Academic journal article Genetics

Allele Frequency Distribution under Recurrent Selective Sweeps

Academic journal article Genetics

Allele Frequency Distribution under Recurrent Selective Sweeps

Article excerpt

ABSTRACT

The allele frequency of a neutral variant in a population is pushed either upward or downward by directional selection on a linked beneficial mutation ("selective sweeps"). DNA sequences sampled after the fixation of the beneficial allele thus contain an excess of rare neutral alleles. This study investigates the allele frequency distribution under selective sweep models using analytic approximation and simulation. First, given a single selective sweep at a fixed time, I derive an expression for the sampling probabilities of neutral mutants. This solution can be used to estimate the time of the fixation of a beneficial allele from sequence data. Next, I obtain an approximation to mean allele frequencies under recurrent selective sweeps. Under recurrent sweeps, the frequency spectrum is skewed toward rare alleles. However, the excess of high-frequency derived alleles, previously shown to be a signature of single selective sweeps, disappears with recurrent sweeps. It is shown that, using this approximation and multilocus polymorphism data, genome-wide parameters of directional selection can be estimated.

THE origin and spread of mutations that increase their carriers' reproductive success are fundamental processes of Darwinian evolution. In contrast to deleterious and neutral mutations, beneficial mutations in plants and animals occur too infrequently to be observed directly in laboratories. As a result, we know much less about beneficial mutations (positive selection) than about neutral or deleterious mutations (purifying selection) . Many basic facts about beneficial mutations-their rate, fitness effects, genomic locations, and molecular properties-remain unknown. Recent developments in population genetic theory, however, have suggested some promising approaches to obtaining these quantities. Given that beneficial mutations occur very rarely, basic information about them can be obtained only by inferring past evolutionary events of positive selection. As in other problems of evolutionary inference, the dominant approach is to search present-day sequence polymorphism and diversity for the footprint of past events, in this case, for the signature of genetic hitchhiking.

Genetic hitchhiking (or "selective sweeps") is the sudden loss of genetic variation at neutral loci when a new beneficial allele arises nearby and is fixed in the population (MAYNARD SMITH and HAIGH 1974; KAPLAN et al. 1989; STEPHAN et al. 1992; BARTON 2000). Recent selective sweeps are expected to generate specific patterns of sequence variation, including a local reduction of variation (KiM and STEPHAN 2002), a skew in the allele frequency distribution (BRAVERMAN et al. 1995; FAY and Wu 2000), and an increase in linkage disequilibrium (THOMSON 1977; PRZEWORSKI 2002; KIM and NIELSEN 2004). Developments of hitchhiking theory, along with the rapid increase of DNA sequence data, have led to the discovery of many episodes of recent positive selection in natural populations (for example, ENARD et al. 2002; CLARK et al. 2004; SCHLENKE and BEGUN 2004).

It is more difficult, however, to measure the cumulative effect of recurrent selective sweeps throughout the genome. The main effect of recurrent selective sweeps is to reduce the standing level of variation, which is well understood (KAPLAN et al. 1989; WIEHE and STEPHAN 1993; GILLESPIE 2000). In particular, since recombination reduces the hitchhiking effect, a positive correlation between local recombination rate and sequence diversity is predicted under recurrent sweeps. Such a correlation has been observed in Drosophila melanogaster (BEGUN and AQUADRO 1992) and was used to estimate the intensity of directional selection, áë., where á is the scaled selection coefficient and ë is the frequency of hitchhiking events (WiEHE and STEPHAN 1993; STEPHAN 1995; ANDOLFATTO 2001). However, this calculation assumes that selective sweeps alone create the correlation between recombination and genetic variation. …

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