title: The origin and diversification of the merozoite surface protein 3 (msp3) multi-gene family in Plasmodium vivax and related parasites.
abstract: The genus Plasmodium is a diversified group of parasites with more than 200 known species that includes those causing malaria in humans. These parasites use numerous proteins in a complex process that allows them to invade the red blood cells of their vertebrate hosts. Many of those proteins are part of multi-gene families; one of which is the merozoite surface protein-3 (msp3) family. The msp3 multi-gene family is considered important in the two main human parasites, Plasmodium vivax and Plasmodium falciparum, as its paralogs are simultaneously expressed in the blood stage (merozoite) and are immunogenic. There are large differences among Plasmodium species in the number of paralogs in this family. Such differences have been previously explained, in part, as adaptations that allow the different Plasmodium species to invade their hosts. To investigate this, we characterized the array containing msp3 genes among several Plasmodium species, including P. falciparum and P. vivax. We first found no evidence indicating that the msp3 family of P. falciparum was homologous to that of P. vivax. Subsequently, by focusing on the diverse clade of nonhuman primate parasites to which P. vivax is closely related, where homology was evident, we found no evidence indicating that the interspecies variation in the number of paralogs was an adaptation related to changes in host range or host switches. Overall, we hypothesize that the evolution of the msp3 family in P. vivax is consistent with a model of multi-allelic diversifying selection where the paralogs may have functionally redundant roles in terms of increasing antigenic diversity. Thus, we suggest that the expressed MSP3 proteins could serve as "decoys", via antigenic diversity, during the critical process of invading the host red blood cells.
authors.affiliation: Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ, USA. Electronic address: Benjamin.Rice@asu.edu.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Rice
authors.affiliation: Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ, USA. Electronic address: mmacost1@asu.edu.
authors.forename: Mónica M
authors.initials: MM
authors.lastname: Acosta
authors.affiliation: Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ, USA. Electronic address: Maria.Pacheco@asu.edu.
authors.forename: M Andreína
authors.initials: MA
authors.lastname: Pacheco
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA. Electronic address: Jane.Carlton@nyu.edu.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Carlton
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: wzb3@cdc.gov.
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
authors.affiliation: Center for Evolutionary Medicine and Informatics, The Biodesign Institute, Arizona State University, Tempe, AZ, USA; School of Life Sciences, Arizona State University, Tempe, AZ, USA. Electronic address: Ananias.Escalante@asu.edu.
authors.forename: Ananias A
authors.initials: AA
authors.lastname: Escalante
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000145:classification / Q000235:genetics*; D016054:DNA, Protozoan / Q000737:chemistry; D014644:Genetic Variation; D005810:Multigene Family; D010802:Phylogeny; D010961:Plasmodium / Q000145:classification / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics; D010966:Plasmodium vivax / Q000235:genetics*; D015800:Protozoan Proteins / Q000145:classification / Q000235:genetics*; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C089133:merozoite surface protein 3, Plasmodium
keywords: Homology; Merozoite surface protein 3; Multi-gene family; Plasmodium; Plasmodium falciparum; Plasmodium vivax