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Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum

Author

Listed:
  • 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
    Walter Reed Army Institute of Research)

  • Xin-zhuan Su

    (National Institutes of Health)

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.

Suggested Citation

  • John C. Wootton & Xiaorong Feng & Michael T. Ferdig & Roland A. Cooper & Jianbing Mu & Dror I. Baruch & Alan J. Magill & Xin-zhuan Su, 2002. "Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum," Nature, Nature, vol. 418(6895), pages 320-323, July.
    • Handle: RePEc:nat:nature:v:418:y:2002:i:6895:d:10.1038_nature00813
    DOI: 10.1038/nature00813
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    Cited by:

    1. Bing Guo & Victor Borda & Roland Laboulaye & Michele D. Spring & Mariusz Wojnarski & Brian A. Vesely & Joana C. Silva & Norman C. Waters & Timothy D. O’Connor & Shannon Takala-Harrison, 2024. "Strong positive selection biases identity-by-descent-based inferences of recent demography and population structure in Plasmodium falciparum," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. John D O’Brien & Zamin Iqbal & Jason Wendler & Lucas Amenga-Etego, 2016. "Inferring Strain Mixture within Clinical Plasmodium falciparum Isolates from Genomic Sequence Data," PLOS Computational Biology, Public Library of Science, vol. 12(6), pages 1-20, June.
    3. Schneider, Kristan A. & Kim, Yuseob, 2010. "An analytical model for genetic hitchhiking in the evolution of antimalarial drug resistance," Theoretical Population Biology, Elsevier, vol. 78(2), pages 93-108.

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