The impact of genetic adaptation on chimpanzee subspecies differentiation

Chimpanzees, humans’ closest relatives, are in danger of extinction. Aside from direct human impacts such as hunting and habitat destruction, a key threat is transmissible disease. As humans continue to encroach upon their habitats, which shrink in size and grow in density, the risk of inter-population and cross-species viral transmission increases, a point dramatically made in the reverse with the global HIV/AIDS pandemic. Inhabiting central Africa, the four subspecies of chimpanzees differ in demographic history and geographical range, and are likely differentially adapted to their particular local environments. To quantitatively explore genetic adaptation, we investigated the genic enrichment for SNPs highly differentiated between chimpanzee subspecies. Previous analyses of such patterns in human populations exhibited limited evidence of adaptation. In contrast, chimpanzees show evidence of recent positive selection, with differences among subspecies. Specifically, we observe strong evidence of recent selection in eastern chimpanzees, with highly differentiated SNPs being uniquely enriched in genic sites in a way that is expected under recent adaptation but not under neutral evolution or background selection. These sites are enriched for genes involved in immune responses to pathogens, and for genes inferred to differentiate the immune response to infection by simian immunodeficiency virus (SIV) in natural vs. non-natural host species. Conversely, central chimpanzees exhibit an enrichment of signatures of positive selection only at cytokine receptors, due to selective sweeps in CCR3, CCR9 and CXCR6 –paralogs of CCR5 and CXCR4, the two major receptors utilized by HIV to enter human cells. Thus, our results suggest that positive selection has contributed to the genetic and phenotypic differentiation of chimpanzee subspecies, and that viruses likely play a predominate role in this differentiation, with SIV being a likely selective agent. Interestingly, our results suggest that SIV has elicited distinctive adaptive responses in these two chimpanzee subspecies.
Author summary Viruses are a major factor driving recent and ongoing natural selection in mammalian genomes. Studying the effects such selection has had on chimpanzee genomes can provide valuable insights into how pathogens are affecting an endangered primate species. As there are many notable examples of cross-species transmission between other primates and humans—including the HIV/AIDS pandemic—these studies can also illuminate mechanisms of adaption to pathogens of medical and economic importance. By investigating patterns of genetic differentiation amongst the four chimpanzee subspecies, we show that genetic differences among some subspecies are due to recent genetic adaptation. The genetic variants selected uniquely in eastern chimpanzees fall disproportionally within genes that differentiate the immune response to infection by simian immunodeficiency virus (SIV) in natural vs. non-natural host species. Thus, we infer that SIV has likely elicited adaptive responses in chimpanzees, building upon a growing body of work suggesting that SIV elicits ongoing selection in African primates.