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Background  The high proportion of human cases due to the simian malaria parasite  Plasmodium knowlesi  in Malaysia is a cause of concern, as they can be severe and even fatal. Merozoite surface protein 7 (MSP7) is a multigene family which forms a non-covalent complex with MSP-1 prior to receptor-ligand recognition in  Plasmodium falciparum  and thus an important antigen for vaccine development. However, no study has been done in any of the ortholog family members in  P. knowlesi  from clinical samples. This study investigates the level of polymorphism, haplotypes, and natural selection acting at the  pkmsp - 7D  gene in clinical samples from Malaysia.    Methods  Thirty-six full-length  pkmsp7D  gene sequences (along with the reference H-strain: PKNH_1266000) obtained from clinical isolates of Malaysia, which were orthologous to  pvmsp7H  (PVX_082680) were downloaded from public databases. Population genetic, evolutionary and phylogenetic analyses were performed to determine the level of genetic diversity, polymorphism, recombination and natural selection.    Results  Analysis of 36 full-length  pkmsp7D  sequences identified 147 SNPs (91 non-synonymous and 56 synonymous substitutions). Nucleotide diversity across the full-length gene was higher than its ortholog in  Plasmodium vivax  ( msp7H ). Region-wise analysis of the gene indicated that the nucleotide diversity at the central region was very high (π = 0.14) compared to the 5′ and 3′ regions. Most hyper-variable SNPs were detected at the central domain. Multiple test for natural selection indicated the central region was under strong positive natural selection however, the 5′ and 3′ regions were under negative/purifying selection. Evidence of intragenic recombination were detected at the central region of the gene. Phylogenetic analysis using full-length  msp7D  genes indicated there was no geographical clustering of parasite population.    Conclusions  High genetic diversity with hyper-variable SNPs and strong evidence of positive natural selection at the central region of MSP7D indicated exposure of the region to host immune pressure. Negative selection at the 5′ and the 3′ regions of MSP7D might be because of functional constraints at the unexposed regions during the merozoite invasion process of  P. knowlesi . No evidence of geographical clustering among the clinical isolates from Malaysia indicated uniform selection pressure in all populations. These findings highlight the further evaluation of the regions and functional characterization of the protein as a potential blood stage vaccine candidate for  P. knowlesi .    Electronic supplementary material  The online version of this article (10.1186/s12936-019-2782-2) contains supplementary material, which is available to authorized users.

malaria journal

Plasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)