Genetic polymorphism and natural selection in the C-terminal 42 kDa region of merozoite surface protein-1 (MSP-1) among Plasmodium knowlesi samples from Malaysia

Abstract

BackgroundThe merozoite surface protein-1 (MSP-1) gene encodes for a leading malaria vaccine candidate antigen. However, its extensive polymorphic nature represents a major obstacle to the development of a protective vaccine. Previously, a pilot study was carried out to explore the sequence variation of the C-terminal 42 kDa fragment within P. knowlesi MSP-1 gene (PkMSP-142) based on 12 clinical samples; however, further study on an adequate sample size is vital in estimating the genetic diversity of the parasite population.MethodsIn the present study, we included a larger sample size of P. knowlesi (83 samples) covering eight states of Malaysia to determine the genetic polymorphism, natural selection and haplotype groups of the gene fragment coding PkMSP-142. The region flanking PkMSP-142 was amplified by PCR and directly sequenced. Genetic diversity, haplotype diversity, population genetic differentiation and natural selection were determined in order to study the polymorphic characteristic of PkMSP-142.ResultsA high level of genetic diversity (Hd = 0.970 ± 0.007; л = 0.01079 ± 0.00033) was observed among the 83 P. knowlesi samples, confirming the extensive genetic polymorphism exhibited among the P. knowlesi population found in Malaysia. A total of 18 distinct haplotypes with 17 amino acid changes were identified, whereby 15 were new haplotypes. High population differentiation values were observed within samples from Peninsular Malaysia and Malaysian Borneo. The 42 kDa fragments of P. knowlesi from Malaysian Borneo were found to be acting on balancing selection whilst purifying selection was suggested to act on isolates from Peninsular Malaysia. The separation of PkMSP-142 haplotypes into two main groups based on geographical separation has further supported the existence of two distinct P. knowlesi lineages.ConclusionsA high level of genetic diversity was observed among PkMSP-142 in Malaysia, whereby most of the polymorphisms were found within the 33 kDa region. Taken together, these data will be useful in order to understand the nature of P. knowlesi population in Malaysia as well as the design and development of a MSP-142 based knowlesi malaria vaccine.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-3234-5) contains supplementary material, which is available to authorized users.

Genetic population of Plasmodium knowlesi during pre-malaria elimination in Thailand

“…Plasmodium knowlesi samples from Thailand were used to create a dendrogram of the merozoite surface protein 1 (pkmsp1), which was compared to previous findings from Thailand [ 22 , 23 ], and Malaysia [ 25 , 26 ] was developed (Fig. 3 ).…”

“…To demonstrate the relationship between P. knowlesi parasites isolated in Thailand, Malaysia, and Cambodia, the DNA sequencing data of P. knowlesi merozoite surface protein 1 (pkmsp1 ) gene obtained in this study and previous data [ 22 , 23 , 25 , 26 ]were used to construct a phylogenetic tree, using MEGA X ( https://www.megasoftware.net/ ) based on neighbour-join (NJ) and BioNJ algorithms with branch lengths measured as the number of substitutions per site.…”

“…The present study aimed to analyse the genetic population of P. knowlesi parasites in Thailand and compare them with previous published findings of parasites isolated from Thailand [ 22 , 23 ], Cambodia [ 20 ] and Malaysia [ 24 – 26 ]. Network analyses based on microsatellite markers were performed and constructed a phylogenetic tree based on the nucleotide sequences of the P. knowlesi merozoite surface protein 1 gene ( pkmsp1 ).…”

Shared Signature of Recent Positive Selection on the TSBP1–BTNL2–HLA-DRA Genes in Five Native Populations from North Borneo

“…We found that none of the putative selection signals identified in the Orang Asli presented in the NB native populations, suggesting plausible attribution to their different population histories; presumably the adaptations occurred after the population diverged. In addition, recent reports suggested that the predisposition of Plasmodium parasites differed between NB and Peninsular Malaysia populations ( Yap et al. 2018 ; Hussin et al.…”

Association Between Ghrelin Gene Polymorphism and Cerebral Infarction

“…Gene polymorphism refers to the individual differences in alleles or genotypes at the same locus in the population, which increases or decreases susceptibility of the population to some diseases, or affects the gene expression, thereby affecting the occurrence of disease [ 6 , 7 ]. Studies have demonstrated that multiple gene polymorphisms affect the occurrence of cerebral infarction.…”