Genomic sequencing of Plasmodium falciparum malaria parasites from Senegal reveals the demographic history of the population.
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.
Department of Organismic and Evolutionary Biology, Harvard University. hhchang@oeb.harvard.edu
Hsiao-Han
HH
Chang
Daniel J
DJ
Park
Kevin J
KJ
Galinsky
Stephen F
SF
Schaffner
Daouda
D
Ndiaye
Omar
O
Ndir
Souleymane
S
Mboup
Roger C
RC
Wiegand
Sarah K
SK
Volkman
Pardis C
PC
Sabeti
Dyann F
DF
Wirth
Daniel E
DE
Neafsey
Daniel L
DL
Hartl
D000818:Animals; D001482:Base Composition / Q000235:genetics; D003710:Demography; D005787:Gene Frequency / Q000235:genetics; D017125:Genes, Protozoan / Q000235:genetics; D005828:Genetics, Population; D018503:Genome, Protozoan / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D016778:Malaria, Falciparum / Q000235:genetics / Q000469:parasitology*; D008957:Models, Genetic; D009711:Nucleotides / Q000235:genetics; D010271:Parasites / Q000235:genetics* / Q000254:growth & development; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D012675:Senegal; D017422:Sequence Analysis, DNA
D009711:Nucleotides