Molecular population genetic study on the evolution of antigen polymorphism of malaria parasites

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The merozoite surface protein 1 (MSP-1) of Plasmodium falciparum is a strong malaria vaccine candidate. However, the highly polymorphic nature of the gene encoding MSP-1 (mspl) presents a potential obstacle to the development of effective vaccines. Also, there is a growing concern of the potential emergence of vaccine resistance because antigen polymorphism is believed to evolve rapidly as seen in resistance to anti-malarial drugs. To assess how rapidly parasites are able to generate novel mspl diversity, investigations of the evolutionary history of mspl polymorphism in modern parasite populations are crucial. Our previous analyses of P falciparum populations from Vanuatu in the southwestern Pacific have shown that single nucleotide polymorphisms (SNPs) in major surface antigen genes, including mspl do not evolve rapidly, whereas repeat length polymorphisms do evolve rapidly. To infer the age of SNPs of mspl in the world parasite populations, we obtained and compared more than 300 complete sequences from geographically diverse areas ; Tanzania, Thailand, Solomon Islands and Brazil. A Tanzanian parasite population showed higher nucleotide diversity than other populations, and a large number of identical SNPs, including synonymous SNPs, were shared between Tanzania and other areas. In contrast to mspl, serca, a selectively neutral gene encoding a P-type calcium-transporting ATPase (PfATP6), had limited numbers of SNPs, as expected, and nucleotide diversity was lower in serca than in mspl in all the geographic areas. Importantly, sharing of identical SNPs was substantially limited in serca between Tanzania and other areas. Together with data of the time to the most recent common ancestor (TMRCA) of parasite populations in geographic areas, our results indicate that much of SNPs in mspl are stable for a considerably long term with the age predating the recent expansion of modern humans out-of-Africa.