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

• Published in: Malaria Journal
• Main Authors: Md. Atique Ahmed, Fu-Shi Quan
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2019
• Subjects: Plasmodium knowlesi; Merozoite surface protein 7D; Genetic diversity; Positive selection; Haplotypes; Malaysia; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-019-2782-2; https://doaj.org/article/9a989c526000432f84b8f15db068754b

Abstract 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 ...