Natural selection among Eurasians at genomic regions associated with HIV-1 control

BACKGROUND: HIV susceptibility and pathogenicity exhibit both interindividual and intergroup variability. The etiology of intergroup variability is still poorly understood, and could be partly linked to genetic differences among racial/ethnic groups. These genetic differences may be traceable to different regimes of natural selection in the 60,000 years since the human radiation out of Africa. Here, we examine population differentiation and haplotype patterns at several loci identified through genome-wide association studies on HIV-1 control, as determined by viral-load setpoint, in European and African-American populations. We use genome-wide data from the Human Genome Diversity Project, consisting of 53 world-wide populations, to compare measures of F(ST )and relative extended haplotype homozygosity (REHH) at these candidate loci to the rest of the respective chromosome. RESULTS: We find that the Europe-Middle East and Europe-South Asia pairwise F(ST )in the most strongly associated region are elevated compared to most pairwise comparisons with the sub-Saharan African group, which exhibit very low F(ST). We also find genetic signatures of recent positive selection (higher REHH) at these associated regions among all groups except for sub-Saharan Africans and Native Americans. This pattern is consistent with one in which genetic differentiation, possibly due to diversifying/positive selection, occurred at these loci among Eurasians. CONCLUSIONS: These findings are concordant with those from earlier studies suggesting recent evolutionary change at immunity-related genomic regions among Europeans, and shed light on the potential genetic and evolutionary origin of population differences in HIV-1 control.