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 mortality1. 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 (π = 1.16 × 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.
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We thank all members of the sample collection team in Senegal (A. Ahouidi, L. Ndiaye, O. Ly, Y. Diedhiou, T. Sene, A. Mbaye and D. Diop). We thank T. Taylor, K. Seydel, J. Montgomery, E. Dembo, M. Molyneux and S. Rogerson for help collecting the samples from Malawi. We also thank all the members of the Broad Sequencing Platform and M. Koehrsen, D. Richter and O. Shamovsky for sequence analysis help. Our thanks to M. Goyette and T. Rachupka for help with Sequenom genotyping. Thanks to N. Mahesh and G. Ramirez for help with sample preparation and parasite cultures and to J. Mu and X. Su for typing samples. We thank MR4 for providing us with malaria parasites contributed by the following depositors: W.E. Collins (MRA-347); D.E. Kyle (MRA-154, MRA-157, MRA-159, MRA-176, MRA-207, MRA-284, MRA-285); L.H. Miller and D. Baruch (MRA-331, MRA-326, MRA-328); W. Trager (MRA-731, MRA-732, MRA-733); D. Walliker (MRA-151, MRA-153, MRA-200); T.E. Wellems (MRA-155, MRA-156, MRA-309, MRA-464); and Y. Wu (MRA-201). Special thanks to J. Barnwell for providing P. reichenowi DNA. Our thanks to PlasmoDB (http://www.plasmodb.org) for access to the 3D7 genome sequence. The authors are supported by the US National Institutes of Health, SPARC funding of The Broad Institute of MIT and Harvard, the Burroughs-Wellcome Fund, The Bill and Melinda Gates Foundation, the NIAID Microbial Sequencing Center, the Ellison Medical Foundation, Fogarty International and the Exxon Mobil Foundation. P.C.S. is funded by the Damon Runyon Cancer Fellowship and the L'Oreal for Women in Science Award.
Sample correspondence for SNPs.
Separation of continental populations using genotyping SNPs.
Allele frequency in spectra.
Parasites used in the study.
Twenty chromosomal regions selected for LD study.
Nucleotide diversity across the genome.
Comparison of genotyping from whole genome–amplified samples and the original unamplified sample.