Comparative genomic analysis of Plasmodium falciparumisolates from Ethiopian West Arsi, East Africa and Southeast Asia

Abstract

Local selective pressures from host immunityand drugs have led the Plasmodium falciparum (P. falciparum) parasite population to evolutionary adaptation. However, the evolutionary adaptations and genomic characteristics of P. falciparum isolates from the west Arsi, Ethiopia are poorly understood. After removing 9 samples with low quality SNPs, 25 P. falciparum isolates fromEthiopianwest Arsiwere studied to determine their population structures, genetic diversity, and signatures of selection in known drug resistance genesagainst isolates from Cambodia, DR Congo, Malawi and Thailand.About 18,517 high-quality single-nucleotide polymorphisms (SNPs) were identified in P. falciparum isolates from West Arsi, Ethiopia with overall average nucleotide diversity (π = 0.00022) across the genome. Most of the P. falciparum isolates (84%) from west Arsi of Ethiopia showed FWS value >0.95 indicating single genotype infection dominance in most samples at the time of sample collection as expected in parasites in low area of transmissions. The Ethiopian P. falciparum population ofwest Arsiwas structurally differentiated from Southeast Asian and east African populations, suggesting independent evolution of the EthiopianWest Arsi parasite population. Furthermore, a total of 125 genes known to be under balancing selection were identified. These genesincludedama1, trap, eba175, and lsa3, which were previously identified as human host immune targets and responsible for vaccine development. The directional selection signature analysis with integrated standardized haplotype score (IHS) did not detect any recent selection signatures in the Pfdhps,Pfmdr1,Pfdhfr, Pfcrt, and PfK13 genesof P. falciparum isolates from west Arsi, Ethiopia. However, known antimalarial resistance-conferring SNPs analysis detected at least one SNP marker that was fixed in these genes, but not in PfK13andPfdhps.The EthiopianP. falciparum of West Arsiwas structurally diverged from both other East African and Southeast AsianP. falciparum populations. The EthiopianP. falciparum population of West Arsicarries fixed chloroquine and Sulfadoxine/Pyrimethamine (SP) resistance markers despite the removal of these drugs from the NationalP. falciparum malaria treatment program of Ethiopia.