Patterns of Diversity in HIV-Related Loci among Subspecies of Chimpanzee: Concordance at CCR5 and Differences at CXCR4 and CX3CR1

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Abstract
Human immunodeficiency virus type 1 (HIV-1) arose in humans via zoonotic transmissions of simian immunodeficiency viruses (SIVcpz) from common chimpanzees, Pan troglodytes. Despite the close relatedness of the two viruses and their hosts, we do not yet understand what causes SIVcpz to be nonpathogenic in chimpanzees, and HIV/AIDS to be one of the most devastating infectious diseases to have emerged in humans. There have been a number of genes identified in humans that confer disease resistance/susceptibility toward HIV-1, but little is known about the evolution and diversity of most of these chemokine receptor genes in chimpanzees. Here we show that genetic variation in chimpanzees differs across the various loci related to HIV-1, and that the pattern of variation differs among the chimpanzee subspecies. For all three subspecies, low diversity at CCR5 is confined to a small area of chromosome 3, suggesting that a selective sweep at this locus may have predated subspeciation. In contrast, diversity and neutrality tests suggest differing evolutionary forces among subspecies at CXCR4 and CX3CR1, with directional selection (in Pan troglodytes vellerosus) and demographic expansion (Pan troglodytes troglodytes) offering the most likely scenarios. These are some of the first data demonstrating differentiation in functional loci among chimpanzee subspecies.