title: Evolution of the Transmission-Blocking Vaccine Candidates Pvs28 and Pvs25 in Plasmodium vivax: Geographic Differentiation and Evidence of Positive Selection.
abstract: Transmission-blocking (TB) vaccines are considered an important tool for malaria control and elimination. Among all the antigens characterized as TB vaccines against Plasmodium vivax, the ookinete surface proteins Pvs28 and Pvs25 are leading candidates. These proteins likely originated by a gene duplication event that took place before the radiation of the known Plasmodium species to primates. We report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. Our results show that both genes display low levels of genetic polymorphism when compared to the merozoite surface antigens AMA-1 and MSP-1; however, both ookinete antigens can be as polymorphic as other merozoite antigens such as MSP-8 and MSP-10. We found that parasite populations in Asia and the Americas are geographically differentiated with comparable levels of genetic diversity and specific amino acid replacements found only in the Americas. Furthermore, the observed variation was mainly accumulated in the EGF2- and EGF3-like domains for P. vivax in both proteins. This pattern was shared by other closely related non-human primate parasites such as Plasmodium cynomolgi, suggesting that it could be functionally important. In addition, examination with a suite of evolutionary genetic analyses indicated that the observed patterns are consistent with positive natural selection acting on Pvs28 and Pvs25 polymorphisms. The geographic pattern of genetic differentiation and the evidence for positive selection strongly suggest that the functional consequences of the observed polymorphism should be evaluated during development of TBVs that include Pvs25 and Pvs28.
authors.affiliation: Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Chaurio
authors.affiliation: Institute for Genomics and Evolutionary Medicine (iGEM), Temple University, Philadelphia, Pennsylvania, United States of America.|Department of Biology, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: M Andreína
authors.initials: MA
authors.lastname: Pacheco
authors.affiliation: School of Biological Sciences, Washington State University, Pullman, Washington, United States of America.
authors.forename: Omar E
authors.initials: OE
authors.lastname: Cornejo
authors.affiliation: Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
authors.forename: Ester
authors.initials: E
authors.lastname: Durrego
authors.affiliation: Institute for Genomics and Evolutionary Medicine (iGEM), Temple University, Philadelphia, Pennsylvania, United States of America.|Department of Biology, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Stanley
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Andreína I
authors.initials: AI
authors.lastname: Castillo
authors.affiliation: Centro de Investigación Científica Caucaseco, Cali, Colombia.
authors.forename: Sócrates
authors.initials: S
authors.lastname: Herrera
authors.affiliation: Institute for Genomics and Evolutionary Medicine (iGEM), Temple University, Philadelphia, Pennsylvania, United States of America.|Department of Biology, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ananias A
authors.initials: AA
authors.lastname: Escalante
mesh_terms: D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006239:Haplotypes; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016780:Malaria, Vivax / Q000469:parasitology / Q000517:prevention & control* / Q000635:transmission*; D008958:Models, Molecular; D010966:Plasmodium vivax / Q000235:genetics*; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D012641:Selection, Genetic
chemical_list: D017780:Malaria Vaccines; D015800:Protozoan Proteins