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

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-ligan... Full description

Journal Title: Malaria Journal 2019, Vol.18
Main Author: Fu-Shi, Quan
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 14752875 ; DOI: 10.1186/s12936-019-2782-2
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title: Plasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)
format: Article
creator:
  • Fu-Shi, Quan
subjects:
  • Malaysia
  • Plasmodium Knowlesi
  • Thailand
  • Southeast Asia
  • Borneo
  • Analysis
  • Strain
  • Phylogenetics
  • Disease Control
  • Public Health
  • Antigens
  • Evolution
  • Peptides
  • Haplotypes
  • Negative Selection
  • Pressure
  • Genetic Diversity
  • Malaria
  • Proteins
  • Statistical Analysis
  • Samples
  • Proteins
  • Population Genetics
  • Studies
  • Recombination
  • Human Diseases
  • Vector-Borne Diseases
  • Recombination
  • Regions
  • Infections
  • Clinical Isolates
  • Genes
  • Software
  • Population
  • Genetic Analysis
  • Gene Polymorphism
  • Vaccines
  • Length
  • Malaria
  • Vaccines
  • Genetic Diversity
  • Genes
  • Phylogeny
  • Natural Selection
  • Genetic Diversity
  • Malaria
  • Malaria
  • Natural Selection
  • Haplotypes
  • Parasites
  • Receptors
  • Single-Nucleotide Polymorphism
  • Antigens
  • Vaccines
  • Nucleotides
  • Polymorphism
  • Genetic Diversity
  • Plasmodium Knowlesi
  • Merozoite Surface Protein 7d
  • Genetic Diversity
  • Positive Selection
  • Haplotypes
  • Malaysia
ispartof: Malaria Journal, 2019, Vol.18
description: 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 characteriz
language: eng
source:
identifier: E-ISSN: 14752875 ; DOI: 10.1186/s12936-019-2782-2
fulltext: fulltext_linktorsrc
issn:
  • 14752875
  • 1475-2875
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titlePlasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)
creatorFu-Shi, Quan
ispartofMalaria Journal, 2019, Vol.18
identifierE-ISSN: 14752875 ; DOI: 10.1186/s12936-019-2782-2
subjectMalaysia ; Plasmodium Knowlesi ; Thailand ; Southeast Asia ; Borneo ; Analysis ; Strain ; Phylogenetics ; Disease Control ; Public Health ; Antigens ; Evolution ; Peptides ; Haplotypes ; Negative Selection ; Pressure ; Genetic Diversity ; Malaria ; Proteins ; Statistical Analysis ; Samples ; Proteins ; Population Genetics ; Studies ; Recombination ; Human Diseases ; Vector-Borne Diseases ; Recombination ; Regions ; Infections ; Clinical Isolates ; Genes ; Software ; Population ; Genetic Analysis ; Gene Polymorphism ; Vaccines ; Length ; Malaria ; Vaccines ; Genetic Diversity ; Genes ; Phylogeny ; Natural Selection ; Genetic Diversity ; Malaria ; Malaria ; Natural Selection ; Haplotypes ; Parasites ; Receptors ; Single-Nucleotide Polymorphism ; Antigens ; Vaccines ; Nucleotides ; Polymorphism ; Genetic Diversity ; Plasmodium Knowlesi ; Merozoite Surface Protein 7d ; Genetic Diversity ; Positive Selection ; Haplotypes ; Malaysia
descriptionBackground 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.
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titlePlasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)
descriptionBackground 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.
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titlePlasmodium knowlesi clinical isolates from Malaysia show extensive diversity and strong differential selection pressure at the merozoite surface protein 7D (MSP7D)
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8Disease Control
9Public Health
10Antigens
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12Peptides
13Haplotypes
14Negative Selection
15Pressure
16Genetic Diversity
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abstractBackground 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.
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