title: Lineage-specific positive selection at the merozoite surface protein 1 (msp1) locus of Plasmodium vivax and related simian malaria parasites.
abstract: 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.
authors.affiliation: Laboratory of Malariology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sawai
authors.forename: Hiroto
authors.initials: H
authors.lastname: Otani
authors.forename: Nobuko
authors.initials: N
authors.lastname: Arisue
authors.forename: Nirianne
authors.initials: N
authors.lastname: Palacpac
authors.forename: Leonardo
authors.initials: L
authors.lastname: de Oliveira Martins
authors.forename: Sisira
authors.initials: S
authors.lastname: Pathirana
authors.forename: Shiroma
authors.initials: S
authors.lastname: Handunnetti
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawai
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kishino
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Horii
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000818:Animals; D001483:Base Sequence; D054629:Genome, Mitochondrial; D000882:Haplorhini; D006790:Host-Parasite Interactions; D006801:Humans; D008288:Malaria / Q000469:parasitology* / Q000662:veterinary*; D020066:Merozoite Surface Protein 1 / Q000235:genetics* / Q000276:immunology; D010961:Plasmodium / Q000235:genetics* / Q000276:immunology; D010966:Plasmodium vivax / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D016415:Sequence Alignment
chemical_list: D020066:Merozoite Surface Protein 1