Populations of Plasmodium falciparum, the most virulent human
malaria parasite, are diverse owing to wide levels of transmission and endemicity of
infection. Genetic diversity of P. falciparum
antigens, within and between parasite populations, remains a confounding factor in
malaria pathogenesis as well as clinical trials of
vaccine candidates. Variation of target
antigens in parasite populations may arise from immune pressure depending on the levels of acquired immunity. Alternatively, similar to our study in housekeeping genes [Tanabe et al. Curr Biol 2010;70:1-7], within-population genetic diversity of
vaccine candidate
antigens may also be determined by geographical distance from a postulated origin in Central sub-Saharan Africa. To address this question, we obtained full-length sequences of P. falciparum genes, apical membrane
antigen 1 (ama1) (n=459), circumsporozoite
protein (csp) (n=472) and
merozoite surface protein 1 (
msp1) (n=389) from seven geographically diverse parasite populations in Africa, Southeast Asia and Oceania; and, together with previously determined sequences (n=13 and 15 for csp and
msp1, respectively) analyzed within-population single nucleotide polymorphism (SNP) diversity. The three
antigen genes showed SNP diversity that supports a model of isolation-by-distance. The standardized number of polymorphic sites per site, expressed as θ(S), indicates that 77-83% can be attributed by geographic distance from the African origin, suggesting that geographic distance plays a significant role in variation in target
vaccine candidate
antigens. Furthermore, we observed that a large proportion of SNPs in the
antigen genes were shared between African and non-African parasite populations, demonstrating long term persistence of those SNPs. Our results provide important implications for developing effective
malaria vaccines and better understanding of acquired immunity against
falciparum malaria.