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Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum

机译：恶性疟原虫的遗传多样性和氯喹选择性扫描

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摘要

Widespread use of antimalarial agents can profoundly influence the evolution of the human malaria parasite Plasmodium falciparum. Recent selective sweeps for drug-resistant genotypes may have restricted the genetic diversity of this parasite, resembling effects attributed in current debates to a historic population bottleneck. Chloroquine-resistant (CQR) parasites were initially reported about 45 years ago from two foci in southeast Asia and South America, but the number of CQR founder mutations and the impact of chlorquine on parasite genomes worldwide have been difficult to evaluate. Using 342 highly polymorphic micro-satellite markers from a genetic map, here we show that the level of genetic diversity varies substantially among different regions of the parasite genome, revealing extensive linkage disequilibrium surrounding the key CQR gene pfcrt and at least four CQR founder events. This disequilibrium and its decay rate in the pfcrt-flanking region are consistent with strong directional selective sweeps occurring over only ～ 20-80 sexual generations, especially a single resistant pfcrt haplotype spreading to very high frequencies throughout most of Asia and Africa. The presence of linkage disequilibrium provides a basis for mapping genes under drug selection in P. falciparum.
机译：抗疟药的广泛使用可以深刻影响人类疟疾寄生虫恶性疟原虫的进化。最近对耐药基因型的选择性扫描可能已经限制了该寄生虫的遗传多样性，类似于当前辩论中归因于历史人口瓶颈的影响。大约在45年前，东南亚和南美的两个疫源地首次报告了耐氯喹（CQR）的寄生虫，但是很难评估CQR创始人突变的数量和氯喹对全世界寄生虫基因组的影响。使用来自遗传图谱的342个高度多态性微卫星标记，我们在这里显示了寄生虫基因组不同区域之间的遗传多样性水平存在很大差异，揭示了关键CQR基因pfcrt周围的广泛连锁不平衡和至少四个CQR创始人事件。这种在pfcrt侧翼区域的不平衡及其衰减率与仅在约20至80个性世代中发生的强方向选择性扫描相符，尤其是在亚洲和非洲大部分地区传播到很高频率的单一抗性pfcrt单倍型。连锁不平衡的存在为恶性疟原虫药物选择下的基因定位提供了基础。

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