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.

Author Summary

Comparisons of the human and chimpanzee genomes have revealed that the frequency of sequence differences between these species varies dramatically across the genome. Previously proposed explanations for this variation include a large ancestral population, variable mutation rates, or a complex speciation scenario in which humans and chimpanzees initially separated but then rehybridyzed several million years later. We consider, here, an alternate possibility; the action of selection to remove less-fit functional variants from a population has significantly reduced the frequency of “neutral” sequence differences at nearby sites. We identified sequences that are likely to be subject to natural selection because they are highly conserved across placental mammals and showed that neutral differences among five primate species are greatly depleted near such sequences. Applying a theoretical evolutionary model, we found that selection has played a greater role in shaping hominid genome evolution than has been appreciated and provides a better explanation for patterns of sequence differences than other hypotheses.