The impact of genetic adaptation on chimpanzee subspecies differentiation

Abstract

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.

A fully integrated machine learning scan of selection in the chimpanzee genome

“…ellioti and P.t. troglodytes ( 10 , 36 ). Coupled with our results, we find evidence that selection has been a major driver for differentiation.…”

“…mRNA preprocessing with significant enrichment of signals of selection indicating that regulatory regions are significant targets in driving adaptation). Demographic models used here are based on ( 10 ) and adapted to take into account meaningful admixture events and long-term effective population size differences between subspecies; however, it is worth mentioning that the robustness of our scan is sensitive to any misspecified demography [see ( 51 ) for a discussion]. Our statistical framework used neutral and positive selection to train the random forest algorithm using different selection times and coefficients.…”

“…Briefly, the demographic model (Figure 1 ) was adapted to include all four subspecies of chimpanzee and bonobo with all meaningful admixture events, including migration and introgression. The model was additionally adapted to account for the long-term effective population sizes for each subspecies before the bottleneck at current time, as in ( 10 ), resulting in the current estimates for effective population sizes as 39 925 for P.t. troglodytes , 12 829 for P.t.…”

A genome-wide Approximate Bayesian Computation approach suggests only limited numbers of soft sweeps in humans over the last 100,000 years

“…We used summary statistics based on the widely used comparison between neutral mutations, labelled here ENVs (Evolutionary Neutral Variants), and mutations potentially targeted by selection, labelled PSV (Possibly Selected Variants), e.g., synonymous and non-synonymous comparison (Kimura 1977; Mcdonald and Kreitman 1991). Our rational was motivated by previous studies showing that positive selection causes genome-wide excesses of candidate SNPs of selection (i.e., those with extreme values for a given neutrality statistic) within or nearby genes relative to intergenic regions (e.g., coding SNPs or cis -acting eQTLs vs intergenic SNPs (Voight, et al 2006; Frazer, et al 2007; Barreiro, et al 2008; Kudaravalli, et al 2009; Jin, et al 2012; Fagny, et al 2014; Schmidt, et al 2019)). In such studies, the ENV SNP class is the neutral baseline used to control for false discoveries (similar rates of false positive are expected across SNP classes (Barreiro, et al 2008)).…”

Identification of Structural Variation in Chimpanzees Using Optical Mapping and Nanopore Sequencing

“…Recent efforts to sequence diverse great ape genomes have led to identification of signatures of natural selection using SNV data that may help to explain features unique to chimpanzee species and subspecies [5,32,45,73]. To understand if our identified SVs might impact the outcome of such studies or explain signatures of selection previously identified, we compared our map of SVs with a recent study of natural selection in multiple genomes of the four chimpanzee subspecies (Pan troglodytes verus, troglodytes, ellioti, and schweinfurthii) mapped to the human reference genome [45].…”