Abstract:
: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.
journal_name
Mol Biol Evoljournal_title
Molecular biology and evolutionauthors
Chang HH,Park DJ,Galinsky KJ,Schaffner SF,Ndiaye D,Ndir O,Mboup S,Wiegand RC,Volkman SK,Sabeti PC,Wirth DF,Neafsey DE,Hartl DLdoi
10.1093/molbev/mss161subject
Has Abstractpub_date
2012-11-01 00:00:00pages
3427-39issue
11eissn
0737-4038issn
1537-1719pii
mss161journal_volume
29pub_type
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