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Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence

Daniel E Neafsey1, Stephen F Schaffner1, Sarah K Volkman23, Daniel Park1, Philip Montgomery1, Danny A Milner2, Amanda Lukens2, David Rosen2, Rachel Daniels1, Nathan Houde1, Joseph F Cortese1, Erin Tyndall1, Casey Gates1, Nicole Stange-Thomann1, Ousmane Sarr4, Daouda Ndiaye4, Omar Ndir4, Soulyemane Mboup4, Marcelo U Ferreira5, Sandra do Lago Moraes6, Aditya P Dash7, Chetan E Chitnis8, Roger C Wiegand1, Daniel L Hartl9, Bruce W Birren1, Eric S Lander1, Pardis C Sabeti1 and Dyann F Wirth2*

Author Affiliations

1 Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA

2 Department of Immunology and Infectious Diseases, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA

3 School for Health Studies, Simmons College, 300 The Fenway, Boston, MA 02115, USA

4 Faculty of Medicine and Pharmacy, Cheikh Anta Diop University, BP 7325 Dakar, Senegal

5 Departamento de Parasitologia, Instituto de Ciencias Biomedicas da USP, Av. Prof. Lineu Prestes 1374, Cidade Universitaria, 05508-900 Sao Paulo, SP, Brazil

6 Instituto de Medicina Tropical de Sao Paulo, Universidade de Sao Paulo, Av Dr. Eneas de Carvalho Aguiar 470, 05403-907 Sao Paulo, SP, Brazil

7 National Institute of Malaria Research, 22, Sham Nath Marg, Delhi-110054, India

8 International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India

9 Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA

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Genome Biology 2008, 9:R171  doi:10.1186/gb-2008-9-12-r171

Published: 15 December 2008



The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum.


Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, inter-population differentiation, and the degree to which allele frequencies are correlated between populations.


The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum, and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits.