期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：50
页码：E8096-E8105
DOI：10.1073/pnas.1608828113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceIn Cambodia, where Plasmodium vivax and Plasmodium falciparum are coendemic and intense multimodal malaria-control interventions have reduced malaria incidence, P. vivax malaria has proven relatively resistant to such measures. We performed comparative genomic analyses of 150 P. vivax and P. falciparum isolates to determine whether different evolutionary strategies might underlie this species-specific resilience. Demographic modeling and tests of selection show that, in contrast to P. falciparum, P. vivax has experienced uninterrupted growth and positive selection at multiple loci encoding transcriptional regulators. In particular, a strong selective sweep involving an AP2 transcription factor suggests that P. vivax may use nuanced transcriptional approaches to population maintenance. Better understanding of P. vivax transcriptional regulation may lead to improved tools to achieve elimination. Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P. vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P. vivax and 80 P. falciparum isolates collected between 2009 and 2013. We found that although P. falciparum has undergone population fracturing, the coendemic P. vivax population has grown undisrupted, resulting in a larger effective population size, no discernable population structure, and frequent multiclonal infections. Signatures of selection suggest recent, species-specific evolutionary differences. Particularly, in contrast to P. falciparum, P. vivax transcription factors, chromatin modifiers, and histone deacetylases have undergone strong directional selection, including a particularly strong selective sweep at an AP2 transcription factor. Together, our findings point to different population-level adaptive mechanisms used by P. vivax and P. falciparum parasites. Although population substructuring in P. falciparum has resulted in clonal outgrowths of resistant parasites, P. vivax may use a nuanced transcriptional regulatory approach to population maintenance, enabling it to preserve a larger, more diverse population better suited to facing selective threats. We conclude that transcriptional control may underlie P. vivaxs resilience to malaria control measures. Novel strategies to target such processes are likely required to eradicate P. vivax and achieve malaria elimination.
