Genomic variation in Plasmodium vivax malaria reveals regions under selective pressure.
Genomic variation in Plasmodium vivax malaria reveals regions under selective pressure.
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DOI：
10.1371/journal.pone.0177134
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Clark TG
中科院分区：
文献类型：
--
作者：
Diez Benavente E;Ward Z;Chan W;Mohareb FR;Sutherland CJ;Roper C;Campino S;Clark TG
虽然间日疟原虫导致了非洲以外几乎一半的疟疾病例，但与更致命的恶性疟原虫相比，它相对被忽视。已知间日疟原虫种群具有高度的遗传多样性，由于不同的媒介物种、宿主遗传学和环境因素，可能存在地理上的差异。我们分析了跨越4大洲10个国家的46株间日疟原虫分离株的高质量基因组数据。使用群体遗传学方法，我们确定了热点的选择压力，包括以前报道的MRP1和DHPS基因，这两个假定的耐药位点。另外还发现了另一种耐药候选基因MDR1启动子区的额外拷贝和缺失，以及可能参与红细胞侵袭的Duffy结合蛋白基因（PvDBP）的重复。对于监测应用，大陆的信息标记被发现在假定的耐药基因座，我们表明，细胞器多态性可以分类间日疟原虫种群跨越大陆和区分疟原虫属。这项研究表明，间日疟原虫种群内和种群间的基因组多样性可用于阐明潜在的耐药性和入侵机制，并促进寄生虫的分子条形码用于监测应用。
Although Plasmodium vivax contributes to almost half of all malaria cases outside Africa, it has been relatively neglected compared to the more deadly P. falciparum. It is known that P. vivax populations possess high genetic diversity, differing geographically potentially due to different vector species, host genetics and environmental factors. We analysed the high-quality genomic data for 46 P. vivax isolates spanning 10 countries across 4 continents. Using population genetic methods we identified hotspots of selection pressure, including the previously reported MRP1 and DHPS genes, both putative drug resistance loci. Extra copies and deletions in the promoter region of another drug resistance candidate, MDR1 gene, and duplications in the Duffy binding protein gene (PvDBP) potentially involved in erythrocyte invasion, were also identified. For surveillance applications, continental-informative markers were found in putative drug resistance loci, and we show that organellar polymorphisms could classify P. vivax populations across continents and differentiate between Plasmodia spp. This study has shown that genomic diversity that lies within and between P. vivax populations can be used to elucidate potential drug resistance and invasion mechanisms, as well as facilitate the molecular barcoding of the parasite for surveillance applications.