1. Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894-6075, USA
2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA
3. Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556-016, USA
4. Division of Communicable Disease and Immunology, Walter Reed Army Institute of Research, Washington DC 20307-5100, USA

Correspondence to: Xin-zhuan Su² Correspondence and requests for materials should be addressed to X.-z.S. (e-mail: Email: xsu@niaid.nih.gov).

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 debates^{1, 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.

1. Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894-6075, USA
2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA
3. Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556-016, USA
4. Division of Communicable Disease and Immunology, Walter Reed Army Institute of Research, Washington DC 20307-5100, USA

Correspondence to: Xin-zhuan Su² Correspondence and requests for materials should be addressed to X.-z.S. (e-mail: Email: xsu@niaid.nih.gov).