Genetic polymorphism and natural selection of merozoite surface protein 1 C-terminal 42 kDa in Vietnamese Plasmodium...

Plasmodium vivax merozoite surface protein-1 (PvMSP-1) is a major surface protein of merozoites and plays crucial roles in erythrocyte invasion by merozoites. PvMSP-1 undergoes sequential proteolytic cleavages during erythrocyte invasion, resulting in four fragments of 82, 30, 38, and 42 kDa. The carboxy-terminal 42 kDa fragment (PvMSP-1₄₂) is further cleaved into two smaller fragments of 33 kDa (PvMSP-1₃₃) and 19 kDa (PvMSP-1₁₉). PvMSP-1₄₂ is an attractive vaccine candidate since it induces antibody production in naturally exposed humans, and specific antibodies against this region inhibit merozoite invasion. However, the genetic polymorphisms of PvMSP-1₄₂ reported in global P. vivax isolates emphasize the importance of molecular surveillance for the vaccine candidate. In this study, we analyzed genetic polymorphism profiles and natural selection in PvMSP-1₄₂ from 88 Vietnamese P. vivax isolates collected in four malaria-endemic provinces in Vietnam. Vietnamese PvMSP-1₄₂ exhibited genetic polymorphisms resulting from nucleotide substitutions and meiotic recombination, and balancing selection might preserve the diversity of the gene. Most polymorphic sites were identified in PvMSP-1₃₃, while PvMSP-1₁₉ was relatively well-conserved. Global PvMSP-1₄₂ displayed similar, but not identical, polymorphic features and natural selection profiles. No geographical clustering was identified. Nevertheless, PvMSP-1₁₉ was well-conserved across global populations. These findings expand our understanding of the genetic structure and evolutionary dynamics of PvMSP-1₄₂, and provide valuable information for developing an effective malaria vaccine based on the protein.