n of gametic disequilibrium between a selected mutation and the alleles present at neighboring neutral nucletide sites. As natural selection drives a favorable mutation to high frequency in a population, the neutral alleles in gametic disequilibrium with the selected mutation also reach high frequency because they happened to be on the chromosome where the advantageous mutation initially occurred. This also results in a loss of polymorphism in the population for the neutral alleles, since only the one set of neutral alleles in gametic disequilibrium with the advantageous mutation remains in the population once the advantageous mutation approaches fixation by natural selection. Levels of polymorphism decrease in Fig. 8.22 as the advantageous mutation becomes more and more frequent in the population. The reduction in polymorphism caused by genetic hitchhiking is sometimes called a selective sweep because while an advantageous mutation and the neutral polymorphisms that are linked to it are swept to high frequency by natural selection, other neutral polymorphisms not in gametic disequilibrium with the selected site are swept out of the population at the same time. It is important to emphasize that the reduction in polymorphism seen in selective sweeps is an indirect consequence of natural selection since only the advantageous mutation itself has a selection coefficient that is not effectively zero.

Genetic hitch-hiking The process by which selectively neutral alleles increase or decrease in frequency due to their association with alleles that are under the influence of natural selection.

Selective sweep The reduction or elimination of polymorphism in a region of DNA sequence surrounding a site where a beneficial mutation has increased in frequency due to positive natural selection. The reduction of polymorphism is a result of gametic disequilibrium between a beneficial mutation and neighboring neutral sites that has not been broken down by recombination.

The genetic hitch-hiking and selective sweep process that leads to reduced polymorphism at nucleotide sites in gametic disequilibrium with selected sites can be thought of as analogous to genetic drift at neutral sites. Positive natural selection causes some linked sets of alleles in the population to reach fixation faster than under genetic drift alone, in the same fashion that a reduction in the effective population size or genetic bottleneck would decrease the average time to fixation for those neutral alleles that do reach fixation. Gillespie (2000, 2001) has termed the selective sweep process genetic draft because neutral mutations in gametic disequilibrium are like an unpowered glider, floating their way to fixation by riding along on the up-currents of increased probability of substitution caused by selection. Gillespie has shown that genetic draft is a stochastic process because the neutral mutations that do reach fixation do so by random association with selected mutations. Thus, natural selection on infrequent beneficial mutations causes finite random sampling from the pool of available neutral mutations even if the effective population size is infinite.

Because mitochondrial genomes do not experience recombination, genetic hitch-hiking has the potential to cause strong selective sweeps. Evidence for selective sweeps in animal mitochondrial genomes comes from a comparison of polymorphism measured by nuclear allozyme loci, nuclear DNA sequences, and mito-chondrial DNA sequences for a large sample of animal species (912, 417, and 1683 species, respectively). Using these data, Bazin et al. (2006) tested the neutral hypothesis that polymorphism for all three types of data should be correlated since each class of loci shares a similar effective population size. (Because mitochondrial genomes are haploid and uniparent-ally inherited, their effective population size is four times less than that of biparentally inherited nuclear loci.) Based on census population sizes, insects, echinoderms, and mollusks are expected to have larger effective population sizes than mammals, fish, reptiles, and birds. Neutral theory predicts that the taxa with larger effective population sizes should also have higher levels of polymorphism for the same loci. This neutral prediction is met for nuclear allozyme and DNA sequence data. Levels of polymorphism are higher for insects, echinoderms, and mollusks than for mammals, fish, reptiles, and birds. Levels of polymorphism estimated from the two types of nuclear loci are also highly correlated within each species. In contrast, levels of mitochondrial polymorphism were both low and nearly uniform across all the animal groups and did not show a correlation with levels of nuclear allozyme and DNA sequence polymorphism. This result can be explained by genetic hitch-hiking that has caused selective sweeps in the non-recombining mitochondrial genome.

In the extreme case of no recombination, an advantageous mutation can never become associated via recombination with other neutral alleles that exist in the population. But the absence of recombination is not necessary for selective sweeps to occur. When recombination does occur, selective sweeps will still happen as long as the increase in frequency of an advantageous mutation is rapid relative to the time that is required for recombination to break down the gametic disequilibrium between a new mutation and its neighboring sites. In genomes with recombination, we therefore expect that selective sweeps may impact only relatively small areas centered around the site where an advantageous mutation occurred. This is because recombination will happen more and more frequently as the distance from the site of an advantageous mutation grows larger. Only in the nucleotide sites relatively near the advantageous mutation will recombination be unlikely to occur, allowing gametic disequilibrium to persist for long enough for selection to make appreciable changes in the frequency of the advantageous mutation. We can also expect that stronger natural selection should lead to larger or more persistent areas of reduced polymorphism because an advantageous mutation will reach fixation faster, outpacing recombination that would distribute the advantageous mutation across chromosomes with different neutral mutations.

A common result from studies of genetic variation at numerous loci in natural Drosophila populations is that levels of polymorphism are positively correlated with rates of recombination (reviewed by Hudson 1994). The relationship between polymorphism and rates of recombination can be explained in several ways. A hypothesis consistent with selective neutrality is that the recombination rate at a locus is somehow related to its mutation rate. For example, the molecular processes that cause recombination might also cause point mutations. Another neutral hypothesis is that regions of low recombination might also have higher functional constraints and therefore lower neutral mutation rates. Recall that neutral theory predicts that levels of polymorphism and rates of divergence are correlated since both are ultimately products of the mutation rate. This leads to the prediction that both levels of polymorphism and divergence rates should correlate with the recombination rate if neutral processes explain the relationship between recombination and polymorphism at the Drosophila loci. Data to test this neutral hypothesis for the correlation between

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