Abstract
Plasmodium vivax merozoite surface protein 3 (PvMSP3) is encoded by a multi-gene family. Of these, PvMSP3α, PvMSP3β and PvMSP3γ, are considered to be vaccine targets. Despite comprehensive analyses of PvMSP3α and PvMSP3β, little is known about structural and sequence diversity in PvMSP3γ. Analysis of 118 complete pvmsp3γ sequences from diverse endemic areas of Thailand and 9 reported sequences has shown 86 distinct haplotypes. Based on variation in insert domains, pvmsp3γ can be classified into 3 types, i.e. Belem, Salvador I and NR520. Imperfect nucleotide repeats were found in six regions of the gene; none encoded tandem amino acid repeats. Predicted coiled-coil heptad repeats were abundant in the protein and displayed variation in length and location. Interspersed phase shifts occurred in the heptad arrays that may have an impact on protein structure. Polymorphism in pvmsp3γ seems to be generated by intragenic recombination and driven by natural selection. Most P. vivax isolates in Thailand exhibit population structure, suggesting limited gene flow across endemic areas. Phylogenetic analysis has suggested that insert domains could have been subsequently acquired during the evolution of pvmsp3γ. Sequence and structural diversity of PvMSP3γ may complicate vaccine design due to alteration in predicted immunogenic epitopes among variants.
Highlights
Plasmodium vivax merozoite surface protein 3 (PvMSP3) is encoded by a multi-gene family
Of 150P. vivax isolates from 5 provinces, 118 pvmsp3γ complete gene sequences were obtained after exclusion of multi-clonal infections
The pvmsp3γ sequences displayed a higher level of nucleotide diversity than those observed in pvmsp3α and pvmsp3β of P. vivax populations in Thailand, i.e. 0.151, 0.033 and 0.088, respectively[10,15]
Summary
Plasmodium vivax merozoite surface protein 3 (PvMSP3) is encoded by a multi-gene family. The MSP3 proteins in P. vivax (PvMSP3) are encoded by a multi-gene family containing 12 gene members arranged in tandem[5]. Two of these members, pvmsp3α (PVX_097720) and pvmsp3β (PVX_097680), exhibit extensive sequence diversity among laboratory and field isolates[6,7,8,9,10,11,12,13]. To assess the genetic diversity and structural variation of pvmsp3γ, 118 complete coding sequences were analysed from isolates obtained from diverse endemic areas of Thailand. Results revealed spatial variation in genetic diversity while recurrent intragenic recombination and natural selection have contributed to structural and sequence diversity at this locus, an important issue for vaccine design
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