Genomic signatures of selection at linked sites: unifying the disparity among species

Abstract

Population genetics theory supplies powerful predictions about how natural selection interacts with genetic linkage to sculpt the genomic landscape of nucleotide polymorphism. Both the spread of beneficial mutations and the removal of deleterious mutations act to depress polymorphism levels, especially in low-recombination regions. However, empiricists have documented extreme disparities among species. Here we characterize the dominant features that could drive differences in linked selection among species--including roles for selective sweeps being 'hard' or 'soft'--and the concealing effects of demography and confounding genomic variables. We advocate targeted studies of closely related species to unify our understanding of how selection and linkage interact to shape genome evolution.

Figure 1. A hypothetical chromosome exhibiting a ‘selection at linked sites’ pattern

Given the hypothetical recombination rate profile across the chromosome (top panel) and random variation in mutation rate, reflected in divergence at unconstrained sites (blue points, middle panel), measures of neutral polymorphism at unconstrained sites are predicted by recurrent genetic hitchhiking and background selection to be lower in chromosomal regions with lower average recombination rates (red points, middle panel). Recurrent positive or negative selection would yield a positive association between polymorphism and recombination rate (bottom panel). These hypothetical data were generated assuming background selection, but recurrent hard sweeps would yield a qualitatively similar pattern.

Figure 2. Modes of selection on linked genetic variation and factors affecting them

A | In the top two panel rows, horizontal lines represent haplotypes in a population at a particular genomic locus, with distinct colours representing different genetic backgrounds (compared to well-mixed reference genetic backgrounds indicated in blue). A hard sweep (Aa) involves the fixation of a single new beneficial mutation, whereas a soft sweep (Ab) involves fixation of selectively equivalent alleles that occur at intermediate frequency (i.e. on differing genetic backgrounds) in the population at the onset of selection. Adaptation by polygenic selection (Ac) causes an increase in the frequency of alleles at many loci, but selection does not necessarily drive fixation at any given locus (i.e. multiple partial sweeps). Background selection (Ad) eliminates deleterious mutations and the genetic backgrounds linked to them. Beneficial alleles are represented by circles and stars represent deleterious alleles. The chromosome segment represents a region with a uniform rate of recombination. Dotted lines in the bottom row of panels represent the equilibrium expectation for neutral polymorphism; solid curves show qualitative patterns of neutral polymorphism across the chromosome region. B Differences among species in a broad range of factors could vary the strength of observed signatures of selection at linked sites as caused by recurrent genetic hitchhiking or background selection. Arrows indicate factors associated with recombination (red), selection (blue) and population demography (purple) that tend to exacerbate the effects of linked selection; bars indicate mitigating factors. This diagram is meant as a general summary, as the details of parameter values can change the influence of some exacerbating and mitigating factors.

Figure 3. Taxonomic support for different signatures of selection at linked sites

Species differ in their support for how selection and recombination interact to modulate patterns of molecular evolution. Summary of species signatures of linked selection in Table 1; a given species may be included in multiple categories in the figure. Theory predicts recurrent genetic hitchhiking (RHH) to generate positive correlations of recombination rate with neutral polymorphism, the site frequency spectrum, and dN. Background selection (BGS) also is predicted to yield positive correlations of recombination rate with neutral polymorphism.