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The Plasmodium knowlesi Pk41 surface protein diversity, natural selection, sub population and geographical clustering: a 6-cysteine protein family member

Introduction The zoonotic malaria parasite Plasmodium knowlesi has currently become the most dominant form of infection in humans in Malaysia and is an emerging infectious disease in most Southeast Asian countries. The P41 is a merozoite surface protein belonging to the 6-cysteine family and is a we... Full description

Journal Title: PeerJ Dec 14, 2018
Main Author: Fu-Shi, Quan
Format: Electronic Article Electronic Article
Language: English
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ID: E-ISSN: 21678359 ; DOI: 10.7717/peerj.6141
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title: The Plasmodium knowlesi Pk41 surface protein diversity, natural selection, sub population and geographical clustering: a 6-cysteine protein family member
format: Article
creator:
  • Fu-Shi, Quan
subjects:
  • Malaysia
  • South Korea
  • China
  • Plasmodium Knowlesi
  • Myanmar (Burma)
  • Borneo
  • Infections
  • Laboratories
  • Clinical Isolates
  • Cysteine
  • Vaccines
  • Gene Polymorphism
  • Evolution
  • Amino Acids
  • Glutamic Acid
  • Infectious Diseases
  • Erythrocytes
  • Haplotypes
  • Genetic Diversity
  • Phylogeny
  • Proteins
  • Malaria
  • Malaria
  • Natural Selection
  • Computer Programs
  • Parasites
  • Studies
  • Subpopulations
  • Single-Nucleotide Polymorphism
  • Antigens
  • Vaccines
  • Polymorphism
  • Zoonoses
  • Genetic Diversity
  • Tropical Diseases
  • World Health Organization
  • Kyung Hee University
  • Plasmodium Knowlesi
  • Pk41
  • Natural Selection
  • 6-Cysteine Family
  • S48/45 Domain
  • Polymorphism
  • Malaysia
  • Clinical Samples
  • Low Diversity
  • Vaccine
ispartof: PeerJ, Dec 14, 2018
description: Introduction The zoonotic malaria parasite Plasmodium knowlesi has currently become the most dominant form of infection in humans in Malaysia and is an emerging infectious disease in most Southeast Asian countries. The P41 is a merozoite surface protein belonging to the 6-cysteine family and is a well-characterized vaccine candidate in P. vivax and P. falciparum; however, no study has been done in the orthologous gene of P. knowlesi. This study investigates the level of polymorphism, haplotypes and natural selection of pk41 genes in clinical isolates from Malaysia. Method Thirty-five full-length pk41 sequences from clinical isolates of Malaysia along with four laboratory lines (along with H-strain) were downloaded from public databases. For comparative analysis between species, orthologous P41 genes from P. falciparum, P. vivax, P. coatneyi and P. cynomolgi were also downloaded. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. Phylogenetic relationships between Pk41 genes were determined using MEGA 5.0 software. Results Analysis of 39 full-length pk41 sequences along with the H-strain identified 36 SNPs (20 non-synonymous and 16 synonymous substitutions) resulting in 31 haplotypes. Nucleotide diversity across the full-length gene was low and was similar to its ortholog in P. vivax; pv41. Domain-wise amino acid analysis of the two s48/45 domains indicated low level of polymorphisms for both the domains, and the glutamic acid rich region had extensive size variations. In the central domain, upstream to the glutamate rich region, a unique two to six (K-E)n repeat region was identified within the clinical isolates. Overall, the pk41 genes were indicative of negative/purifying selection due to functional constraints. Domain-wise analysis of the s48/45 domains also indicated purifying selection. However, analysis of Tajima’s D across the genes identified non-synonymous SNPs in the s48/45 domain II with high positive values indicating possible epitope binding regions. All the 6-cysteine residues within the s48/45 domains were conserved within the clinical isolates indicating functional conservation of these regions. Phylogenetic analysis of full-length pk41 genes indicated geographical clustering and identified three subpopulations of P. knowlesi; one originating in the laboratory lines and two originating from Sarawak, Malaysian Borneo. Conclusion This is the first study to report on the polymorphism and
language: eng
source:
identifier: E-ISSN: 21678359 ; DOI: 10.7717/peerj.6141
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issn:
  • 21678359
  • 2167-8359
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titleThe Plasmodium knowlesi Pk41 surface protein diversity, natural selection, sub population and geographical clustering: a 6-cysteine protein family member
creatorFu-Shi, Quan
ispartofPeerJ, Dec 14, 2018
identifierE-ISSN: 21678359 ; DOI: 10.7717/peerj.6141
subjectMalaysia ; South Korea ; China ; Plasmodium Knowlesi ; Myanmar (Burma) ; Borneo ; Infections ; Laboratories ; Clinical Isolates ; Cysteine ; Vaccines ; Gene Polymorphism ; Evolution ; Amino Acids ; Glutamic Acid ; Infectious Diseases ; Erythrocytes ; Haplotypes ; Genetic Diversity ; Phylogeny ; Proteins ; Malaria ; Malaria ; Natural Selection ; Computer Programs ; Parasites ; Studies ; Subpopulations ; Single-Nucleotide Polymorphism ; Antigens ; Vaccines ; Polymorphism ; Zoonoses ; Genetic Diversity ; Tropical Diseases ; World Health Organization ; Kyung Hee University ; Plasmodium Knowlesi ; Pk41 ; Natural Selection ; 6-Cysteine Family ; S48/45 Domain ; Polymorphism ; Malaysia ; Clinical Samples ; Low Diversity ; Vaccine
descriptionIntroduction The zoonotic malaria parasite Plasmodium knowlesi has currently become the most dominant form of infection in humans in Malaysia and is an emerging infectious disease in most Southeast Asian countries. The P41 is a merozoite surface protein belonging to the 6-cysteine family and is a well-characterized vaccine candidate in P. vivax and P. falciparum; however, no study has been done in the orthologous gene of P. knowlesi. This study investigates the level of polymorphism, haplotypes and natural selection of pk41 genes in clinical isolates from Malaysia. Method Thirty-five full-length pk41 sequences from clinical isolates of Malaysia along with four laboratory lines (along with H-strain) were downloaded from public databases. For comparative analysis between species, orthologous P41 genes from P. falciparum, P. vivax, P. coatneyi and P. cynomolgi were also downloaded. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. Phylogenetic relationships between Pk41 genes were determined using MEGA 5.0 software. Results Analysis of 39 full-length pk41 sequences along with the H-strain identified 36 SNPs (20 non-synonymous and 16 synonymous substitutions) resulting in 31 haplotypes. Nucleotide diversity across the full-length gene was low and was similar to its ortholog in P. vivax; pv41. Domain-wise amino acid analysis of the two s48/45 domains indicated low level of polymorphisms for both the domains, and the glutamic acid rich region had extensive size variations. In the central domain, upstream to the glutamate rich region, a unique two to six (K-E)n repeat region was identified within the clinical isolates. Overall, the pk41 genes were indicative of negative/purifying selection due to functional constraints. Domain-wise analysis of the s48/45 domains also indicated purifying selection. However, analysis of Tajima’s D across the genes identified non-synonymous SNPs in the s48/45 domain II with high positive values indicating possible epitope binding regions. All the 6-cysteine residues within the s48/45 domains were conserved within the clinical isolates indicating functional conservation of these regions. Phylogenetic analysis of full-length pk41 genes indicated geographical clustering and identified three subpopulations of P. knowlesi; one originating in the laboratory lines and two originating from Sarawak, Malaysian Borneo. Conclusion This is the first study to report on the polymorphism and natural selection of pk41 genes from clinical isolates of Malaysia. The results reveal that there is low level of polymorphism in both s48/45 domains, indicating that this antigen could be a potential vaccine target. However, genetic and molecular immunology studies involving higher number of samples from various parts of Malaysia would be necessary to validate this antigen’s candidacy as a vaccine target for P. knowlesi.
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titleThe Plasmodium knowlesi Pk41 surface protein diversity, natural selection, sub population and geographical clustering: a 6-cysteine protein family member
descriptionIntroduction The zoonotic malaria parasite Plasmodium knowlesi has currently become the most dominant form of infection in humans in Malaysia and is an emerging infectious disease in most Southeast Asian countries. The P41 is a merozoite surface protein belonging to the 6-cysteine family and is a well-characterized vaccine candidate in P. vivax and P. falciparum; however, no study has been done in the orthologous gene of P. knowlesi. This study investigates the level of polymorphism, haplotypes and natural selection of pk41 genes in clinical isolates from Malaysia. Method Thirty-five full-length pk41 sequences from clinical isolates of Malaysia along with four laboratory lines (along with H-strain) were downloaded from public databases. For comparative analysis between species, orthologous P41 genes from P. falciparum, P. vivax, P. coatneyi and P. cynomolgi were also downloaded. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. Phylogenetic relationships between Pk41 genes were determined using MEGA 5.0 software. Results Analysis of 39 full-length pk41 sequences along with the H-strain identified 36 SNPs (20 non-synonymous and 16 synonymous substitutions) resulting in 31 haplotypes. Nucleotide diversity across the full-length gene was low and was similar to its ortholog in P. vivax; pv41. Domain-wise amino acid analysis of the two s48/45 domains indicated low level of polymorphisms for both the domains, and the glutamic acid rich region had extensive size variations. In the central domain, upstream to the glutamate rich region, a unique two to six (K-E)n repeat region was identified within the clinical isolates. Overall, the pk41 genes were indicative of negative/purifying selection due to functional constraints. Domain-wise analysis of the s48/45 domains also indicated purifying selection. However, analysis of Tajima’s D across the genes identified non-synonymous SNPs in the s48/45 domain II with high positive values indicating possible epitope binding regions. All the 6-cysteine residues within the s48/45 domains were conserved within the clinical isolates indicating functional conservation of these regions. Phylogenetic analysis of full-length pk41 genes indicated geographical clustering and identified three subpopulations of P. knowlesi; one originating in the laboratory lines and two originating from Sarawak, Malaysian Borneo. Conclusion This is the first study to report on the polymorphism and natural selection of pk41 genes from clinical isolates of Malaysia. The results reveal that there is low level of polymorphism in both s48/45 domains, indicating that this antigen could be a potential vaccine target. However, genetic and molecular immunology studies involving higher number of samples from various parts of Malaysia would be necessary to validate this antigen’s candidacy as a vaccine target for P. knowlesi.
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1South Korea
2China
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4Myanmar (Burma)
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6Infections
7Laboratories
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10Vaccines
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13Amino Acids
14Glutamic Acid
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16Erythrocytes
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19Phylogeny
20Proteins
21Malaria
22Natural Selection
23Computer Programs
24Parasites
25Studies
26Subpopulations
27Single-Nucleotide Polymorphism
28Antigens
29Polymorphism
30Zoonoses
31Tropical Diseases
32World Health Organization
33Kyung Hee University
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356-Cysteine Family
36S48/45 Domain
37Clinical Samples
38Low Diversity
39Vaccine
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titleThe Plasmodium knowlesi Pk41 surface protein diversity, natural selection, sub population and geographical clustering: a 6-cysteine protein family member
authorFu-Shi, Quan
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7Laboratories
8Clinical Isolates
9Cysteine
10Vaccines
11Gene Polymorphism
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14Glutamic Acid
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16Erythrocytes
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18Genetic Diversity
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21Malaria
22Natural Selection
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356-Cysteine Family
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abstractIntroduction The zoonotic malaria parasite Plasmodium knowlesi has currently become the most dominant form of infection in humans in Malaysia and is an emerging infectious disease in most Southeast Asian countries. The P41 is a merozoite surface protein belonging to the 6-cysteine family and is a well-characterized vaccine candidate in P. vivax and P. falciparum; however, no study has been done in the orthologous gene of P. knowlesi. This study investigates the level of polymorphism, haplotypes and natural selection of pk41 genes in clinical isolates from Malaysia. Method Thirty-five full-length pk41 sequences from clinical isolates of Malaysia along with four laboratory lines (along with H-strain) were downloaded from public databases. For comparative analysis between species, orthologous P41 genes from P. falciparum, P. vivax, P. coatneyi and P. cynomolgi were also downloaded. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. Phylogenetic relationships between Pk41 genes were determined using MEGA 5.0 software. Results Analysis of 39 full-length pk41 sequences along with the H-strain identified 36 SNPs (20 non-synonymous and 16 synonymous substitutions) resulting in 31 haplotypes. Nucleotide diversity across the full-length gene was low and was similar to its ortholog in P. vivax; pv41. Domain-wise amino acid analysis of the two s48/45 domains indicated low level of polymorphisms for both the domains, and the glutamic acid rich region had extensive size variations. In the central domain, upstream to the glutamate rich region, a unique two to six (K-E)n repeat region was identified within the clinical isolates. Overall, the pk41 genes were indicative of negative/purifying selection due to functional constraints. Domain-wise analysis of the s48/45 domains also indicated purifying selection. However, analysis of Tajima’s D across the genes identified non-synonymous SNPs in the s48/45 domain II with high positive values indicating possible epitope binding regions. All the 6-cysteine residues within the s48/45 domains were conserved within the clinical isolates indicating functional conservation of these regions. Phylogenetic analysis of full-length pk41 genes indicated geographical clustering and identified three subpopulations of P. knowlesi; one originating in the laboratory lines and two originating from Sarawak, Malaysian Borneo. Conclusion This is the first study to report on the polymorphism and natural selection of pk41 genes from clinical isolates of Malaysia. The results reveal that there is low level of polymorphism in both s48/45 domains, indicating that this antigen could be a potential vaccine target. However, genetic and molecular immunology studies involving higher number of samples from various parts of Malaysia would be necessary to validate this antigen’s candidacy as a vaccine target for P. knowlesi.
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pubPeerJ, Inc.
doi10.7717/peerj.6141
urlhttp://search.proquest.com/docview/2156358283/
volume6
pagese6141
issue12
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date2018-12-14