Adaptive admixture atACKR1(the Duffy locus) may have shapedPlasmodium vivaxprevalence 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 (FyES) 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 Omanis suggests 9.8% (95% CI: 7.3-12.2%) of their genetic ancestry is shared with east Africa. At the Duffy locus, we find a high frequency of FyES and an increase to 76% African ancestry. 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 FyES as 0.031 (95% CI: 0.029-0.034) with likely introduction at least 59 generations ago, older than estimates in other African admixed populations. Although we also observe 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.

Characterization of Blood Group Variants in an Omani Population by Comparison of Whole Genome Sequencing and Serology

“…For instance, the RHD*𝜓 indel, erythrocyte-specific null allele in the Duffy blood group, and GYP.He(P2) alleles are most common to African populations. These alleles were found in multiple Omani blood donors from this dataset and their prevalence in the population is consistent with what is known about the shared genetic ancestry of the Omanis with East African populations 19,59,60 . Overall, this study emphasizes the necessity to increase population representation in genotype databases and indicates that whole genome sequencing paired with serology is a valuable approach for doing so in transfusion practice.…”

“…The allele frequency (AF) of RHD *ψ in the Omanis is similar to the AF in African/African American population in gnomADv4.0 29 (Figure 1), with AFs of 0.0376 and 0.0389, respectively. This is higher than the gnomADv4.0 Middle Eastern population (AF=0.0022), indicating heterogeneity across the Middle East, likely due to variation in African ancestry 19 .…”

“…As previously described 19 , short read (150bp paired-end) whole genome sequencing was performed to an average coverage of 16X at the Huntsman Cancer Institute High-Throughput Genomics Shared Resource at the University of Utah. The sequence reads were aligned to GRCh38 with BWA-MEM 20 and variants were called following the GATK best practices protocol 21,22 .…”

“…A description of the samples used in this analysis, including DNA extraction and shipping conditions, has been previously published 19 . Briefly, 100 healthy male and female Omani blood donors between the ages of 18 and 60 years attending the Sultan Qaboos University Hospital (SQUH) blood bank were randomly selected and consented for enrollment in the study.…”

“…To identify copy number variation, we inferred the underlying copy number state from observed coverage at sites with high mappability in 1600bp windows across the GYPA, GYPB and GYPE loci using a Hidden Markov Model as previously described 19,25 .…”