Population genetics (zoology)

Population genetics is the description and analysis of genetic traits and their causative genes at the population level. Classical genetics concerns the rules of genetic transmission from parents to offspring, developmental genetics evaluates the role of genes in development, and molecular genetics considers the molecular basis of genetic phenomena. Population genetics uses information from all three fields and helps explain why populations are so variable, why some harmful traits are common, why most animals and plants reproduce sexually, how evolution works, why some animals are altruistic, and how new species form.

The Sources of Variability

Simple observation tells us that animals are highly variable. Dogs can be big or small. They may have curly, long, wiry, or hypoallergenic fur. Others are bred for specific tasks, like herding or retrieving, while a few are born with diseases or abnormalities. These differences in the same species are the results of various genes combined with environmental influences. Unless an animal is an identical twin, their genotype is unique to them. Population genetics studies the variability in these genotypes in a population and examines the sources and the forces that maintain it.

Variability can come from genetic mutations. For example, about one human child in ten thousand is born with dominant achondroplasia (short-legged dwarfism). Some children with the trait inherit the condition from an affected parent, but some are the result of a new mutation. Many mutations are deleterious and are eventually eliminated from the population by the lowered survival or fertility rates of those who have the mutation, but while they remain in the population, they add to its variability. Occasionally, a seemingly harmful mutation persists, like the hemoglobin beta gene (HBB) on chromosome 11 that causes sickle-cell anemiaa severe disease characterized by red blood cells that become sickle-shaped in certain laboratory tests. HBB is recessive, meaning that two copies are needed to produce the anemia, but the disease is very common in specific populations. Over 90 percent of individuals identified with this gene in America are non-Hispanic Black or African American. Although these genes have large and conspicuous effects, most mutations and the great bulk of genetic variability in the population are the result of a large number of genes with individually small effects, often detected only through statistics. The variability of quantitative traits such as size is due mainly to the cumulative action of many individual genes, each of which produces its small effect. The average size stays roughly constant from generation to generation because individuals who are too large or too small are at a disadvantage. However, such individuals continuously arise from new mutations.

The driving force in evolution is natural selection, that is, the differential survival and fertility of different genotypes. New mutations occur continuously. Most of these are harmful, although usually only mildly so, but a small minority are beneficial. The rules of Mendelian inheritance ensure that the genes are thoroughly scrambled every generation. Natural selection acts like a sieve, retaining those genes that produce favorable phenotypes in various combinations and rejecting others. Such a process, acting over eons of time, has produced the variety and specific adaptations that can be found throughout the animal kingdom.

The Forces Against Change

Although evolutionary progress is the result of natural selection, most selection does not accomplish any systematic change. Most selection is directed at maintaining the status quo—eliminating harmful mutations, keeping up with transitory changes in the environment, and eliminating statistical outliers (extremes of variation). Most of the time, evolutionary change is very slow.

In most populations, mating is essentially random in that mates do not choose each other because of the genes they carry. There are exceptions, of course, but for the most part, random mating can be assumed. This permits a great simplification known as the Hardy-Weinberg rule. This rule says that if the proportion of a certain gene, say A, in the population is p and of another, say a, is q, then the three genotypes AA, Aa, and aa appear in the proportions p², 2pq, and q², respectively. (p and q are fractions between zero and one.) This is a simple application of elementary probability and the binomial theorem. Furthermore, after a few generations of random mating, genotypes at different loci also equilibrate, which means that the frequency of a composite genotype is the product of the frequencies at the constituent loci. The reason that this is so useful is that the number of genotypes is enormous, but a population can be characterized by a much smaller number of gene frequencies.

Genotypes are transient, but genes may persist unchanged for many generations. This has led the great theorists of population genetics, J. B. S. Haldane and R. A. Fisher in England and Sewall Wright in the United States, to make the primary units the frequency of individual genes and develop theories around this concept, making free use of the simple consequences of random mating. Such a gene-centered view has been described by scholar Richard Dawkins as the “selfish gene.” A population can be thought of as a collection of genes, each of which maximzes its chance of being passed on to future generations. This causes the population to become better adapted because those genes that improve adaptation have the best chance of being perpetuated.

An extension of this notion is kin selection. The concept holds that, to the extent that behavior is determined by genes, individuals should be protective of close relatives because relatives share genes. The fact that brothers and sisters share half their genes should lead a brother to be half as concerned with his sister’s survival and reproduction as with his own. Evolutionists believe that altruistic behavior in various animals, including humans, is the result of kin selection. The degree of self-sacrifice to protect a close relative is proportional to the fraction of shared genes. Parents regularly make sacrifices for their children, and this is what evolutionary theory would predict.

One way populations depart from random mating is inbreedingthe mating of individuals more closely related than if they were randomly chosen. Related individuals share one or more ancestors; hence, an inbred individual may get two copies of an ancestral gene, one through each parent. In this way, inbreeding increases the proportion of homozygotes. Because many deleterious recessive genes are hidden in the population, inbreeding can have a harmful effect by making genes homozygous. Similarly, if the population is subdivided into local units, mating mostly within themselves, these local units will be more homozygous than if the entire population mated at random. Small subpopulations will be more subject to purely random fluctuations in gene frequencies known as random genetic drifts. Therefore, subdivisions of a population often differ significantly, particularly with respect to unimportant genes.

The Argument Against Average Effects

The gene-centered view of evolution is not always accepted. Some evolutionists believe that it is simplistic to view an individual as a bag of genes, each trying to perpetuate itself. They emphasize that genes often interact in complicated ways and that a theory that deals with only average gene effects is incomplete. Modern theories of evolution take such complications into account.

This different viewpoint has led to a major controversy in evolution, one that has not yet been settled. Wright emphasized that many well-adapted phenotypes depend on genes that interact in very specific ways; two or more genes may be individually harmfu, but when combined, produce a beneficial effect. He argued that selecting genes on the basis of average effects cannot produce such combined effects. He believed that a population subdivided into many partially isolated units provides an opportunity for such interactions. An individual subpopulation, by random drift, might chance upon such a happy gene combination, in which case, the whole population can be upgraded by migrants from this subpopulation. Whether evolutionary advance results from gene interactions in subpopulations, from mass selection in largely unstructured populations, or from a combination of both is a question that remains unresolved.

Population genetics theory, along with the techniques of molecular genetics, has greatly deepened our knowledge of historical evolution. Everyone is familiar with tree diagrams of common ancestry that show, for example, birds and mammals branching off from early ancestors. In the past, these had to be constructed using external phenotypes and fossils. These techniques for measuring the relatedness of different species and determining their ancestral relations have been replaced by DNA sequencing, which produces much surer results. It has long been suspected that genes can persist for very long evolutionary periods, changing slightly to perform new, often related, but sometimes quite different functions. This belief has been confirmed repeatedly by molecular analysis. The similarity of the DNA sequences between some plant and animal genes is so great as to leave no doubt that they were both derived from a common ancestral gene a billion or more years ago.

Neutral Mutation and the Benefits of Sexual Reproduction

Most gene mutations have very small effects, and the smaller the effect, the less likely it is to be noticed. Molecular techniques have enabled scientists to detect changes in DNA without regard to the traits they cause or whether they have any effect at all. The Japanese geneticist Motoo Kimura advanced the idea that most evolution at the DNA level is not the result of natural selection but simply the result of mutation and chance, a concept termed neutral mutation. In vertebrates, especially in mammals, most of the DNA has no known function. The functional genes make up a very small fraction of the total DNA. Many scientists believe that most DNA evolution outside the genes—and some within—is the result of changes that are so nearly neutral as to be determined by chance. How large a role random drift plays in the evolution of changes in functional proteins is not certain.

A few animals and a large number of plants reproduce asexually. Instead of reproducing by using eggs and sperm, the progeny are carbon copies of the parent. Asexual reproduction has obvious advantages. If females could reproduce without males, producing only female offspring like themselves, reproduction would be twice as efficient. However, despite its inherent inefficiency, sexual reproduction is the rule, undoubtedly because of the gene-scrambling process that sex produces. The ability of a species to produce and try out countless gene combinations confers an evolutionary advantage that outweighs the cost of males. Another advantage of gene scrambling is that it permits harmful mutations to be eliminated from the population in groups rather than individually.

Population genetics is also concerned with the processes by which new species arise. Scientists believe that a population somehow becomes divided into two or more isolated groups, separated perhaps by a river, mountain range, or other geographical barrier. Each group then follows its own separate evolutionary course, and the groups’ dissimilar environments accentuate their differences. Eventually, so many differences between the two groups evolve that they are no longer compatible. The products of interspecies crosses, or hybrids, often do not develop normally or are sterile (like the mule). Sometimes, the two species do not mate because they are so different.

Theory, Observation, and Experiment

Population genetics involves theory, observation, and experiment. Population genetics examines how genes are influenced by mutation, selection, population size, migration, and chance. Scientists develop mathematical models that embody these theories and compare the results obtained using the models with data from laboratory experiments or field observations. These genetic models have become more and more sophisticated to take into account complex gene interactions and increasingly realistic population structures. The models are further complicated by efforts to account for random processes. Often, the mathematical geneticist relies on computers to perform complex analyses and computations.

One of the simpler models, which makes the assumption that mating is random, is the Hardy-Weinberg principle, also called the Hardy-Weinberg equilibrium. If the proportion of gene A in the population is p and that of gene a is q, then the three genotypes AA, Aa, and aa appear in the proportions p², 2pq, and q², respectively. The proportion of Aa is 2pq rather than simply pq because this genotype represents two combinations, maternal A with paternal a and paternal A with maternal a. This principle can be used to predict the frequency of persons with malaria resistance from the incidence of sickle-cell anemia. If one-tenth of the genes are sickle-cell genes and the other nine-tenths are normal, the frequency of two genes coming together to produce an anemic child is 0.1 × 0.1, or 0.01. The frequency of those resistant to malaria, who have one normal and one sickle-cell gene, is 2 × 0.1 × 0.9, or 0.18. A slight extension of the calculation (using the rates of malaria infection and death from the disease) can be used to estimate the death rate from malaria. Another mathematical model can be formed based on the molecular genetics theory of neutral mutation. A neutral mutation, because it is not influenced by natural selection, has an expected rate of evolution that is equal to the mutation rate. Mathematical models embodying this theory are used to quantitatively predict what will happen in an experiment or what an observational study will find and act as a test of the theory. Neutral mutation theory is quite complicated and requires advanced mathematics.

Observational population genetics consists of studying animals and plants in nature. Evolution rates are inferred from the fossil record. Field observations can determine the frequency of genes in different geographical areas or environments. The frequency of self- and cross-pollination can often be observed directly. DNA analysis, which can detect relationships or alterations that are not visible, is used to support field observations. For example, molecular markers have been used to determine parentage and relationship. DNA analysis revealed that certain birds that do not reproduce but care for the progeny of others are, in fact, close relatives, consistent with kin selection theory. The so-called genomic revolution led to new scientific knowledge, methods, and technology that dramatically increased applied population genetics's predictive, diagnostic, and probative value. Sequencing entire genomes in the twenty-first century is not only possible but relatively inexpensive and quick.

Migration timing, evolutionary adaptations, disease susceptibility or resistance, and the diversity of an animal population can all be gathered from an animal's genome. This information can help inform conservationists and other wildlife experts on best practices, animal-environment interactions, and future trends.

Population genetics increasingly relies on experimentation. Plants and animals can be used to study the process of selection, but to save time and reduce costs, most laboratory experiments involve small, rapidly reproducing organisms such as the fruit fly, Drosophila. Some of the most sensitive selection experiments have involved the use of small bioreactors called chemostatsa container in which a steady inflow of nutrients, steady outflow of wastes, and excess population permit a population to maintain a stable number of rapidly growing organisms, usually bacteria. These permit very sensitive measurements of the effects of mutation. Evolutionary studies that would require eons if studied in large animals or even mice can be completed in a very short time.

Explaining, Quantifying, and Predicting Evolution

The greatest intellectual value of population genetics has been to provide a theory of evolution that is explanatory, quantitative, and predictive. Population genetics places knowledge of mutation, gene action, selection, inbreeding, and population structure in a unified framework. It brings together Charles Darwin’s theory of evolution by natural selection, Gregor Mendel’s laws of inheritance, and molecular genetics to create a coherent picture of how evolution occurs.

Population genetics has provided explanations for variability in a population, the prevalence of sexual rather than asexual reproduction, the origin of new species, and behavioral traits such as altruism. It has also provided an understanding of why some harmful diseases occur in the population. Population genetics is used in animal and plant breeding to create rational selection and genome modification programs for specific environments. Using quantitative models, the results of various selection schemes can be compared, and the best one can be chosen. This science is applicable to rebuilding ecosystems and for international food growth programs to choose or engineer the best plants for the environment where they will be planted to produce the most output.

A particularly telling example of population genetics predicting an outcome is the development of resistance to insecticides, herbicides, and antibiotics. As people increasingly used these products, the insects, weeds, and bacteria adapted and developed a resistance, rendering the products ineffective. New products had to be developed to replace them. The development of resistance represents evolution by natural selection that occurred over millions of years and continues in modern species. The most problematic area of resistance is antibiotics because some treatable diseases adapt and threaten to move beyond the ability of medicine to cure. A major challenge to ecologists, microbiologists, physicians, and population geneticists is how to deal with the increasingly difficult problem of disease-producing microorganisms resistant to antibiotics.

Principal Terms

Deoxyribonucleic Acid (DNA): The chemical basis of genes

Dominant: Requiring only one copy of a gene for expression of the trait

Gene: The unit of heredity; a short stretch of DNA encoding a specific product, usually protein

Genotype: The gene makeup of an individual

Inbreeding: The mating of individuals more closely related than the population average

Meiosis: The two cell divisions leading to egg or sperm, during which the genes from the two parents are mixed

Mutation: A sudden, unpredictable change in a gene

Phenotype: A trait or combination of traits, the result of the genotype and environment

Random Genetic Drift: The random change of gene frequencies because of chance, especially in small populations

Recessive: Requiring two copies of a gene for the trait to be expressed

Selection: Differential survival and reproduction rates of different genotypes

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