Widespread Genomic Signatures of Natural Selection in Hominid Evolution

Abstract

Selection acting on genomic functional elements can be detected by its indirect effects on population diversity at linked neutral sites. To illuminate the selective forces that shaped hominid evolution, we analyzed the genomic distributions of human polymorphisms and sequence differences among five primate species relative to the locations of conserved sequence features. Neutral sequence diversity in human and ancestral hominid populations is substantially reduced near such features, resulting in a surprisingly large genome average diversity reduction due to selection of 19–26% on the autosomes and 12–40% on the X chromosome. The overall trends are broadly consistent with “background selection” or hitchhiking in ancestral populations acting to remove deleterious variants. Average selection is much stronger on exonic (both protein-coding and untranslated) conserved features than non-exonic features. Long term selection, rather than complex speciation scenarios, explains the large intragenomic variation in human/chimpanzee divergence. Our analyses reveal a dominant role for selection in shaping genomic diversity and divergence patterns, clarify hominid evolution, and provide a baseline for investigating specific selective events.

A coalescent model of background selection with recombination, demography and variation in selection coefficients

“…The simulations reveal several patterns that are readily testable using DNA sequence polymorphisms: (1) a positive correlation between neutral diversity and recombination rates (Figure 3; Shapiro et al, 2007;Cai et al, 2009;Cutter and Choi, 2010); (2) a positive correlation between neutral diversity and the distance to regions subject to background selection (Figure 4b; McVicker et al, 2009); (3) a deficit of diversity in the middle of a selected region (Figures 3 and 4b; Comeron and Guthrie, 2005); (4) a negative correlation between the prevalence of singletons (or low-frequency variants) and recombination rates (Figure 3; Shapiro et al, 2007;Lohmueller et al, 2011); (5) a negative correlation between the prevalence of singletons and the distance to regions subject to background selection (Figure 4c; Lohmueller et al, 2011); (6) an excess of singletons in the middle of a selected region (Figures 3 and 4c). Encouragingly, these patterns exist in the presence of recent demographic changes (Figure 4; Supplementary Figures S1 to S3), suggesting that previous analyses based on these correlations are likely to be robust.…”

“…Therefore, it is essential to study background selection and understand how its interplay with other evolutionary forces such as demographic changes can shape genomewide patterns of diversity. The importance of this has been highlighted by several recent examinations of DNA sequence polymorphisms in humans (McVicker et al, 2009;Hernandez et al, 2011;Lohmueller et al, 2011), Caenorhabditis (Cutter and Choi, 2010) and rice (Flowers et al, 2012) whereby broad-scale patterns of variability have been found to be compatible with predictions of a background selection model. Furthermore, there is evidence that background selection may explain the observation that the ratio of silent DNA sequence diversity for X-linked loci to that for autosomal loci is approximately one in East African populations of Drosophila melanogaster, instead of the expected value of three quarters (Charlesworth, 2012b).…”

Ancestral polymorphisms inDrosophila pseudoobscuraandDrosophila miranda

“…This underestimates the total number of ancestral polymorphisms by a factor of about two, which may bias estimates of sequence divergence (Gillespie & Langley, 1979 ;Patterson et al, 2006;McVicker et al, 2009 ;Cutter & Choi, 2010). In addition, use of the fraction of unequivocally identified shared polymorphisms alone may underestimate the role of balancing selection, which has previously been reported to be limited in a human-chimpanzee study of shared polymorphisms (Asthana et al, 2005).…”

“…The presence of ancestral polymorphisms within a species, and their fixation subsequent to speciation, can contribute to divergence from a closely related species ; this influences estimates of rates of sequence evolution, and may also lead to incorrect inferences concerning phylogenetic relationships (e.g. Gillespie & Langley, 1979;Clark, 1997 ;Maddison, 1997 ;Arbogast et al, 2002 ;Hudson & Coyne, 2002;McVicker et al, 2009 ;Cutter & Choi, 2010). In addition, estimates of the abundance of ancestral polymorphisms provide a test for balancing selection, since an excess frequency of ancestral polymorphisms within a gene or genetic region, relative to the level that would be expected under neutrality, is a signature of long-term balancing selection (Wiuf et al, 2004 ;Asthana et al, 2005).…”

In silico phylogenomics using complete genomes: a case study on the evolution of hominoids

“…Despite this concern, McCormack et al (2012) suggested that selection may not adversely affect species tree inferences based on UCE loci due to increased rates of lineage sorting, a hypothesis that has received empirical corroboration . However, estimates of effective population sizes based on genomic regions around conserved loci under purifying selection are expected to be reduced relative to more distant regions where "neutral" loci may be found (McVicker et al 2009). The effects of selection may also adversely affect estimates of other population genetic parameters such as population divergences and gene flow.…”