Genetic linkage and natural selection

Abstract

The prevalence of recombination in eukaryotes poses one of the most puzzling questions in biology. The most compelling general explanation is that recombination facilitates selection by breaking down the negative associations generated by random drift (i.e. Hill-Robertson interference, HRI). I classify the effects of HRI owing to: deleterious mutation, balancing selection and selective sweeps on: neutral diversity, rates of adaptation and the mutation load. These effects are mediated primarily by the density of deleterious mutations and of selective sweeps. Sequence polymorphism and divergence suggest that these rates may be high enough to cause significant interference even in genomic regions of high recombination. However, neither seems able to generate enough variance in fitness to select strongly for high rates of recombination. It is plausible that spatial and temporal fluctuations in selection generate much more fitness variance, and hence selection for recombination, than can be explained by uniformly deleterious mutations or species-wide selective sweeps.

Figure 1.

Tight linkage exacerbates the increase in mutation load owing to drift, via the Hill–Robertson effect. The horizontal line shows the baseline mutation load in an infinite population (L = U), and the lower curve shows the diffusion approximation assuming free recombination. The dots show simulated values, for r = 0.5 (grey dots), 0.01 (black dots) and 0 (unfilled dots) between adjacent loci. Simulations are of haploid individuals with n = 100 loci on a linear chromosome; U = nμ = 1, s = 0.05; runs were for 5000 generations with a burn-in of 1000 generations. Mutation was symmetric, so that an equilibrium is reached even with complete linkage.

Figure 2.

An allele with advantage s = 2 × 10⁻⁵ declines over time as a result of random selective sweeps at linked loci. In this example, sweeps with strength S = 0.01 occur at a density Λ/R = 0.01 per Morgan, in a population of 2N = 10⁶. The expected rate of decline owing to linked sweeps is s_c = (2ΛS/R)(π²/3log[S/s]) ∼ 0.0001. However, the actual decline is highly variable.