Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum

John C. Wootton, Xiaorong Feng, Michael T. Ferdig, Roland A. Cooper, Jianbing Mu, Dror I. Baruch, Alan J. Magill and Xin-zhuan Su ()
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John C. Wootton: National Institutes of Health
Xiaorong Feng: National Institutes of Health
Michael T. Ferdig: University of Notre Dame
Roland A. Cooper: National Institutes of Health
Jianbing Mu: National Institutes of Health
Dror I. Baruch: National Institutes of Health
Alan J. Magill: National Institutes of Health
Xin-zhuan Su: National Institutes of Health

Nature, 2002, vol. 418, issue 6895, 320-323

Abstract: Abstract 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 debates1,2,3,4 to a historic population bottleneck. Chloroquine-resistant (CQR) parasites were initially reported about 45 years ago from two foci in southeast Asia and South America5, 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 microsatellite markers from a genetic map6, 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 pfcrt7 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.

Date: 2002
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DOI: 10.1038/nature00813

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