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Understandingthe mechanisms of drug resistance in Plasmodium vivax, the parasite that causes the most widespread form of human malaria,is complicated by the lack of a suitable long-term cell culture systemfor this parasite. In contrast to P. falciparum,which can be more readily manipulated in the laboratory, insightsabout parasite biology need to be inferred from human studies. Herewe analyze the genomes of parasites within 10 human P. vivax infections from the Peruvian Amazon. Using next-generation sequencingwe show that some P. vivax infections analyzed fromthe region are likely polyclonal. Despite their polyclonality we observelimited parasite genetic diversity by showing that three or fewerhaplotypes comprise 94% of the examined genomes, suggesting the recentintroduction of parasites into this geographic region. In contrastwe find more than three haplotypes in putative drug-resistance genes,including the gene encoding dihydrofolate reductase-thymidylate synthaseand the P. vivax multidrug resistance associatedtransporter, suggesting that resistance mutations have arisen independently.Additionally, several drug-resistance genes are located in genomicregions with evidence of increased copy number. Our data suggest thatwhole genome sequencing of malaria parasites from patients may providemore insight about the evolution of drug resistance than genetic linkageor association studies, especially in geographical regions with limitedparasite genetic diversity.
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