A genome-wide map of diversity in Plasmodium falciparum.
Genetic variation allows the malaria parasite Plasmodium falciparum to overcome chemotherapeutic agents, vaccines and vector control strategies and remain a leading cause of global morbidity and mortality. Here we describe an initial survey of genetic variation across the P. falciparum genome. We performed extensive sequencing of 16 geographically diverse parasites and identified 46,937 SNPs, demonstrating rich diversity among P. falciparum parasites (pi = 1.16 x 10(-3)) and strong correlation with gene function. We identified multiple regions with signatures of selective sweeps in drug-resistant parasites, including a previously unidentified 160-kb region with extremely low polymorphism in pyrimethamine-resistant parasites. We further characterized 54 worldwide isolates by genotyping SNPs across 20 genomic regions. These data begin to define population structure among African, Asian and American groups and illustrate the degree of linkage disequilibrium, which extends over relatively short distances in African parasites but over longer distances in Asian parasites. We provide an initial map of genetic diversity in P. falciparum and demonstrate its potential utility in identifying genes subject to recent natural selection and in understanding the population genetics of this parasite.
Volkman
Sarah K
SK
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Sabeti
Pardis C
PC
DeCaprio
David
D
Neafsey
Daniel E
DE
Schaffner
Stephen F
SF
Milner
Danny A
DA
Daily
Johanna P
JP
Sarr
Ousmane
O
Ndiaye
Daouda
D
Ndir
Omar
O
Mboup
Soulyemane
S
Duraisingh
Manoj T
MT
Lukens
Amanda
A
Derr
Alan
A
Stange-Thomann
Nicole
N
Waggoner
Skye
S
Onofrio
Robert
R
Ziaugra
Liuda
L
Mauceli
Evan
E
Gnerre
Sante
S
Jaffe
David B
DB
Zainoun
Joanne
J
Wiegand
Roger C
RC
Birren
Bruce W
BW
Hartl
Daniel L
DL
Galagan
James E
JE
Lander
Eric S
ES
Wirth
Dyann F
DF
D000349:Africa; D000818:Animals; D001208:Asia; D002489:Central America; D002874:Chromosome Mapping / Q000379:methods*; D014644:Genetic Variation; D018503:Genome, Protozoan; D005838:Genotype; D006801:Humans; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013020:South America