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Mol Biol Evol DOI:10.1093/molbev/mss161

Genomic sequencing of Plasmodium falciparum malaria parasites from Senegal reveals the demographic history of the population.

Publication TypeJournal Article
Year of Publication2012
AuthorsChang, H-H, Park, DJ, Galinsky, KJ, Schaffner, SF, Ndiaye, D, Ndir, O, Mboup, S, Wiegand, RC, Volkman, SK, Sabeti, PC, Wirth, DF, Neafsey, DE, Hartl, DL
JournalMol Biol Evol
Date Published2012 Nov
KeywordsAnimals, Base Composition, Demography, Gene Frequency, Genes, Protozoan, Genetics, Population, Genome, Protozoan, Humans, Linkage Disequilibrium, Malaria, Falciparum, Models, Genetic, Nucleotides, Parasites, Plasmodium falciparum, Polymorphism, Genetic, Selection, Genetic, Senegal, Sequence Analysis, DNA

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 ∼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.


Alternate JournalMol. Biol. Evol.
PubMed ID22734050
PubMed Central IDPMC3472501
Grant ListR56 AI082589 / AI / NIAID NIH HHS / United States
1R01AI075080-01A1 / AI / NIAID NIH HHS / United States
R01 GM061351 / GM / NIGMS NIH HHS / United States
5R01GM061351 / GM / NIGMS NIH HHS / United States
(D43TW001503 / TW / FIC NIH HHS / United States
1R56AI082589 / AI / NIAID NIH HHS / United States
R01 AI075080 / AI / NIAID NIH HHS / United States
D43 TW001503 / TW / FIC NIH HHS / United States