Post-admixture selection favours Duffy negativity in the Lower Okavango Basin

The FY*BES allele in the human Duffy blood group is nearly fixed across much of sub-Saharan Africa. Individuals homozygous for this allele (Duffy-negative) were considered resistant to red blood cell invasion by the malaria parasite Plasmodium vivax, restricting its distribution across the continent. However, as recent studies have demonstrated that P. vivax can infect Duffy-negative individuals and is widespread among African populations where FY*BES predominates, long-standing assumptions about the evolutionary relationship between Duffy negativity and parasite resistance should be re-evaluated across diverse geographic, ecological and epidemiological settings. Previous research investigating the role of natural selection in increasing the frequency of the FY*BES allele has primarily centered on admixed populations with African and non-African ancestries from regions with long-documented P. vivax transmission. Here, we focus on the Khwe foragers from the lower Okavango River Basin, where the parasite has only recently been reported. Using locus-specific statistics, simulations of neutral scenarios, and local ancestry inference, we found strong evidence for post-admixture selection promoting FY*BES introgression from Bantu-speaking populations into the Khwe. If P. vivax resistance indeed drove the rise in FY*BES allele frequency, our findings suggest that the parasite has been present in the region at least 500 to 1,000 years ago.