Open Access Research article

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

Hiromi Sawai1, Hiroto Otani1, Nobuko Arisue2, Nirianne Palacpac2, Leonardo de Oliveira Martins3, Sisira Pathirana4, Shiroma Handunnetti45, Satoru Kawai6, Hirohisa Kishino7, Toshihiro Horii2 and Kazuyuki Tanabe1*

Author Affiliations

1 Laboratory of Malariology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan

2 Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan

3 Bioinformatics and Molecular Evolution, University of Vigo, Vigo 36310, Spain

4 Malaria Research Unit, Department of Parasitology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka

5 Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka

6 Center for Tropical Medicine and Parasitology, Dokkyo Medical University, Tochigi 321-0293, Japan

7 Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan

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BMC Evolutionary Biology 2010, 10:52  doi:10.1186/1471-2148-10-52

Published: 19 February 2010



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.


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.


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.