Adaptive admixture at ACKR1, the Duffy blood group locus, may have shaped Plasmodium vivax prevalence in Oman.

Abstract

Malaria in humans is largely caused by two divergent species of Plasmodium parasites, P. vivax and P. falciparum, both of which have driven the spread of protective alleles in human populations. Notably, an erythrocyte-specific Duffy null allele (Fy^ES) confers resistance to P. vivax malaria and has been identified as a target of strong, recent positive selection in multiple African-admixed populations. Here, we evaluate evidence for selection via adaptive admixture in Oman, where, compared to neighboring countries, P. vivax has recently been less common. Genetic ancestry inference using whole-genome sequence data from 100 Omani individuals suggests that 15.6% (95% confidence interval [CI]: 10.8%-20.3%) of their genetic ancestry is shared with African populations. At the Duffy locus, we find a high frequency of Fy^ES and an increase in African ancestry to 76%. Comparing with blood group serology for the same individuals, we identify an additional Duffy null allele that is rare but present across multiple Arabian Peninsula (AP) populations. Finally, we estimate the selection coefficient at Fy^ES as 0.038 (95% CI: 0.027-0.051) with likely introduction at least 59 generations ago, older than estimates in other African admixed populations. Although we also observe a higher frequency of some P. falciparum-protective alleles in Oman than in other AP populations, African ancestry is not enriched, indicating a lack of evidence for adaptive admixture driven by P. falciparum selective pressure. Together, our analyses suggest that Oman's long history with East African populations resulted in early introduction and selection for Duffy null alleles and may have influenced the prevalence of P. vivax in the region.