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Background  The 200 kDa merozoite surface protein 1 (MSP-1) of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response.  Plasmodium vivax , the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to  P. vivax -related malaria parasites greatly differ among host species (albeit other factors). It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity.    Results  We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 ( msp1 ) from  P. vivax  and nine  P. vivax -related simian malaria parasites. The inferred phylogenetic tree of  msp1  significantly differed from that of the mitochondrial genome, with a striking displacement of  P. vivax  from a position close to  P. cynomolgi  in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to  P. inui  and  P. hylobati  and the other leading to  P. vivax ,  P. fieldi  and  P. cynomolgi . This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of  msp1  polymorphisms between  P. vivax ,  P. inui  and  P. cynomolgi  revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species-specifically on  msp1 .    Conclusions  The present results indicate that the  msp1  locus of  P. vivax  and related parasite species has lineage-specific unique evolutionary history with positive selection.  P. vivax  and related simian malaria parasites offer an interesting system toward understanding host species-dependent adaptive evolution of immune-target surface antigen genes such as  msp1 .

Lineage-specific positive selection at the merozoite surface protein 1 (msp1) locus of Plasmodium vivax and related simian malaria parasites