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Modern Genetic Analysis Chapter 17. Population and Evolutionary Genetics
A Synthesis of Forces

The various forces of breeding structure, mutation, migration, and selection are all acting simultaneously in populations. We need to consider how these forces, operating together, mold the genetic composition of populations to produce both variation within local populations and differences between them.

Variation and Divergence of Populations

The genetic variation within and between populations is a result of the interplay of the various evolutionary forces (Figure 17-18). Generally, as Table 17-8 shows, forces that increase or maintain variation within populations prevent the differentiation of populations from each other, whereas the divergence of populations is a result of forces that make each population homozygous. Thus, random drift (or inbreeding) produces homozygosity while causing different populations to diverge. This divergence and homozygosity are counteracted by the constant flux of mutation and the migration between localities, which introduce variation into the populations again and tend to make them more like each other.

The effects of selection are more variable. Directional selection pushes a population toward homo-zygosity, rejecting most new mutations as they are introduced but occasionally (if the mutation is advantageous) spreading a new allele through the population to create a new homozygous state. Whether such directional selection promotes differentiation of populations depends on the environment and on chance events. Two populations living in very similar environments may be kept genetically similar by directional selection, but, if there are environmental differences, selection may direct the populations toward different compositions.

A particular case of interest, especially in human populations, is the interaction between mutation and directional selection in a very large population. New deleterious mutations are constantly arising spontaneously or as the result of the action of mutagens. These mutations may be completely recessive or partly dominant. Selection removes them from the population, but there will be an equilibrium between their appearance and removal.

The general expression for this equilibrium is that the frequency of the deleterious allele at equilibrium depends on the ratio of the mutation rate, m , to the intensity of selection, s, against the deleterious genotype. For a completely recessive deleterious allele whose fitness in homozygous state is 1 s, the equilibrium frequency is

These results are shown in detail in Genetics in Process 17-8. So, for example, a recessive lethal (s = 1) mutating at the rate of µ = 106 will have an equilibrium frequency of 103. Indeed, if we knew that a gene was a recessive lethal and had no heterozygous effects, we could estimate its mutation rate as the square of the allelic frequency. But the basis for such calculations must be firm. Sickle-cell anemia was once thought to be a recessive lethal with no heterozygous effects, which led to an estimated mutation rate in Africa of 0.1 for this locus.

A similar result can be obtained for a deleterious gene with some effect in heterozyotes. If we let the fitnesses be WA/A = 1.0, WA/a = 1 bs, and Wa/a = 1 s for a partly dominant gene, where h is the degree of dominance of the deleterious allele, then a similar calculation gives us

Thus, if µ = 106 and the lethal is not totally recessive but has a 5 percent deleterious effect in heterozygotes (s = 1.0, b = 0.05), then

which is smaller by two orders of magnitude than the equilibrium frequency for the purely recessive case. In general, then, we can expect deleterious, completely recessive genes to have frequencies much higher than those of partly dominant genes.

Selection favoring heterozygotes (balancing selection) will, for the most part, maintain more or less similar polymorphisms in different populations. However, again, if the environments are different enough between them, then the populations will show some divergence. The opposite of balancing selection is selection against heterozygotes, which produces unstable equilibria. Such selection will cause homozygosity and divergence between populations.

The Exploration of Adaptive Peaks

Random and selective forces should not be thought of as simple antagonists. Random drift may counteract the force of selection, but it can enhance it as well. The outcome of the evolutionary process is a result of the simultaneous operation of these two forces. Figure 17-19 illustrates these possibilities. Note that there are multiple adaptive peaks in this landscape. Because of random drift, a population under selection does not ascend an adaptive peak smoothly. Instead, it takes an erratic course in the field of gene frequencies, like an oxygen-starved mountain climber. Pathway I shows a population history where adaptation has failed. The random fluctuations of gene frequency were sufficiently great that the population by chance became fixed at an unfit genotype. In any population, some proportion of loci are fixed at a selectively unfavorable allele because the intensity of selection is insufficient to overcome the random drift to fixation. The existence of multiple adaptive peaks and the random fixation of less fit alleles are integral features of the evolutionary process. Natural selection cannot be relied on to produce the best of all possible worlds.

Pathway II in Figure 17-19, on the other hand, shows how random drift may improve adaptation. The population was originally in the sphere of influence of the lower adaptive peak; however, by random fluctuation in gene frequency, its composition passed over the adaptive saddle, and the population was captured by the higher, steeper adaptive peak. This passage from a lower to a higher adaptive stable state could never have occurred by selection in an infinite population, because, by selection alone,

© 1999 by W. H. Freeman and Company. All rights reserved.