Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia
Abstract Background: Plasmodium falciparumparasite populations in Ethiopia have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there wasthe paucity of data on the genomic characterization and the evolutionary adaptations of P. falciparum isolates from the central area of Ethiopia. Method: Whole-genome analysis of 25 P. falciparum isolates from central Ethiopia, specifically from West Arsi, were studied to determine theirgenetic diversity, population structures, and signatures of selection in known drug resistance alleles against global isolates from Cambodia, Thailand, DR Congo, and Malawi.Result: A total of 18,517high-quality single-nucleotide polymorphisms (SNPs) were identifiedin Ethiopian P. falciparum isolates.About 84% of the Ethiopian P. falciparum isolates hadan FWS value >0.95showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areaswith low transmission intensity. Within host diversity of Ethiopian infectionswas significantly differentfrom East African (p < 0.001) but not Southeast Asian infections (P >0.05). We observed significant population structureby PCA andpopulation differentiation between Ethiopian parasitesand East Africa (Fst~ 10%) and Southeast Asia populations (Fst ~18%), suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, we found a total of 125 genes under balancing selection that includedama1, trap, eba175, and lsa3previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the Pfcrt,Pfdhfr,Pfdhps, Pfmdr1, and PfK13 genes. However, known drug resistance-conferring mutations analysis showed that at least one SNP marker was fixed in these genes, but not in Pfdhps and PfK13.Conclusion: Plasmodium falciparumpopulation in the central region of Ethiopia wasstructurally diverged from both Southeast Asian and other East African populations. Malaria infections in Ethiopia had low within-host diversity, and parasites carryfixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.