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NovAbstract:
Malaria is a deadly disease that causes nearly one million deaths each year. To develop methods to control and eradicate malaria, it is important to understand the genetic basis of Plasmodium falciparum adaptations to antimalarial treatments and the human immune system while taking into account its demographic history. To study the demographic history and identify genes under selection more efficiently, we sequenced the complete genomes of 25 culture-adapted P. falciparum isolates from three sites in Senegal. We show that there is no significant population structure among these Senegal sampling sites. By fitting demographic models to the synonymous allele-frequency spectrum, we also estimated a major 60-fold population expansion of this parasite population approximately 20,000-40,000 years ago. Using inferred demographic history as a null model for coalescent simulation, we identified candidate genes under selection, including genes identified before, such as pfcrt and PfAMA1, as well as new candidate genes. Interestingly, we also found selection against G/C to A/T changes that offsets the large mutational bias toward A/T, and two unusual patterns: similar synonymous and nonsynonymous allele-frequency spectra, and 18% of genes having a nonsynonymous-to-synonymous polymorphism ratio >1.
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Chang, Hsiao-HanPark, Daniel JGalinsky, Kevin JSchaffner, Stephen FNdiaye, DaoudaNdir, OmarMboup, SouleymaneWiegand, Roger CVolkman, Sarah KSabeti, Pardis CWirth, Dyann FNeafsey, Daniel EHartl, Daniel Leng(D43TW001503/TW/FIC NIH HHS/1R01AI075080-01A1/AI/NIAID NIH HHS/1R56AI082589/AI/NIAID NIH HHS/5R01GM061351/GM/NIGMS NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.2012/06/27 06:00Mol Biol Evol. 2012 Nov;29(11):3427-39. doi: 10.1093/molbev/mss161. Epub 2012 Jun 24.