Adaptive differentiation of Plasmodium falciparum populations inferred from single-nucleotide polymorphisms (SNPs) conferring drug resistance and from neutral SNPs.
BACKGROUND
Theoretical and experimental data support the geographic differentiation strategy as a valuable tool for detecting loci under selection. In the context of Plasmodium falciparum malaria, few populations have been studied, with limited genomic coverage.


METHODS
We examined geographic differentiation in P. falciparum populations on the basis of 12 single-nucleotide polymorphisms (SNPs) in 4 genes encoding drug resistance determinants, 5 SNPs in 2 genes encoding antigens, and a set of 17 putatively neutral SNPs dispersed on 13 chromosomes. We sampled 326 parasite isolates representing 7 P. falciparum populations from regions with varied levels of malaria transmission (Gabon, Kenya, Madagascar, Mali, Mayotte, Haiti, and the Philippines).


RESULTS
Frequencies of drug resistance alleles varied considerably among populations (mean F(ST), 0.52). In contrast, allele frequencies varied significantly less for antigenic and neutral SNPs (mean F(ST), 0.16 and 0.24, respectively). This contrasting pattern was more pronounced when only the African populations were considered. Signature of selection was detected for most of the resistant SNPs but not for the antigenic SNPs.


CONCLUSIONS
These data further validate the utility of geographic differentiation for identifying loci under strong positive selection, such as drug resistance loci. This study also provides frequencies of molecular makers of resistance in some overlooked populations.
Maïga-Ascofaré
Oumou
O
Unité Mixte de Recherche 216, Institut de Recherche pour le Développement, Mère et Enfant Face aux Infections Tropicales, Université Paris Descartes, Paris, France.
Le Bras
Jacques
J
Mazmouz
Rabia
R
Renard
Emmanuelle
E
Falcão
Sarah
S
Broussier
Emeline
E
Bustos
Dorina
D
Randrianarivelojosia
Milijaona
M
Omar
Sabah A
SA
Aubouy
Agnès
A
Lepère
Jean-François
JF
Jean-François
Vély
V
Djimdé
Abdoulaye A
AA
Clain
Jérôme
J
D000220:Adaptation, Biological; D000293:Adolescent; D000328:Adult; D000349:Africa; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D017125:Genes, Protozoan; D005843:Geography; D006205:Haiti; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D010679:Philippines; D010963:Plasmodium falciparum / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D016054:DNA, Protozoan