Towards a Deep Understanding of the Evolutionary Forces Shaping the Genome of Chimpanzees

Despite our close evolutionary relationship and our deep curiosity for the common chimpanzee we are only starting to understand the rich genetic diversity within this species. Recent advantages in utilizing genetic markers have revealed that Pan troglodytes can be divided into two major geographically and genetically distinct lineages consisting of two subspecies each: a western African group that includes P.t. verus and P.t. ellioti and a central/eastern African group including P.t. troglodytes and P.t. schweinfurthii. The natural division of the two lineages is the Sanaga River in Cameroon where the ranges of P.t. ellioti and P.t. troglodytes converge. However, we have shown that neutral evolutionary processes resulting from separation across this biogeographic barrier alone cannot explain the differentiation between P.t. ellioti and P.t. troglodytes. In order to identify genes that show signatures of selection and might explain diversification we analyzed 32 whole genome sequences from all four subspecies. High quality single nucleotide polymorphisms (SNPs) were identified and screened to detect outlier loci either by analyzing western African and central/eastern African samples or evaluating P.t. ellioti and P.t. troglodytes samples. Three different genome scan approaches were carried out and consensus between at least two of the methods was enforced to identify outlier loci. Gene ontology (GO) enrichment analysis was carried out to determine broader characteristics of genes under selection. A total of ~12 million SNPs were screened resulting in ~11,000 outlier loci unique to P.t. ellioti and P.t. troglodytes, respectively. GO enrichment analysis revealed 22 GO terms in 1,318 genes enriched in P.t. ellioti but only 6 GO terms in 428 genes enriched in P.t. troglodytes. Both subspecies showed enrichment of genes under selection related to metabolic functions as well as genes involved in nervous system development, behavior, and regulation of biological processes. In addition enriched GO terms uniquely found in P.t. ellioti are related to genes playing a role in learning and brain development but also cell adhesion, tissue migration, and localization. We present the first extensive set of candidate genes under selection that will help to understand the diversification of two chimpanzee subspecies despite ongoing gene flow. Together with a set of neutral markers this information will be used to screen ~300 genomes from wild and geo-referenced chimpanzees to further understand their diversity and the processes leading to and maintaining it.