H+ per liter of solution, as shown to the left of the bar. However, it is more common to express the concentration as a pH value, which is displayed to the right of the bar. The pH scale is a reciprocal scale: the lower the pH, the higher the H+ concentration (and the more acidic the solution), and the higher the pH, the lower the H+ concentration (and the more basic the solution). The pH scale is also a logarithmic scale; that is, each number differs by a factor of 10 from those surface-exposed molecules in contact with aqueous intestinal fluids. The polar coating helps the fat droplets mix with the water and also prevents small droplets formed by mechanical action from recombining into large globules (Figure 10.10). This preserves the greater surface area of many small fat droplets and increases the efficiency of digestion, as a much greater surface area is available for digestion and absorption. Bile is excreted by the liver in a constant trickle, but10010-110-210-310-410-510-610-710-810-90 hydrochloric acid (HCl) car battery acid 1 stomach acid (1.0-3.0) lemon juice (2.3) vinegar , wine, soft drinks, orange juice, strong acid rain tomatoes, grapes, bananas (4.6) black coffee normal rainwater urine (5-7) milk (6.6) saliva (6.2-7.4) pure human blood water (7.3-7.5) protein (8.0) seawater (7.8-8.3) ) antacid tablets the next number. Therefore, a pH 2 solution has 10 times more H+ ions than a pH 3 solution. It is used in large quantities when there are fats or oils in the intestine. Bile from the liver accumulates in the gallbladder until it is needed and is then released all at once under the stimulation of a digestive hormone. A hormone is a chemical messenger that carries a specific phosphate 10–1010–1110–1210–1310–14 detergents bleach soap solutions milk of magnesia household ammonia (10.5–11.9) phosphate-free detergents12 epilators 13 oven cleaners 14 sodium hydroxide (NaOH) Figure 10.10 The effect of bile salts on the breakdown of fats. Physiological change in one or more target organs. There are many types of hormones with very different functions; In Chapter 9, we discuss the functions of some reproductive hormones. The intestinal mucosa secretes a digestive hormone whenever there are fats in the intestine; it acts on the gallbladder, its target organ, and stimulates the release of bile in the intestine. The small intestine: digestive enzymes. Further down the small intestine, chemical digestion is completed by enzymes secreted by the pancreas and intestinal lining. Enzymes are often named by combining the suffix "-ase" with the name of the molecule the enzyme is working on: proteases break down proteins, lipases break down lipids, etc. Intestinal enzymes include the following: Proteases, protein-digesting enzymes such as trypsin and chymotrypsin secreted by the pancreas. Other proteases are secreted by the small intestine. Like pepsin in the stomach, these enzymes break chemical bonds between certain amino acids, breaking down proteins into smaller chains of amino acids called peptides. Each protease is specific and only breaks the bonds between certain specific amino acids. Peptidases, enzymes that complete the final stages of protein digestion by breaking down peptides into individual amino acids. Both the pancreas and the intestinal mucosa secrete peptidases. Pancreatic amylase, an enzyme secreted by the pancreas. This enzyme continues the job started in the mouth of breaking down starch into sugar. Lipases, fat-digesting enzymes secreted by the pancreas and intestinal lining. These enzymes break down fats and oils into glycerol and fatty acids, molecules small enough to be absorbed, such as glucose and fructose. The presence of digestive enzymes can vary in human populations. We saw in Chapter 7 that northern Europe has less exposure to ultraviolet radiation than other regions of the world, and therefore populations living in northern Europe have less sunlight to help them synthesize vitamin D. vitamin D , most Europeans consume dairy products rich in vitamin D , and these dairy products also contain significant amounts of lactose, the sugar in milk. Thus, natural selection acted in European populations to favor those individuals that possessed the enzyme lactase, necessary to digest lactose. Outside of Europe, ultraviolet radiation is generally sufficient for the synthesis of large amounts of vitamin D, so dairy products are not necessary in the adult diet. Because they don't need to digest lactose, people in this demographic often lack the lactase enzyme. When a lactase-free person consumes most dairy products, unused lactose is fermented by intestinal bacteria, producing large amounts of carbon dioxide gas that causes painful cramps, diarrhea, and sometimes vomiting. This condition is known as lactose intolerance. The small intestine: nutrient absorption. The resorbable part of the intestine (ileum) is lined internally with thousands of tiny finger-like tufts (villi) that greatly increase the surface area through which the products of digestion are absorbed. Absorbable products include simple sugars, glycerol, fatty acids, and amino acids. Water and mineral salts are also absorbed, including dissolved ions (charged atomic particles) of sodium, calcium, and chloride, which do not need to be digested to be absorbable. The absorption process will be described later. The colon: our mutual relationship with intestinal bacteria. The material that is not absorbed by the ileum ends up in the large intestine, which is also called the large intestine for the most part. Compared to the small intestine, the large intestine is larger in diameter (6 to 7 cm or 2.5 inches) but much shorter (1.2 m or 4 feet). This part of the intestine is inhabited by many bacteria and certain nutrients produced by the bacteria are absorbed here. Mammals cannot produce the enzymes that digest cellulose, the main component of plant cell walls. The bacteria that live in the intestine, and especially in a small cul-de-sac (called the cecum or cecum), have to do this for them. The cecum is particularly important (and much larger as well) in herbivorous mammals such as horses and rabbits, which consume large amounts of cellulose. Since we are mammals, we humans cannot produce enzymes that break down cellulose, nor do we have the right kind of gut bacteria to digest cellulose for us, so we cannot digest cellulose. However, we do get some necessary nutrients from our gut bacteria. Humans cannot produce vitamin K and biotin, which are necessary for the synthesis of blood clotting factors and for the synthesis of fatty acids, but our gut bacteria can synthesize them and we can absorb these micronutrients. Intestinal bacteria live in a kind of symbiosis with vertebrate organisms. Symbiosis simply means that two organisms live together; Mutualism is the form of symbiosis in which the two species benefit from each other. Mutualistic gut bacteria obtain nutrients from the food their human host eats. In turn, they synthesize the vitamins humans need and break down many complex molecules into simpler components that are easier for the intestine to absorb. The symbiosis can be disrupted by factors such as antibiotics, which kill the bacteria. The large intestine: water absorption. The rest of the large intestine consists of a straight part, the rectum, which leads to a final opening called the anus. In the colon and rectum, water is absorbed primarily by diffusion from material flowing through the intestine, giving that material a firmer consistency. Much of this material, known as feces, is undigested food, but more than half is intestinal bacteria, which are rapidly replaced by bacterial cell division in the intestine. It is partly these bacteria and partly the bile pigments that give stool its characteristic brown color. Conversion of macronutrients into cellular energy Carbohydrates, fats and proteins are all macronutrients, the main sources of calories in the body. After the large macromolecules are broken down into single subunits in the digestive system, the cells take up the subunits. They are first absorbed by the cells lining the digestive tract and then carried through the blood to all other cells in the body. Once inside a cell, these simple subunits can trigger a series of reactions that result in energy being stored in the form of a molecule called ATP (adenosine triphosphate). ATP is one of the main molecules in which chemical energy is stored for later use by the cell. Therefore, food provides the opportunity to produce the ATP that our cells use ATPP.UEAdenosine triphosphateAdenosine diphosphateInorganic phosphateFor all your jobs.Absorption. Food cannot be converted to LDL energy-low-density lipoproteins until they have been absorbed. Absorption takes place across the cell membrane of cells lining the plasma membrane for passive diffusion into the intestine. The polar chemical structure of most digestive products means that they cannot enter the cell directly because the interior of the cell membrane is nonpolar. Therefore, the membrane acts as a controller of what enters (or leaves) the cell. Chemicals are absorbed by one of four mechanisms (Figure 10.11); these mechanisms also carry chemicals to other cells in the body. concentration gradient (D) two forms of endocytosis facilitated diffusion plasma membrane © active transport concentration gradient plasma membrane concentration gradient receptor-free uptake receptor-mediated endocytosis Some small molecules enter cells by diffusion, a process that requires no additional energy and therefore, it is sometimes called "passive diffusion" (see Figure 10.11A). Diffusion only works when there is a concentration gradient; Any substance diffuses from a place where it is more concentrated to a place where it is less concentrated. Small uncharged molecules, such as water (H2O) u oxygen (O2) diffuse directly across the cell membrane. Charged molecules cannot cross the membrane, but can diffuse through channels, protein-filled "holes" in the membrane. Small polar molecules often move into cells with the help of protein molecules (called transport proteins) that span the cell membrane. When this transport occurs along a concentration gradient, it is called facilitated diffusion (see Figure 10.11B). Other molecules are absorbed against the concentration gradient, i. H. from an area of lower concentration to an area of higher concentration of this type of molecules. This process requires an input of energy (usually from the breakdown of ATP) and is called active transport (see Figure 10.11C). Membrane proteins bind to the molecule to be transported and expend energy to transport it across the membrane. Large particles can enter the cell through a process called endocytosis (see Figure 10.11D), which pushes the plasma membrane into the cell. The plasma membrane forms a pit that can contain large particles; then the edges of the pit are closed and the pit is compressed to form a vesicle within the cell. This bulk process transports many molecules at once, either suspended in liquid or attached to membrane proteins called receptors. Forms of energy release. The ingested small molecules are then broken down into even smaller molecules, as can be seen in Figure 10.12. The long carbon chains of fatty acids break down gradually. At each stage, two carbons from the long carbon chains are broken to form an acetyl group. Each of these acetyl groups is attached to a carrier molecule called coenzyme A, so the complex is called acetyl-coenzyme A (acetyl-CoA). The various amino acids break down into pyruvate or acetyl-CoA or one of the Krebs cycle molecules (see below). Sugars like glucose are converted to a three-carbon molecule called pyruvate through a process called glycolysis. The pyruvate is then converted to acetyl-CoA. During glycolysis, limited amounts of ATP, a high-energy molecule, are synthesized. Glycolysis is one of the oldest known metabolic pathways and is found in most living organisms. Pyruvate and acetyl-CoA, which are formed when proteins, carbohydrates, or fats are broken down, are then transported from the cytoplasm to organelles called mitochondria (see Chapter 6, pp. 169-170), where they are used in a reaction cycle. Krebs cycle, more energy is removed. Two ATP molecules are synthesized in each cycle. Figure 10.12 How the major products of digestion are broken down in a series of energy-producing reactions. The enzymes for this process are proteins within the mitochondria, including some attached to the inner mitochondrial membrane. A molecule of a compound called oxaloacetate combines with the two carbons carried by acetyl-CoA, and a series of oxidation reactions remove electrons from hydrogen atoms, removing energy at each of several biochemical steps (see Figure 10.12). The hydrogens from these oxidation reactions are taken up by a molecule called NAD+ (which forms NADH) and then delivered to a series of mitochondrial membrane protein complexes called the electron transport chain, which pass electrons from one protein to the next. These protein complexes are aligned in the membrane so that each time an electron passes from one electron carrier to the next electron carrier in the chain, a proton (H+) is pumped from one side of the mitochondrial membrane to the other. This creates an uneven distribution of protons on opposite sides of the membrane (called a proton gradient). This protonproteincarbohydratesfatsindividual amino acidssimple sugars (eg, glucose)glycerol fatty acidsindividual sugarsglucose-6-phosphateglycerolindividual amino acids of the plasma membrane NADHacetylchoamitochondrialmembraneCODH2ATPoxalo2-cetoglutarato NADH
CO2
The gradient is a gradient of chemical and electrical charge, two important ways in which energy can be stored for later use by the cell. Some of this stored energy is used by an enzyme called ATP synthase, which produces additional ATP. Eventually, after gradually losing energy, the electrons combine with oxygen, which is why we have to breathe oxygen from the atmosphere. The energy drain processes in mitochondria are shown in Figure 10.13. Several steps in the Krebs cycle and electron transport require vitamins as coenzymes. As an example of a vitamin's function as a coenzyme, consider the role of the vitamin thiamine in breaking down the pyruvate molecule. An enzyme containing thiamine as one of its constituents combines with the pyruvate molecule and releases CO2, then emerges in its original form from a later reaction. Since thiamine is not consumed, it can always participate in the reaction. Because of this, only small amounts of thiamine are needed to facilitate the breakdown of large amounts of pyruvate formed in carbohydrate metabolism. B vitamins2mi B3they are part of the larger molecules that transport electrons from the Krebs cycle to the electron transport chain (see Figure 10.13). Digestion thus culminates in chemical changes at the cellular level. The process of converting food to ATP begins with the food and ends when the electrons accept oxygen. Each cell breaks down sugars and other organic molecules and converts their chemical binding energy into ATP. This process is called a cell. Figure 10.13 Energy-producing processes that occur in mitochondria. Electrons are shown as e- and protons (hydrogen ions) as H+. Long breath. Eventually, many of the carbon atoms in food molecules mix with oxygen as carbon dioxide (CO2) exuded by the body. Hydrogen atoms in food split: their protons form gradients and their electrons are transported to finally recombine with oxygen to form water (H2EITHER). At each intermediate step,1 the Krebs cycle converts the chemical binding energy of food into energy stored by electrons in NADH molecules. Pyruvate and Acetyl-CoAKrebs Cycle2 Electrons transfer energy from NADH to a series of ATP electron transport proteins. Other types of organisms obtain energy by transporting carbon and hydrogen to molecules other than oxygen, which allows them to live in the absence of oxygen, NAD+Proteins of the electron transport chainNADH2e–
H+
O + 2e–
2 hours+H2O
H+H H+ H+ATP ADP + PUEaber viel mehr Energie kann der Nahrung entzogen werden, wenn Sauerstoff als Endakzeptor verwendet wird. Essen bewirkt, dass der zelluläre ATP-Produktionsprozess auf Hochtouren schwingt und ATP für den sofortigen Gebrauch und zur Speicherung für zukünftigen Bedarf produziert ?Was würde passieren, wenn die Nahrung den Magen zu früh verlässt?Der Inhalt des Verdauungstraktes wird durch rhythmische Muskelarbeit (Peristaltik) eher langsam vorangetrieben. Wie hängt dies mit dem Bedarf des Körpers an einem langen Darmtrakt zusammen? Was wären die Folgen einer Mutation, die verhindert, dass der Körper eines Menschen ein Membranprotein herstellt, das für den aktiven Transport von Zucker aus dem Darm erforderlich ist? in kleinere Moleküle verdaut, bevor sie vom Darm absorbiert werden können? Absorbierte Nährstoffe zirkulieren im ganzen Körper Nachdem Nährstoffmoleküle im Dünndarm absorbiert wurden, zirkulieren sie im ganzen Körper. Andere Materialien, einschließlich gelöster Ionen, Sauerstoff und Zellen des Immunsystems, zirkulieren ebenfalls durch den Körper.KreislaufsystemDer Kreislauf von Materialien wird durch das Kreislaufsystem durchgeführt. Bei allen Wirbeltieren besteht dieses System aus Blut, das in einer Reihe von Blutgefäßen enthalten ist, und dem Herzen, einer Muskelpumpe, die das Blut zirkulieren lässt. Das Blut besteht aus einem flüssigen Material (dem Plasma), das eine Reihe von Zellen und Blutplättchen enthält . Zu den Zellen gehören die roten Blutkörperchen (Erythrozyten), die das sauerstofftragende Molekül Hämoglobin enthalten (siehe Kapitel 7, S. 229–231), und verschiedene Arten von weißen Blutkörperchen, die das Immunsystem bilden (siehe Kapitel 15, S 542–543). Die Blutplättchen sind Zellfragmente, die für die Blutgerinnung wichtige Stoffe freisetzen. Ebenfalls wichtig bei der Gerinnung ist ein lösliches Protein, Fibrinogen, eines von mehreren löslichen Proteinen, die im Plasma zirkulieren. Wenn eine Wunde Fibrinogen mit der Luft in Kontakt bringt, kann es zu einem unlöslichen Knäuel werden, in dem Zellen eingeschlossen werden. Dieses Gewirr und seine eingeschlossenen Zellen bilden das Blutgerinnsel, das den weiteren Blutverlust blockiert und den Prozess der Wundheilung einleitet. Das Blut zirkuliert durch eine Reihe größerer und kleinerer Blutgefäße. Die vom Herzen wegführenden Gefäße nennt man Arterien. Die zum Herzen zurückführenden Gefäße werden Venen genannt. Die Arterien verzweigen sich in immer feinere Gefäße. Die Venen sind als eine Reihe von Nebenflüssen angeordnet, die in größere Gefäße und schließlich zurück zum Herzen fließen. Die dünnsten Gefäße, Kapillaren genannt, transportieren Blut von den kleinsten Arterien zu den kleinsten Venen (Abb. 10.14). Die Kapillarwände sind eine einzelne Zellschicht. Materialien diffundieren von Kapillaren in Gewebe und von Geweben in Kapillaren über die Zellen der Kapillarwände. Die sehr große Kapillaroberfläche ermöglicht eine großflächige Diffusion. Im ganzen Körper ist keine Zelle oder Gewebe sehr weit von einer Kapillare entfernt. Im Darm aufgenommene Nährstoffe gelangen in die Kapillaren der Darmschleimhaut und fließen über die Pfortader der Leber zur Leber. Enthält das Blut mehr Glukose, als der Körper sofort benötigt, wird der Überschuss in das Speichermolekül Glykogen umgewandelt. Die Glykogenspeicherung findet in den meisten Körperzellen statt, aber die größte Menge wird in der Leber gespeichert. Wenn der Körper Blutzucker verbraucht, wandeln die Leberzellen Glykogen wieder in Glukose um und geben sie nach Bedarf in den Blutkreislauf ab, ein Mechanismus, der eine zuverlässige, aber moderat niedrige Glukosekonzentration im Blut gewährleistet. Die Speicherung von Glykogen und die effiziente Nutzung von Glukose erfordern beide das Hormon Insulin, das von speziellen Zellklumpen in der Bauchspeicheldrüse ausgeschüttet wird. Personen, bei denen diese Zellen entartet sind, können nicht genug Insulin produzieren; ihr Zustand ist als insulinabhängiger Diabetes mellitus (IDDM oder Typ-I-Diabetes) bekannt. Die Symptome von Diabetes können durch die Zufuhr von Insulin oder durch die Kontrolle von Gewicht und Ernährung kontrolliert werden, aber es gibt kein bekanntes Heilmittel für die Krankheit selbst. Blut aus der Leber und anderen Organen des Körpers fließt durch die Venen zum Herzen. Die meisten Venen haben dünne, flexible Wände und das Blut in ihnen fließt mit einem relativ niedrigen Flüssigkeitsdruck. (Im Gegensatz dazu haben Arterien dicke Wände, die dem hohen, pulsierenden Flüssigkeitsdruck des Blutes in ihnen standhalten können.) Das Blut in den Venen wird durch die Massagewirkung der nahe gelegenen Muskeln und anderer Organe angetrieben. Klappen in den Venen sorgen dafür, dass das Blut in eine Richtung fließt und verhindern, dass es zurückfließt. Neben der Verteilung von Nährstoffen verteilt das Kreislaufsystem auch Sauerstoff im Körper und transportiert Kohlendioxid (ein Abfallprodukt der Zellatmung) von den Körperzellen zur Lunge (die es dann ausatmet). Abbildung 10.14 Das menschliche Kreislaufsystem. Das Blut zirkuliert durch das Herz und verhindert, dass sich Sauerstoff und Kohlendioxid vermischen. Das Herz Das Herz ist ein Muskelorgan, dessen rhythmische Kontraktionen dafür sorgen, dass das Blut durch den Körper zirkuliert. Bei allen Säugetieren enthält das Herz vier Kammern (Abb. 10.15). Sauerstoffarmes Blut aus den verschiedenen Organen des Körpers gelangt in den rechten Vorhof und wird in die rechte Herzkammer gepumpt. Die Kontraktion des rechten Ventrikels treibt das Blut durch die Pulmonalarterien und in die Vene, obere Hohlvene, Kapillaren, rechte Lunge, Kopf und Arme, Kapillaren, Aorta, Herzarterie, Lungenarterie, linke Lunge, Kapillaren, Lungenvene, Lunge. Hier diffundiert der Sauerstoff in den winzigen Lungenbläschen oder Alveolen (siehe Kapitel 14, S. 503–504) ins Blut, während Kohlendioxid ausdiffundiert und ausgeatmet wird. Sauerstoffreiches Blut aus der Lunge kehrt zur linken Seite des Herzens zurück, wo es in den linken Vorhof eintritt. Kontraktion der unteren HohlveneVenenKapillareninnere OrganeKapillarenBeineabsteigende Aorta Arteriensauerstoffreiches Blut sauerstoffarmes Blut Die Kontraktion des linken Ventrikels treibt das Blut durch die Arterien und in die verschiedenen Organe des Körpers; Aus diesem Grund hat es die dicksten Wände. Sauerstoff diffundiert aus dem Blut in die vielen Körperzellen über die dünnen Kapillarwände, und Zellabfälle, einschließlich Kohlendioxid, diffundieren aus den Zellen in das Blut. Die Venen sammeln dieses sauerstoffarme Blut aus den verschiedenen Organen des Körpers und transportieren es zurück zum Herzen, wo sich das Kreislaufmuster wiederholt (siehe Abbildung 10.14). Das Herz behält sein eigenes rhythmisches Kontraktionsmuster bei. Ein Herz, das einem lebenden Tier entnommen und in eine Salzlösung gelegt wird, schlägt noch viele Stunden weiter. Der Rhythmus wird auch ohne Nerveneingabe aufrechterhalten, was zeigt, dass der Herzrhythmus im Herzen selbst entsteht. In den Vereinigten Staaten sterben jedes Jahr 500.000 Menschen an Herzkrankheiten, was sie zur Todesursache Nummer eins macht. Weitere 1,5 Millionen haben nicht tödliche Herzinfarkte. Jedes Jahr sterben fast 500.000 Menschen an Schlaganfällen, einer Blutgefäßkrankheit. Männer haben früher mehr Herz-Kreislauf-Erkrankungen als Frauen (Verhältnis Männer: Frauen insgesamt 2:1), aber Herz-Kreislauf-Erkrankungen sind dennoch die Haupttodesursache sowohl bei Männern als auch bei Frauen. Risikofaktoren für Herz-Kreislauf-Erkrankungen sind Rauchen, Übergewicht, fettreiche Ernährung, Bewegungsmangel, Bluthochdruck, Atherosklerose, hohe Cholesterinwerte, Stress und genetische Veranlagung. Richtige Ernährung, Bewegung, Gewichtsverlust und Stressabbau sind die wichtigsten Möglichkeiten, um die Risiken zu verringern. Zu viel Nahrungsfett. Die Untersuchung von Krankheitsfaktoren in großen Populationen wird als Epidemiologie bezeichnet. Epidemiologische Studien deuten auf eine Verbindung von oberer Hohlvene (von Kopf und Armen) rechter Pulmonalarterie (zur Lunge) rechtem Vorhof rechter Ventrikel unterer Hohlvene (vom Körper) zu Kopf und Armen linke Pulmonalarterie (zur Lunge) Lungenvenen (von der Lunge) Lungenstamm linker Vorhoflinker Ventrikelzwischen bestimmten Arten von Nahrungsfetten und Herz-Kreislauf-Erkrankungen (Herzerkrankungen und Schlaganfälle). Die Vereinigten Staaten, Australien und Neuseeland – allesamt fleischproduzierende Länder – haben eine hohe Konsumrate von Fleischprodukten pro Person und auch eine hohe Inzidenz von Herz-Kreislauf-Erkrankungen. Die meisten Fleischsorten sind reich an gesättigten Fetten. Die Menschen in den Mittelmeerländern konsumieren einen Großteil ihrer Lipide in Form von Olivenöl, einem ungesättigten Fett, und ihre Raten für Herz-Kreislauf-Erkrankungen sind geringer. Herzinfarkte sind bei den Inuit (Eskimos) sehr selten, deren Ernährung große Mengen an Kaltwasserfischen enthält, eine gute Quelle für eine Art von Fettsäure namens Omega-3-Fettsäure sauerstoffreiches Blut sauerstoffarmes Blut absteigende Aorta (zu senken Hälfte des Körpers), die nachweislich die Produktion von Chemikalien verhindert, die Zellmembranen schädigen. Die Japaner neigen auch dazu, niedrige Konsumraten von gesättigten Fetten und niedrige Raten von Herz-Kreislauf-Erkrankungen zu haben. Die Epidemiologie gibt auch Hinweise darauf, ob der Zusammenhang zwischen Nahrungsfetten und Herz-Kreislauf-Erkrankungen enger mit der Ernährung oder mit genetisch vererbten Merkmalen zusammenhängt: Japaner in Japan haben viel niedrigere Raten von Herzkrankheiten oder Schlaganfällen als Japaner, die auf Hawaii oder Kalifornien leben, deren Raten denen ihrer nichtjapanischen Nachbarn ähnlich sind. Diese Ergebnisse (und ähnliche zu anderen Einwanderergruppen) weisen alle auf die Ernährung und nicht auf die Vererbung als den Hauptunterschied hin, der für die unterschiedlichen Krankheitsraten zwischen den Bevölkerungsgruppen verantwortlich ist. Da gesättigte Fette mit einem höheren Risiko für Herz-Kreislauf-Erkrankungen in Verbindung gebracht werden, empfehlen viele Experten dies Gesättigte Fette werden in den meisten Diäten durch ungesättigte Fette ersetzt. Die Werbung hat viele Menschen davon überzeugt, dass ungesättigte Fette – insbesondere die mehrfach ungesättigten – wünschenswert sind, aber das gilt nur, wenn diese Fette gesättigte Fette ersetzen. Die meisten Experten empfehlen, die Mengen aller Nahrungsfette zu reduzieren, um das Risiko von Herz-Kreislauf-Erkrankungen zu senken. Arteriosklerose. Nahrungsfett kann das Risiko für Herz-Kreislauf-Erkrankungen auf verschiedene Weise erhöhen. Eine Möglichkeit besteht darin, dass überschüssiges Nahrungsfett zu Fettablagerungen führen kann, die sich in den Arterien ansammeln und Arteriosklerose verursachen (Abbildung 10.16), eine Art von Herz-Kreislauf-Erkrankung, die zu Herzinfarkten führen kann. Die Fettablagerungen verstopfen die Blutgefäße und verengen die Durchgänge; schließlich können diese Ablagerungen verkalken und die Gefäße steifer machen. Atherosklerose trägt zu Bluthochdruck (Bluthochdruck) bei, obwohl eine Person Bluthochdruck haben kann, ohne Atherosklerose zu haben.LDLs und HDLs: Lipidtransportpartikel. Im Gegensatz zu Kohlenhydratmolekülen enthalten Lipidmoleküle wenige Sauerstoff- und Stickstoffatome und haben meist unpolare Bindungen, in denen Elektronen gleichmäßig um Kohlenstoff- und Wasserstoffatome verteilt sind (siehe Abbildung 10.2). Da die Bindungen in Lipiden unpolar sind, sind Lipide nicht wasserlöslich. Blutplasma besteht hauptsächlich aus Wasser, daher müssen Lipide durch Transportpartikel wie LDLs (Low Density Lipoproteins) und HDLs (High Density Lipoproteins) durch das Blut von einem Teil des Körpers zum anderen transportiert werden. Diese Transportpartikel sind Proteine, die Lipide so binden, dass sie sich durch Körperflüssigkeiten bewegen können. Menschen, die sich identisch ernähren, haben möglicherweise nicht denselben Serumcholesterinspiegel. Dieser Unterschied scheint eine genetische Komponente zu haben und hängt zum Teil mit der Fähigkeit jeder Person zusammen, den effektiven Durchmesser einer Arterie zu reduzieren. Obwohl sich der Außendurchmesser des Gefäßes nicht verändert hat, ist der Innendurchmesser (Lumen), durch den das Blut fließt, durch die Bildung von Lipidablagerungen an der Gefäßinnenseite kleiner geworden, wodurch der Blutdruck steigt. Diese Ablagerungen können auch verkalken, was den Blutdruck weiter erhöht. machen LDLs und HDLs. Niemand hat sehr viel freies (ungebundenes) Cholesterin, weil Cholesterin sehr unpolar ist. Was als Serumcholesterin bezeichnet wird, ist also eigentlich die Gesamtheit des gesamten Cholesterins, das an HDLs und LDLs gebunden ist. HDLs transportieren Cholesterin, Phospholipide und Triglyceride aus Geweben zur Leber, wo sie bei der Synthese von Gallensäuren verwendet werden, während LDLs Cholesterin und Lipide in Gewebe und Zellen transportieren. Das HDL:LDLNORMAL ARTERY ATHEROSCLEROTIC ARTERYArterienwand-Außenschicht-Mittelschicht-Innenschicht-Lumen-Plaque-Verhältnis ist das Verhältnis von ausgehenden zu eingehenden Lipiden. Ein hohes HDL:LDL-Verhältnis zeigt also an, dass der Anteil des „guten Cholesterins“ (Lipide auf dem Weg nach draußen) höher ist als der Anteil des „schlechten Cholesterins“ (Lipide auf dem Weg in die Zellen). Ein sehr niedriges Verhältnis, d. h. ein Übergewicht an eingelagerten Lipiden, korreliert stark mit einem erhöhten Risiko für Atherosklerose in den Arterien des Herzens (Koronararterien), einem Zustand, der einen Herzinfarkt auslösen kann. Manche Menschen sind genetisch anfällig für hohe Cholesterinwerte ihren Zellen fehlen LDL-Rezeptoren auf ihren Oberflächen. Wenn Zellen Cholesterin benötigen, erhalten sie das Cholesterin aus den LDLs im Blutkreislauf, indem sie diese Partikel an LDL-Rezeptoren binden und die Rezeptoren und LDLs durch Endozytose internalisieren (siehe Abbildung 10.11D). Fehlen oder funktionieren die LDL-Rezeptoren nicht, produzieren die Zellen auch bei bereits hohen LDL-Werten ihr eigenes Cholesterin, weil sie LDL nicht aus dem Blut aufnehmen können. Somit ist die Ernährung nicht der einzige Faktor, der zu Arteriosklerose führt; Probleme mit dem Lipidtransport und der Lipidaufnahme sind ebenfalls Faktoren. GEDANKENFRAGEN1 Krebs ist keine so häufige Todesursache wie Herzerkrankungen, dennoch scheint die Krebsforschung mehr Publicity zu erhalten als die Forschung zu Herzerkrankungen. Untersuchen Sie einige Zeitungen und Zeitschriften, um zu sehen, ob dies ein richtiger Eindruck ist. Wenn ja, welche Faktoren könnten zu diesem Unterschied beitragen?2 Das menschliche Kreislaufsystem ist ein kontinuierliches, geschlossenes System; Mit anderen Worten, keines der Blutgefäße ist offen. Warum muss das so sein?Mangelernährung trägt zu schlechter Gesundheit beiDer Begriff Mangelernährung bedeutet wörtlich „schlechte Ernährung.“ Mangelernährung kann durch zu wenig oder falsche Ernährung entstehen und ist eines der größten Gesundheitsprobleme der Welt, insbesondere unter den Armen und in Krisengebieten. Mangelernährung existiert auch bei Menschen mit Zugang zu ausreichender Nahrung, teilweise als Folge von Essstörungen. In den Industrienationen überwiegen Essstörungen. Fettleibigkeit. In den Vereinigten Staaten schätzt das Center for Disease Control and Prevention (CDC), dass 40 % der Erwachsenen fettleibig sind. Adipositas ist definiert als ein Körpergewicht, das 20 % oder mehr über dem Idealwert für das Geschlecht und die Körpergröße des jeweiligen Probanden liegt, oder ein Body-Mass-Index (BMI) von 30 oder mehr (Kasten 10.2). Fettleibigkeit erhöht das Risiko für Bluthochdruck, Herzkrankheiten, Schlaganfall, Diabetes und verschiedene Krebsarten (einschließlich Dickdarm-, Brust- und Prostatakrebs). Die CDC hat erklärt, dass Fettleibigkeit eine der größten Bedrohungen für die öffentliche Gesundheit in den Vereinigten Staaten ist. Zahlreiche Faktoren tragen zur Fettleibigkeit bei. Es gibt einige genetische Beiträge zum relativen Anteil an Körperfett oder Kohlenhydraten, der für KASTEN 10.2 Fettleibigkeit und der Body-Mass-Index (BMI) verwendet wird. Die neuen Definitionen von Übergewicht und Fettleibigkeit basieren auf dem Body-Mass-Index (BMI), der wie unten beschrieben berechnet wird. Eine Person mit einem BMI von 25 oder mehr gilt als übergewichtig, und eine Person mit einem BMI von 30 oder mehr als fettleibig. Auf der Grundlage dieser Kriterien schätzt die CDC, dass über 60 % der Erwachsenen in den Vereinigten Staaten übergewichtig oder fettleibig sind, und sie haben Fettleibigkeit zu einer „Epidemie der öffentlichen Gesundheit“ erklärt. Die CDC (atwww.cdc.gov/nccdphp/dnpa/obesity) lists a total of 20 disease conditions to which overweight or obesity contributes.TO CALCULATE YOUR BODY MASS INDEX:Divide your weight by your height, then divide by your height again. (The formula is BMI = w/h2.)If you measured your weight in kilograms and your height in meters, the result is your BMI.If you used kilograms and centimeters, multiply the result by 10,000 to get your BMI.If you used pounds and inches, multiply the result by 703.7 to get your BMI.According to the CDC, the incidence of overweight and obesity has been increasing in the United States.Percent of U.S. Overweight but not Obese (BMI Total overweight adults obese (BMI 25–29.9) 30 or above) (BMI 25 or above)1980 33% 15% 48%1999–2000 34% 30% 64%energy production and to the likelihood of energy surplus being stored as fat versus lean tissue. However, environmental factors are much stronger for most people than are genetic ones. Factors that encourage obesity include decreased exercise, increased calorie intake, and increased consumption of fatty foods. In many cases the amount of excess weight is proportional to the number of meals eaten away from home, where portions are large and fat content is high.The marketing of food (including its advertising and packaging) encourages unhealthy behavior and overeating. High-calorie or high-fat foods are advertised heavily. Many foods, especially snack foods, are packaged in individual serving units that are convenient for a person on the go (often in containers that fit into the cup holders of automobiles), and these individual serving units can be much larger than any serving recommended by nutritionists, sometimes as much as two or three times as large. Fast food is often marketed in “super size” portions, and customers are encouraged to have side orders of fried foods and beverages consisting of calorie-rich and vitamin-poor sodas and shakes. Eating in the car or while working or watching TV are forms of ‘unconscious ’ eating that can prevent a person from being aware of how much they have eaten.Many people attempt to reduce their weight by dieting. Some major facts about dieting are widely agreed upon by nutritionists. For example, many different diets can be effective in helping to reduce weight. The diets that work do so by reducing caloric intake. Some diets that are nutritionally very unbalanced can be harmful. Of course, no person can achieve results on a diet that they cannot stay on, and different peopleFigure 10.17One of the earliest signs of anorexia is misperception of one’s own body.find different diets easier or harder to stick to. Unfortunately, most people who lose weight by dieting gain back what they lost (often more than what they lost) within a few months or so after stopping their diet.Anorexia and bulimia. In the middle and upper classes of the industrialized nations, some people suffer from a condition called anorexia nervosa. The ratio of anorexic women to anorexic men is about 9:1. Anorexic individuals suffer from a mistaken perception of their body size. They imagine themselves to be heavier than they really are, and desire to be thinner as a result, a feature that clearly distinguishes anorexia from all other forms of undernourishment (Figure 10.17). Anorexics also respond poorly to body cues of hunger and satiety. The misperception of hunger, satiety, and body size are early symptoms that precede the most noticeable feature of the disease, what American (German-born) physician Dr. Hilde Bruch has called a “relentless pursuit of thinness,” a self-imposed undernourishment that borders on starvation. At the same time, there is usually an absorbing or obsessive interest in food, which may include talking or reading about food, preparing food, collecting recipes, or serving food to others, while all the time avoiding eating.One of the surest signs of the disease in anorexic women is that they usually stop menstruating because of a lack of the cholesterol needed for synthesis of the hormones that regulate the menstrual cycle (see Chapter 9, pp. 299–300). Other symptoms include changes in brain activity. The brain must be constantly supplied with glucose to provide cellular energy for nerve cell function; when it is not, many mental functions may be impaired. These impairments may manifest themselves in anorexic persons as deception (hiding things, keeping secrets) and a distrust of others, but only late in the process, after starvation has already set in. Untreated anorexia is usually fatal.Anorexia is most common among Caucasian women between the ages of 15 and 30 years with an average or above-average level of educa-tion. The disease also occurs in Japan and in parts of Southeast Asia, but only in the uppermost social strata. Anorexia is virtually unknown among people living in poverty or in undernourished populations anywhere. It never seems to occur where food is scarce, or in times of famine. Even in countries where it occurs, it seems to vanish during economic hard times, such as the Depression of the 1930s.Anorexia was once extremely rare. Its marked increase in the United States since World War II has been attributed by several experts to a general standard of beauty that has increasingly glorified thinness, as measured by such criteria as waist and hip measurements of Miss America contestants, Playboy centerfolds, and models and ballet dancers more generally. In fact, women in professions such as modeling and ballet dancing are particularly likely to develop anorexia. Also, female athletes in sports such as rowing (where competition is organized by weight classes) are at high risk for developing a ‘female athlete triad,’ consisting of eating disorders such as anorexia, combined with loss of menstruation and a loss of bone mass that may cause osteoporosis later in life. The loss of menstruation resulting from overexercise has been attributed to the depletion of the body’s estrogen.Many anorexics also suffer from a related condition called bulimia,although bulimia can also occur independently of anorexia. Bulimia is characterized by occasional binge eating of everything in sight, usually including large quantities of high-calorie ‘forbidden’ foods, in total disregard of any concept of a balanced diet. Immediately after a binge, bulimics typically force themselves to vomit or else purge themselves with an overdose of a laxative. Both the binge and the purge are usually done in secret; bulimics (like anorexics) become extremely skillful at hiding their condition from others. Persistent bulimia can lead to ulcers and other problems of the digestive tract, and also to chemical erosion of the teeth from the frequent contact of the teeth with the acidic secretions of the stomach. Bulimia occurs in both sexes, but more often in women. Bulimia is especially common among educated women who have easy access to unrestricted amounts of food, a situation common on many college campuses.StarvationAround the world, more people die each year of starvation than of any single disease or other preventable cause. Death by starvation occurs primarily in poor countries, but it also occurs in pockets of poverty within wealthier nations. The immediate cause of death by starvation is usually inadequate caloric intake. In populations with very low caloric intake, even a small or temporary interruption in the food supply can lead to mass starvation: just one bad crop, or political disruption that prevents the planting or harvesting of the crop, can have severe consequences.Inadequate caloric intake can also result in protein deficiencies that take several forms, including both low total protein and low levels of particular amino acids. If protein intake is inadequate for either reason, a protein deficiency called kwashiorkor develops. Kwashiorkor occurs when carbohydrate intake is adequate but protein intake is not.In all organisms, cells and proteins are constantly being broken down, and in a healthy, adequately nourished body, they are constantly being replenished. When protein intake is insufficient for this replenishment to occur, there is considerable loss of muscle tissue, and the death of many cells releases numerous dissolved ions into the surrounding tissue. These ions retain water and contribute to tissue swelling (edema) that makes the loss of muscle tissue harder to see. Children suffering from kwashiorkor have swollen abdomens, a fact often noticed in photographs from protein-deficient areas. Their large bellies conceal the fact that these children are actually starving to death.If protein intake is inadequate and carbohydrate intake is also inadequate, the combined deficiency produces a condition called marasmus, in which the body slowly digests its own tissues and wastes away. When carbohydrate is not available as an energy source, amino acids are used to produce energy. Because amino acids are not stored except in the form of the body’s structural and functional proteins, the use of amino acids for metabolic energy degrades these proteins. Once the body’s muscle mass falls below a certain minimum, marasmus is always fatal.Ecological factors contributing to poor dietsMalnutrition is recognized as a worldwide disease with regional differences in its cause but with similar outcomes everywhere. Here we take Africa as an example, although many other examples exist. Many populations in Africa experience either chronic or periodic protein deficiency; Africa has therefore been described as a protein-starved continent. Fresh vegetables are widely available, so diets are high in fiber and most vitamins. Vegetables (including legumes) can fill nearly all of a population’s nutritional needs as long as supplies are adequate and as long as some form of nutritionally complete protein is obtainable from animal sources (including fish) or from a combination of plant proteins. There are lakes and rivers where fishing provides adequate protein resources, and there are cattle-herding groups, such as the Masai and Fulani, who can meet their protein needs from their animals. Across most of the continent, however, animal protein sources are not readily available, and the supplies of grains that could offer protein by amino acid balancing are not always adequate.Grain supplies are inadequate owing to a combination of ecological and social factors. Tsetse flies, which spread blood-borne diseases, have made much of the land uninhabitable to most domestic animals. This not only limits the availability of meat proteins, but also limits the supply of draft animals that can pull plows and till the soil. Tractors and fuel are too expensive for most farmers in Africa, and many places are either too dry or too wet to support agriculture. The world’s largest desert, the Sahara, occupies most of Africa’s northern half; other deserts exist in Somalia and Namibia. Most of these deserts, including the vast Sahara, are growing larger each year as animals such as sheep and goats overgraze and destroy the plants on the desert fringes, a process known as desertification (see Chapter 18, pp. 669–672). In other parts, high rainfallleaches important minerals from the soil, leaving soils deficient in the minerals necessary for plant growth (see Chapter 11, p. 373 and pp. 384–386). Rice, wheat, and most other grains grow rather poorly in many African soils. Some success has been achieved with millet and corn (maize), but raising a sufficient quantity and variety of grains to provide complete protein is difficult. In most places in Africa, populations can maintain adequate nutrition in years when there are ample harvests and efficient distribution. Unfortunately, these two conditions are not always met. Protein deficiencies are made worse by political and military upheavals that drive people from their farms or that prevent the planting, harvesting and distribution of crops. Protein starvation (marasmus and kwashiorkor) is all too common, particularly among children.Effects of poverty and war on healthClimatic, economic, and political factors all contribute to the unequal production and unequal distribution of food across the planet. Poverty exists in all nations of the world. Many populations are marginally nourished and are therefore more vulnerable to a year of drought or a bad harvest, but malnutrition exists in every part of the globe, especially among the poor. Even in regions in which nourishment is usually adequate, people can become undernourished because of the disruptions of life associated with war.Wartime starvation. The effects of starvation on humans have been studied retrospectively in people who were, at an earlier time, subjected to starvation by war. Such a study on the short-term and long-term effects of starvation was conducted by using the birth records of infants born in the Netherlands in the winter of 1944–1945, when many people in certain cities experienced starvation. The food shortages varied from city to city, but the other effects of war were equal across the country. It was found that when food rations dropped below a threshold level, fertility in the population decreased and the decrease was greatest among people in the lower classes. Fetuses carried by women who experienced starvation in the first trimester had a higher rate of abnormal development of the central nervous system. Maternal undernourishment in that period also carried forward to premature births, very low birth weight, and an increase in infant death rate immediately after birth. Maternal undernourishment in the third trimester produced the greatest increase in the infant death rate in the three months after birth. Brain cells were depleted in infants who died. Among survivors, however, undernourishment in infancy was not correlated with long-term effects on mental development when males were tested at age 18. Other retrospective studies have found similar results.Long-term effects of childhood undernutrition. There are several indications that undernutrition during childhood decreases brain development and capacity. Infants who died of kwashiorkor or marasmus had less DNA, protein, and lipid in their brain cells compared with infants who died at similar ages of causes not related to nutrition. Evidence suggests that both the severity and the length of the period of malnutrition affect intellectual development. Iron deficiency, particularly in the early years of life, can also impair mental functions.Malnutrition can also result from children’s failure to eat properly because of a depressed mental state. Malnutrition of this type is called ‘failure to thrive.’ Infants must learn that their needs will be met, and this learned capacity is termed ‘basic trust.’ When circumstances are such that a child is not regularly fed and nurtured, it fails to develop trust. Loss of a caregiver or a diminution or loss of nurturing care can create depression in infants, who then lose trust and become malnourished. Medical intervention cannot rescue the child unless a trusting relationship is established. Adults recover their physical and mental capacities if they are rescued from starvation. For children, however, nutritional replacement will not lead to full recovery unless emotional and psychological support is also provided. The recovery of children from famine requires much more than food.Micronutrient malnutritionMalnutrition can still exist when total caloric intake is sufficient or even when it is excessive. Because the roles of micronutrients include the proper functioning of enzymes, micronutrient deficiencies prevent the proper utilization of other foods. As we saw earlier, mineral deficiencies can result when diets are restricted to those foods grown in mineral deficient soils. Diets that include only a few types of foods, particularly processed ‘junk foods,’ may be lacking in necessary micronutrients. It is for this reason that Japanese children are encouraged to “eat at least 100 different foods each week.” Limited incomes, limited mobility, and limited availability of fresh foods all make this goal difficult to achieve and generally make nutritional problems worse. Micronutrient malnutrition may be a danger that is overlooked among people who lose interest in eating, including elderly people, people with chronic diseases including cancer, and people who have mental illnesses such as depression. Some elderly people may also forget what they have or have not eaten. Thus, many people need more than just food in order to be properly nourished.THOUGHT QUESTIONSThink about the definition of obesity as a weight 20% or more above the ideal weight for a person’s sex and height. What is meant by ‘ideal?’ Who sets these ‘ideals?’ Are there cultural differences in what is considered ‘ideal?’ How do cultural definitions of ‘ideal’ relate to biological definitions?Why do you suppose anorexia occurs only among well-fed populations, and never among the poor or in times of famine?What does this imply about the possible causes of the condition?Will efforts aimed at improving nutrition in people with various forms of malnourishment be readily accepted by the people they are meant to help? What factors determine acceptance?If sufficient food can be produced, will every person have good nutrition? Why or why not?Why might starvation have greater longterm effects in children than in adults?Concluding RemarksDuring the first half of the twentieth century, vitamin deficiencies were major public health concerns. Vitamin and mineral deficiencies can lead to various deficiency diseases, birth defects, or neurological damage. Nutritional deficiencies and deficiency diseases have declined since then in the industrial world, the results of better eating habits, more varied diets, and vitamin-fortified foods. Greater interest now centers on whether certain foods can promote good health and reduce the risks of chronic diseases. Since the 1960s, public health officials and nutritionists have increasingly turned their attention to heart disease, stroke, cancer, and chronic health problems such as obesity and high blood pressure that can influence the risks for these fatal diseases. Heart disease is the number one cause of death in many industrialized countries and is significantly associated with a diet that is too high in fat, particularly saturated fats.Malnutrition still exists, however, and it can take many forms. Inadequate caloric intake can result from crop failures, from poverty, or fromSummary to Chapter 10 363eating disorders. Poverty and war usually worsen nutrition and contribute to stress among civilians. Adequate nutrition depends on getting all the necessary nutrients without taking in too much of any one of them. Much of the world’s population gets inadequate food and inadequate protein. In many industrialized countries, problems are caused instead by high-fat diets with inadequate fiber. The best way to avoid both types of problems is to eat a varied diet while keeping fat intake low. Sensible eating habits such as these are important for good health. If we want to promote health for ourselves, our families, and the rest of humankind, then a very important step is ensuring that each person has an adequate and balanced diet.Chapter SummaryDigestion is a process in which materials consumed as food are broken down into substances that the body can absorb and then use. Digestion consists of chemical digestion with the aid of enzymes, and mechanical digestion.The macronutrients are the major sources for energy, measured in kilocalories, and including carbohydrates, lipids (fats and oils), and proteins. Lipids are also needed for the formation of cell membranes, and proteins are needed as enzymes, receptors, and membrane transporters. Complete proteins have all the amino acids needed in human nutrition. Proteins are digested and used until one of the needed amino acids, called the limiting amino acid, is depleted, after which the remaining protein is used as an energy source in the manner of carbohydrates.Molecules or parts of molecules may be either polar and thus stable in contact with water or else nonpolar and thus water-avoiding.Digested food enters cells by passive diffusion, facilitated diffusion, active transport, or endocytosis. Diffusion always acts along a concentration gradient, from a place of higher concentration to a place of lower concentration; active transport always operates against such a concentration gradient. Concentration gradients can serve as a form of energy storage.Cellular energy is derived in the mitochondria by oxidation reactions in the Krebs cycle and electron transport to form ATP.Material that the body cannot absorb constitutes fiber.Micronutrients (vitamins and minerals, including electrolytes) are needed for good health.Epidemiology is the statistical study of diseases and risks in large populations. Data from epidemiology can help to provide evidence for certain health risks and benefits, even when the mechanisms of action are not known.Good nutrition reduces such chronic conditions as high blood pressure and obesity, and lowers the risks for cardiovascular disease and certain cancers.Malnutrition can result from inadequate food, inadequate protein, or vitamin and mineral deficiencies. Eating disorders such as anorexia and bulimia can lead to malnutrition.CONNECTIONS TO OTHER CHAPTERSChapter 3 Some genetic differences exist in the body’s ability to digest certain substances (as in phenylketonuria) or to use certain nutrients after their absorption (as in diabetes).Chapter 7 Nutritional requirements may differ among human populations for various inherited and environmental reasons.Chapter 9 Unchecked population growth puts more people at risk for malnutrition.Chapter 11 Crop improvements may help to alleviate starvation in many populations.Chapter 12 Certain cancers have frequencies that vary according to diet: high-fat diets promote certain cancers, whereas high-fiber diets lower many cancer risks.Chapter 15 Poor nutritional status impairs the immune system.Chapter 16 People with HIV infection stay less sick if they have good nutrition, but appetite is often suppressed (and nutrition suffers) as AIDS progresses.Chapter 18 Biodiversity is threatened by the need to clear more land for farming to feed the world’s population. Developing and conserving better and more varied crop plants will feed more people and support greater biodiversity at the same time.PRACTICE QUESTIONSExplain the differences between chemical digestion and mechanical digestion.How many times greater is the hydrogen ion concentration in stomach acid than in blood?What makes a molecule polar? What makes a molecule nonpolar? Can some molecules be both polar and nonpolar?What kinds of food molecules can supply precursors to the Krebs cycle?What type of transport is used to bring glucose into a cell?What hormone regulates the uptake of glucose by cells?What type of transport brings lipids into cells? How are nonpolar lipids able to travel through the blood to get to cells?How does atherosclerosis result in an increase in blood pressure?What is the HDL:LDL ratio and why is it important?What are the functions of cholesterol in the human body?Which food molecules produce the most ATP?Where in the cell is ATP produced?What are some of the functions of the watersoluble vitamins in the body?How is an electrolyte different from other mineral micronutrients? What are some of the functions of each in the body?Which can lead to health problems: vitamin deficiencies or vitamin megadoses?IssuesWhat is plant science?How has plant science changed the world?Can plant science feed the world?Why is the ‘law of unintended consequences’ so important?Are genetically engineered plants different from other plants?Photosynthesis (autotrophs, lightdependent reactions, dark reactions)
Osmosis
Nitrogen cycle Structure and function of plants (tissues, water transport, gas exchange) Ecosystems (trophic levels: producers, consumers, decomposers; soil; sustainable agriculture; pest control; integrated pest management) Limiting factors (fertilizers, irrigation) Plant genetic engineering Chapter 11 overview Plants capture energy from the sun and make many useful products Plant products that are useful to humans Photosynthesis Nitrogen travels through the world's ecosystems Nitrogen for plant products Mutualistic relationships Plants living in nitrogen-poor soils Plants use specialized tissues and transport mechanisms Tissue specialization in plants Water transport in plants Crop productivity can be increased by overcoming various constraints Fertilizers Soil improvement and conservation Irrigation Hydroponics Chemical pest control Integrated protection a of crops Crop yields can be increased Plant genomes can be amplified Changing plant genomes is nothing new Changing plant varieties through genetic engineering Use of transgenic plants Ants Risks and concerns 365366 Plants for nutrition Global Hunger, famine and malnutrition are endemic in many parts of the world (see Chapter 10). The rapid increase in the world's population (see Chapter 9) has exacerbated these problems. Since all the food we eat comes directly or indirectly from plants, any attempt to produce adequate food for the world's growing population must focus on producing food through plants. However, the cultivated area has its geographical limits, and expanding these limits has very high biological costs in terms of destruction of natural ecosystems (see Chapter 18). Another way to increase agricultural production is to increase the yields or nutrient levels of agricultural species through techniques such as soil improvement, the use of fertilizers and advanced irrigation techniques, pest control, and the use of different crops. or new genetic varieties of crops. In this chapter we will focus on the production of food by plants, since that is where most of our food comes from. Plants are essential to all life on Earth. In addition to food, plants also provide the oxygen that humans and other organisms breathe. Without plants, most other life forms would soon become extinct. Plants are the richest source of energy in the world. Globally, the amount of energy produced by plants is about 6 ¥1017 kilocalories per year (abbreviated kcal/year), or the equivalent of a sugar cube 5 km (or 3 miles) on a side, and we are exceeding quickly this energy resource. . This chapter looks at how plants provide energy to other organisms and how, by applying this knowledge, humans can learn to farm more and more efficiently. Plants capture energy from the sun and produce many useful products. Plants are a kingdom of living organisms that have eukaryotic cells that contain specialized structures to capture energy from sunlight. Plants are essential to life on Earth because they don't simply consume all the light energy they capture; They convert much of this light energy into a form that can be used by organisms that cannot use light energy directly. And plants do even more: In the process of building and maintaining their own bodies, plants produce products that satisfy many of the needs of other organisms. This section looks at exactly how plants capture and convert energy from light, the ultimate source of the plant products we depend on. Plant products are mainly consumed as food, that is, as a source of energy and nutrients (see Chapter 10). Many of these foods are carbohydrates (and some are oils) that plants have stored for their own use as energy sources at a later time. Agriculture, that is, the cultivation of plants for human consumption, is often regarded as the decisive achievement that also led to the rise of human civilization. The most important crops for the development of civilization were cereal grains (wheat, rice, corn, oats and others). Today, wheat, rice, corn, and potatoes provide more food than all other crops combined. Of the nearly 250,000 known plant species, about 80,000 are edible to humans. However, only about 30 of these make up the most important crops. Humans also use plants as a source of beverages, flavors, fragrances, dyes, poisons, decorations, building materials, and medicines. Plant-based beverages include coffee, tea, cola, beer, wine, spirits, and many juices. Many plant parts are used as spices, fragrances, and flavorings, from barks like cinnamon, seeds like black pepper, and roots like ginger, to flowers and flower parts like cloves, saffron, and vanilla (Table 11.1). . Often an essential oil or other ingredient is pressed or extracted from the appropriate part of the plant and used in a concentrated form. Some of these extracts are used as fragrances or food ingredients; others are used as animal poisons. For example, native South Americans use roots that contain rotenone to help catch fish by temporarily paralyzing them. Rotenone is also used as a pesticide because it paralyzes and kills insects. Cassava, a tropical root, is the source of both an arrow poison and tapioca, a food that also serves as a thickening agent. Wood is a commercially important plant product that is used worldwide for fuel and as a construction material in the form of wood. The history of human civilization would have been very different without spears, axes, pickaxes, boats, and many other items made primarily of wood. Paper and paper products are also made primarily of wood. Our modern arsenal of prescription drugs is largely derived from plant products, much of it from the tropics (Table 11.2). Other drugs, such as aspirin, were originally derived from plants. .RoseÄtherisches ÖlKLASSE MONOCOTYLEDONAELiliengewächseAllium sativumKnoblauchknollenIrisgewächseCrocus sativusSafranBlütenblätterOrchideengewächseVanille spp. Weidenrinde oder teeähnliche Aufgüsse aus Weidenrinde wurden unter anderem von den Griechen und amerikanischen Ureinwohnern jahrhundertelang zur Behandlung von Schmerzen verwendet. Viele pflanzliche Arzneimittel werden weiterhin in vielen Teilen der Welt ve Photosynthese Plants use energy that they capture from the sun to produce energy-rich carbohydrates through a process called photosynthesis. You store carbohydrates for your own use. own use as a source of energy for a later time. When humans and other animals eat plants, they harvest some of that energy. Producers and collectors of energy. Organisms such as plants that can use light or other inorganic energy sources to make all of their own organic (carbonaceous) molecules from simpler molecules are called autotrophs. Most other organisms, like animals, are heterotrophs; they cannot make their own organic compounds from inorganic materials and are therefore absolutely dependent on organic compounds produced by plants and other autotrophs. Instead of harvesting energy from light, most heterotrophs use energy stored by other organisms, including plants, in the form of chemical bonds. Most autotrophs are also called producers because they produce compounds that can be used by other organisms, including ourselves. Most heterotrophs are consumers who must obtain their energy by eating other organisms. Plants are the ultimate source of dietary energy, not only for primary consumers who consume plants directly, but also for secondary and value consumers who consume other consumers. When organisms die, their complex organic molecules are broken down by other heterotrophs called decomposers; decomposition products can then be recycled and used by other living things. Energy enters the biological world as sunlight and alternately flows through the production, consumption, and decomposition of organisms (Figure 11.1). With each step, some energy is lost, converting it into forms that organisms cannot use. Most of this unusable energy escapes as heat. The heat loss would cause the process to run its course and come to a complete stop if new energy was not constantly supplied. The new energy for the living world is sunlight. Plants are essential to the global energy flowPLANTDRUGLATIN NAMECOMMON NAMENAMEUSEDigitalis purpureaPurple foxglovedigitalisstrengthens heart contractionsRauwolfia serpentiaIndia snakerootreserpinelowers blood pressureAtropa belladonnaDeadly nightshadeatropineblocks neurotransmitters, antispasmodicbelladonnablocks neurotransmitters, antispasmodicDatura spp.Jimson weed (thorn apple)scopalaminesedative, controls nauseaPapaver somniferumOpium poppiescodeinecough suppressant, pain killermorphinepain killerCinchon ledgerianaCinchona tree barkquininemalaria preventionCatharanthus roseusMadagascar Rose PeriwinkleVinBlastinCancer ChemotherapyVincristineCancer ChemotherapyTaxus brevifoliaPacific Yew TaxolCancer Chemotherapybecause they are the primary means by which light energy is captured and converted into forms that other organisms can use. energy and pigments. Through the process of photosynthesis, plants obtain energy from sunlight and use that energy to produce carbohydrates (sugars and starches; see Chapter 10, pp. 328–329) from atmospheric carbon dioxide and water. The general process can be summarized by the following equation: Light energy6 CO2+ 12 pattern2boss6H12o6O+6O2+ 6 patterns2Carbon Water Glucose Oxygen Water Dioxide (a sugar) Plants maintain the composition of the atmosphere by consuming carbon dioxide and releasing oxygen in return. Thus, they sustain the life of animals (including humans) by providing the oxygen we breathe. The capture of light energy for photosynthesis takes place in certain photosensitive molecules called pigments, the most important being chlorophyll. Each of these molecules absorbs some wavelengths of light and not others. Chlorophyll absorbs blue and red light, but not green light. The colors we see are reflected rather than absorbed, which is why so many living things appear green (Figure 11.2). In addition to chlorophyll, plants and other photosynthetic organisms have other pigments, such as carotenes and xanthophylls, which absorb light of other colors and pass the energy to chlorophyll. These pigments are useful for the organism because they allow it to use light energy of different wavelengths. Since certain light-absorbing pigments are only found in certain groups of photosynthetic organisms, the pigments are used to identify these groups and reconstruct their evolution. Figure 11.1 Energy flow through a biological system. The energy comes in the form of sunlight. Producers convert sunlight into chemical bond energy that can be used by other organisms, consumers. The energy trapped in the chemical bonds of dead producers and consumers is released by decaying organisms. Also, energy is lost as heat at each step, so more and more energy must constantly enter the system for the process to continue. Light of all wavelengths (colors) is received by the leaf Amount absorbed Leaf absorbs all wavelengths except green and yellow, which it reflects Absorption spectrum of sunlight for chlorophyll a (numbers show wavelengths wave in nanometers) we see the reflected light, this is what the green leaf looks like. For example, the similarity between the pigments of green algae, mosses, and vascular plants has been used to argue that mosses and vascular plants likely evolved from green algae (see Chapter 6). Leafy trees in temperate latitudes stop producing chlorophyll in autumn. In the absence of chlorophyll, the other pigments in the leaves become visible. These pigments absorb green and blue and reflect many other colors of light, resulting in the amazing rainbow of colors in the fall leaves (see Figure 1.1, pg. 5). In all photosynthetic organisms that have a eukaryotic cell structure (plants, including algae; see Chapter 6), photosynthetic pigments are contained in organelles called chloroplasts, located in the cells of the green parts, especially the leaves. The liquid interior of these chloroplasts contains lots of flattened membrane vesicles (Figure 11.3). Photosynthesis takes place along the membranes of these stacked vesicles (called thylakoids). Although most photosynthetic organisms are plants, there are also several photosynthetic species in the kingdom eubacteria, including some bacteria and all cyanobacteria. These simpler photosynthetic organisms have a prokaryotic cell structure (see Box 6.2, pp. 170-171) without internal membranes or chloroplasts, so photosynthesis in these organisms occurs along the cell's plasma membrane and in the cytoplasm. Photosynthetic prokaryotes (bacteria and cyanobacteria) and eukaryotes (diatoms, dinoflagellates, and others) fill our oceans with nutrients that can be used by other organisms. Photosynthesis takes place in two steps. The first stage consists of the reactions that take place on the membranes of the stacked vesicles; these require light energy and are therefore called light reactions. You can follow the steps of the light reactions in Figure 11.4. In step 1, photosynthetic pigments in the vesicle membrane capture light energy, represented by golden rays. The captured energy is used to split the water molecules into hydrogen and oxygen (step 2). The oxygen is released into the atmosphere (Step 3), where it is essential for oxygen-dependent organisms, including humans. Each hydrogen atom is further divided into a hydrogen ion (H+) and an electron (e–). Hydrogen ions are also called protons and are shown as gray circles in Figure 11.4. Hydrogen ions accumulate within the membranes of the stacked vesicles (step 4). Electrons are shown as blue circles and blue arrows in Figure 11.4. The electrons travel along a chain of electron transport proteins that are part of the vesicle membrane (step 5) and are ultimately the thylakoid vesicles of plant cells. Figure 11.3 Site of photosynthesis in plant cells. There are chloroplasts in plant cells. Each chloroplast contains stacks of thylakoids. Vesicular membrane and photosynthetic pigment membranes of chloroplasts, which are donated to a molecule called NADP+, forming NADPH (step 6). NADP+ is an energy-carrying molecule made in part from niacin, a vitamin discussed in Chapter 10 (pp. 337-338). Some of the electron transport proteins are ion pumps. These use part of the energy of the electrons to pump hydrogen ions to the stacked membranes (step 7) and thus form an ion gradient. As with other ion gradients, such as those that cross the membranes of mitochondria (see Chapter 10, pp. 350-351), the hydrogen ion gradient stores energy. The stored energy is then used to fuel the synthesis of the high-energy ATP molecule (Step 8). The plant cell uses ATP for most biological activities that require an energy source, just as we saw in Chapter 10 for animal cells. In short, light energy captured in the light reactions of photosynthesis is converted into high-energy chemical bonds in NADPH and the Sun Figure 11.4 The light reactions of photosynthesis. Flows of energy, electrons, and hydrogen ions are shown, as well as the synthesis of ATP and NADPH, which contain high-energy photosynthetic pigments1. CURRENT Light energy flow of electrons Fuel transport of electrons plus H+ is pumped to H+6NADP++NADPHH+chemical bonds.PH+ ATP thylakoid vesicle _membrane eO 3OH There is water 25H+ H+4electron transport proteinsH+H+ 7H+ATP H+ H+ 8synthesize absorbed energy splits water into:OxygenH+Hydrogen ions_ Electrons Figure 11.5 Summary of photosynthetic reactions. ATP light energy. This stored energy, derived from light, is then used in the dark reactions that make up the rest of photosynthesis. Some of the energy in light is also inevitably converted to heat. Photosynthesis: dark reactions. The ATP and NADPH generated in the stacked membrane vesicles are not released from the chloroplasts; they move from these vesicles into the fluid surrounding the chloroplasts (see Figure 11.3). In this solar chloroplast fluid 12 H2O + 6 CO2 6 O2 + C6H12O6 + 6 H2O, ATP and NADPH are involved in the second of the two phases of photosynthesis. ATP provides energy and NADPH provides hydrogen for the synthesis of glucose (C6H12o6) from carbon dioxide (CO2), the carbon source12 H2O LIGHT REACTIONS6 O2ATPNADPHCO2 DARK REACTIONS C6H12O66 H2O and oxygen atoms. Since reactions using ATP and NADPH do not require light directly, they are called dark reactions. The net result of the dark reactions is that atmospheric carbon dioxide is "fixed" or incorporated into organic plant matter as glucose sugar. Figure 11.5 summarizes the general process of photosynthesis. Under most conditions, glucose is used immediately as an energy source in metabolism or is converted to sucrose, fructose, starch, or other carbohydrates (see Chapter 10, pp. 328-329) for long-term energy storage. term. If the plant later needs the energy at a time when photosynthesis is not possible, or in a non-photosynthetic part of the plant, substances stored in the plants can be converted back to glucose and broken down to provide energy. Table sugar is sucrose, the product stored in sugar cane and sugar beets. Starch is the storage product in potatoes and cereals. In addition to these carbohydrate storage molecules, many plants (including maize, palm, and most nuts) use oils (see Chapter 10, pp. 330–331) as storage products in their seeds; The energy stored in the seed is consumed when the seed germinates. The growth of the new plant depends on the energy of the seeds until enough new leaves are produced to carry out photosynthesis on their own. Are plants that are useful to humans more valuable than those that are not? Is utility the only criteria for making something worthwhile? Is economic value the only way to measure value? What might be some of the other possibilities? How would you measure them? How are large plants (eg, trees) used by other plants? How are plants used by animals? List as many uses as possible. Do animals have molecules that can absorb light energy? Where could you expect them? Some producer organisms are autotrophs, but are all producers autotrophs? Can a consumer organism also be considered a producer organism if it is eaten by another consumer organism? The sun is a free and renewable source of energy. Man cannot photosynthesize, but in what other ways has he harnessed the sun's energy? What other uses can be developed in the future? Nitrogen Cycles in the World's Ecosystems An ecosystem includes all the species that live and interact together and all the physical resources (including water, soil, and atmosphere) with which they interact. Materials are naturally recycled in ecosystems and each chemical element has its own cyclical pattern. Some of these patterns are simple. For example, oxygen is combined with organic compounds in all organisms (for example, during cellular respiration, described in Chapter 10) and released to the atmosphere during photosynthesis. Carbon is incorporated into organic compounds during photosynthesis and released to the atmosphere as CO2as the end product of respiration and decomposition. Of the various chemical elements that plants need to make their essential biological molecules, carbon can be obtained from atmospheric carbon dioxide during photosynthesis, and water can serve as a source of hydrogen and oxygen, as well as dissolved ions. However, nitrogen follows a more complex cycle. Nitrogen for plant products In addition to the molecules produced as a result of photosynthesis, plants also need to synthesize nucleotides for DNA and RNA and amino acids for proteins. The synthesis of these and other molecules requires nitrogen. Amino acids can be made from simpler compounds by adding an amino group (-NH2🇧🇷 The amino group can be supplied from soluble ammonium compounds (containing the NH+ ion). Amino groups can also be transferred from one amino acid to another. Once the nitrogenous amino acids have been synthesized, they can be used to build proteins. Amino acids also serve as precursors to all other nitrogenous compounds needed by the plant, including DNA and RNA, vitamins, plant hormones, and dyes. Nitrate: a limiting nutrient. Although plants are a source of amino groups (-NH2) to help form amino acids and proteins, most plants cannot absorb NH+ ions directly. Instead, they get their nitrogen from the soil as dissolved nitrates (NO - ions) or nitrites (NO - ions), which they then convert to ammonia (NH3🇧🇷 Ammonia reacts with water to form ammonium hydroxi