Within-population genetic diversity and population structure of Plasmodium knowlesi merozoite surface protein 1 gene from geographically distinct regions of Malaysia and Thailand

Ahmed, Atique; Chu, Ki‐Back; Vythilingam, Indra; Quan, Fu‐Shi

doi:10.1186/s12936-018-2583-z

Cited by 10 publications

(16 citation statements)

References 46 publications

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“…Shared haplotypes between parasite populations from Kapit, Betong and Sarikei (H_4) (Fig 4) indicating a common origin of parasites from the region. Similar findings with clinical isolates from Malaysian Borneo have been reported earlier with other merozoite surface proteins [26,28]. The 24 pkmsp4 nucleotide haplotypes identified in this study are listed in S2 Table.…”

Section: Resultssupporting

confidence: 89%

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Diversity pattern of Plasmodium knowlesi merozoite surface protein 4 (MSP4) in natural population of Malaysia

2019

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Human infections due to the monkey malaria parasite Plasmodium knowlesi are increasingly being reported from Malaysia. The parasite causes high parasitaemia, severe and fatal malaria in humans thus there is a need for urgent measures for its control. The MSP4 is a potential vaccine candidate, which is well studied in Plasmodium falciparum and Plasmodium vivax; however, no study has been conducted in the orthologous gene of P. knowlesi. In this study, we investigated the level of polymorphisms, haplotypes, natural selection and population structure of full-length pkmsp4 in 32 clinical samples from Malaysian Borneo along with 4 lab-adapted strains. We found low levels of polymorphism across the gene with exon I showing higher diversity than the exon II. The C- terminal epidermal growth factor (EGF) domains and GPI-anchored region within exon II were mostly conserved with only 2 non-synonymous substitutions. Although 21 amino acid haplotypes were found, the frequency of mutation at the majority of the polymorphic positions was low. We found evidence of negative selection at the exon II of the gene indicating existence of functional constraints. Phylogenetic haplotype network analysis identified shared haplotypes and indicated geographical clustering of samples originating from Peninsular Malaysia and Malaysian Borneo. High population differentiation values were observed within parasite populations originating from Malaysian Borneo (Kapit, Sarikei and Betong) and laboratory-adapted strains obtained from Peninsular Malaysia and Philippines indicating distinct population structure. This is the first study to genetically characterize the full-length msp4 gene from clinical isolates of P. knowlesi from Malaysia and thus would be very useful for future rational vaccine studies. Further studies with higher number of samples and functional characterization of the protein will be necessary.

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Section: Resultssupporting

confidence: 89%

“…High genetic diversity has been observed in clinical isolates of P . knowlesi in several ortholog vaccine antigens (like NBPXA, MSP1 and MSP7D)[11,26–28]. However, no genetic study has been done in the pkmsp4 gene from clinical isolates of Malaysia.…”

Section: Introductionmentioning

confidence: 99%

Diversity pattern of Plasmodium knowlesi merozoite surface protein 4 (MSP4) in natural population of Malaysia

2019

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“…2) and these 2 haplotype clusters may represent the two distinct clusters observed from Malaysian Borneo. Similar findings with clinical isolates from Malaysian Borneo have been reported earlier with merozoite surface proteins [17,20,26,30]. It is interesting to note that MSP8 gene has very low levels of polymorphism compared to its orthologs in P. vivax and P. falciparum [23] and thus might be an ideal candidate for vaccine design against P. knowlesi.…”

supporting

confidence: 84%

“…Low levels of polymorphism were observed across the full-length pkmsp8 gene and the majority of the SNPs were synonymous substitutions. Similar reports of high number of synonymous substitutions in msp1p and msp1 genes were observed in P. knowlesi clinical isolates with negative/purifying natural selection [20,26]. The diversity towards the non-EGF and the double EGF domains were of similar levels (π= 0.00010-0.00016), however, the number of SNPs towards the non-EGF domains was higher than EGF domain (Table 1) indicating the EGF domains were conserved.…”

supporting

confidence: 75%

“…However, high antigenic variations within parasite populations are considered as one of the major hurdles in developing an efficacious and strain-transcending vaccine. Extensive genetic diversity has been observed in clinical isolates of P. knowlesi both in the genetic level as well as in the genomic level and several known ortholog vaccine antigens have shown similar levels of high diversity [10,11,17–20]. These studies highlight the complexities involved in P. knowlesi vaccine design thus a rational approach would be necessary.…”

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Low Levels of Polymorphisms and Negative Selection in Plasmodum knowlesi Merozoite Surface Protein 8 in Malaysian Isolates

2019

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Human infections due to the monkey malaria parasite Plasmodium knowlesi is increasingly being reported from most Southeast Asian countries specifically Malaysia. The parasite causes severe and fatal malaria thus there is a need for urgent measures for its control. In this study, the level of polymorphisms, haplotypes and natural selection of full-length pkmsp8 in 37 clinical samples from Malaysian Borneo along with 6 lab-adapted strains were investigated. Low levels of polymorphism were observed across the full-length gene, the double epidermal growth factor (EGF) domains were mostly conserved, and non-synonymous substitutions were absent. Evidence of strong negative selection pressure in the non-EGF regions were found indicating functional constrains acting at different domains. Phylogenetic haplotype network analysis identified shared haplotypes and indicated geographical clustering of samples originating from Peninsular Malaysia and Malaysian Borneo. This is the first study to genetically characterize the full-length msp8 gene from clinical isolates of P. knowlesi from Malaysia; however, further functional characterization would be useful for future rational vaccine design.

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Genetic polymorphism and clustering of the Plasmodium cynomolgi Duffy binding protein 1 region II of recent macaque isolates from Peninsular Malaysia

Latif,

Noordin,

Shahari

et al. 2024

Parasitol Res

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Within-population genetic diversity and population structure of Plasmodium knowlesi merozoite surface protein 1 gene from geographically distinct regions of Malaysia and Thailand

Cited by 10 publications

References 46 publications

Diversity pattern of Plasmodium knowlesi merozoite surface protein 4 (MSP4) in natural population of Malaysia

Diversity pattern of Plasmodium knowlesi merozoite surface protein 4 (MSP4) in natural population of Malaysia

Low Levels of Polymorphisms and Negative Selection in Plasmodum knowlesi Merozoite Surface Protein 8 in Malaysian Isolates

Genetic polymorphism and clustering of the Plasmodium cynomolgi Duffy binding protein 1 region II of recent macaque isolates from Peninsular Malaysia

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