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Diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium knowlesi in Malaysia

Background Plasmodium knowlesi a parasite of the macaques is currently the most common cause of human malaria in Malaysia. The thrombospondin-related adhesive protein (TRAP) gene is pre-erythrocytic stage antigen. It is a well-characterized vaccine candidate in Plasmodium vivax and Plasmodium falcip... Full description

Journal Title: Malaria Journal 2018, Vol.17
Main Author: Lau, Yee
Other Authors: Fu-Shi, Quan
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 14752875 ; DOI: 10.1186/s12936-018-2423-1
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title: Diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium knowlesi in Malaysia
format: Article
creator:
  • Lau, Yee
  • Fu-Shi, Quan
subjects:
  • Malaysia
  • Borneo
  • Plasmodium Knowlesi
  • Plasmodium Falciparum
  • Plasmodium Vivax
  • Plasmodium Coatneyi
  • Infections
  • Population
  • Malaria
  • Vaccines
  • Natural Selection
  • Proteins
  • Phylogenetics
  • Hypothesis Testing
  • Bioinformatics
  • Parasites
  • Studies
  • Acid Phosphatase (Tartrate-Resistant)
  • Adhesives
  • Antigens
  • Genetic Diversity
  • Genes
  • Haplotypes
  • Natural Selection
  • Motility
  • Thrombospondin-Related Adhesive Protein
  • Proteins
  • Immune Response
  • Analysis
  • Population Differentiation
  • Strain
  • Phylogenetics
  • Disease Control
  • Public Health
  • Identification
  • Antigens
  • Haplotypes
  • Defence Mechanisms
  • Genetic Diversity
  • Malaria
  • Samples
  • Population Genetics
  • Immune Response
  • Human Diseases
  • Proline
  • Vector-Borne Diseases
  • Adhesives
  • Immunity
  • Proline
  • Clinical Isolates
  • Genes
  • Asparagine
  • Gene Polymorphism
  • Vaccines
  • Population Differentiation
  • Length
  • Software
  • Adhesives
  • Malaria
  • Von Willebrand Factor
  • Vaccines
  • Phylogeny
  • Genetic Diversity
  • Malaria
  • Computer Programs
  • Haplotypes
  • Single-Nucleotide Polymorphism
  • Nucleotide Sequence
  • Nucleotides
  • Genetic Diversity
  • Species Interactions: Parasites and Diseases
ispartof: Malaria Journal, 2018, Vol.17
description: Background Plasmodium knowlesi a parasite of the macaques is currently the most common cause of human malaria in Malaysia. The thrombospondin-related adhesive protein (TRAP) gene is pre-erythrocytic stage antigen. It is a well-characterized vaccine candidate in Plasmodium vivax and Plasmodium falciparum, however, no study has been done in the orthologous gene of P. knowlesi. This study investigates nucleotide diversity, haplotypes, natural selection and population differentiation of full-length pktrap genes in clinical samples from Malaysia. Methods Forty full-length pktrap sequences from clinical isolates of Malaysia along with the reference H-strain were downloaded from published databases. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. McDonald–Kreitman test was conducted using P. vivax and Plasmodium coatneyi as ortholog sequence in DnaSP 5.10 software. Population genetic differentiation index (FST) of parasite populations was determined using Arlequin v3.5. Phylogenetic relationships between trap ortholog genes were determined using MEGA 5.0 software. Results Comparison of 40 full-length pktrap sequences along with the H-strain identified 74 SNPs (53 non-synonymous and 21 synonymous substitutions) resulting in 29 haplotypes. Analysis of the full-length gene showed that the nucleotide diversity was lower compared to its nearest ortholog pvtrap. Domain-wise analysis indicated that the proline/asparagine rich region had higher nucleotide diversity compared to the von Willebrand factor domain and the thrombospondin-type-1 domain. McDonald–Kreitman test identified that the ratio of the number of nonsynonymous to synonymous polymorphic sites within P. knowlesi was significantly higher than that of the number of nonsynonymous to synonymous fixed sites between P. knowlesi and P. vivax. The von Willebrand factor domain also indicated balancing selection using MK test, however, it did not give significant results when tested with P. coatneyi as an outgroup. Phylogenetic analysis of full-length genes identified three distinct sub-clusters of P. knowlesi, one originating from Peninsular Malaysia and two originating from Malaysian Borneo. High population differentiation values was observed within samples from Peninsular Malaysia and Malaysian Borneo. Conclusions This study is the first to report on the genetic diversity and natural selection of full-length pktrap. Low level of genetic diversity was found
language: eng
source:
identifier: E-ISSN: 14752875 ; DOI: 10.1186/s12936-018-2423-1
fulltext: fulltext_linktorsrc
issn:
  • 14752875
  • 1475-2875
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titleDiversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium knowlesi in Malaysia
creatorLau, Yee ; Fu-Shi, Quan
ispartofMalaria Journal, 2018, Vol.17
identifierE-ISSN: 14752875 ; DOI: 10.1186/s12936-018-2423-1
subjectMalaysia ; Borneo ; Plasmodium Knowlesi ; Plasmodium Falciparum ; Plasmodium Vivax ; Plasmodium Coatneyi ; Infections ; Population ; Malaria ; Vaccines ; Natural Selection ; Proteins ; Phylogenetics ; Hypothesis Testing ; Bioinformatics ; Parasites ; Studies ; Acid Phosphatase (Tartrate-Resistant) ; Adhesives ; Antigens ; Genetic Diversity ; Genes ; Haplotypes ; Natural Selection ; Motility ; Thrombospondin-Related Adhesive Protein ; Proteins ; Immune Response ; Analysis ; Population Differentiation ; Strain ; Phylogenetics ; Disease Control ; Public Health ; Identification ; Antigens ; Haplotypes ; Defence Mechanisms ; Genetic Diversity ; Malaria ; Samples ; Population Genetics ; Immune Response ; Human Diseases ; Proline ; Vector-Borne Diseases ; Adhesives ; Immunity ; Proline ; Clinical Isolates ; Genes ; Asparagine ; Gene Polymorphism ; Vaccines ; Population Differentiation ; Length ; Software ; Adhesives ; Malaria ; Von Willebrand Factor ; Vaccines ; Phylogeny ; Genetic Diversity ; Malaria ; Computer Programs ; Haplotypes ; Single-Nucleotide Polymorphism ; Nucleotide Sequence ; Nucleotides ; Genetic Diversity ; Species Interactions: Parasites and Diseases
descriptionBackground Plasmodium knowlesi a parasite of the macaques is currently the most common cause of human malaria in Malaysia. The thrombospondin-related adhesive protein (TRAP) gene is pre-erythrocytic stage antigen. It is a well-characterized vaccine candidate in Plasmodium vivax and Plasmodium falciparum, however, no study has been done in the orthologous gene of P. knowlesi. This study investigates nucleotide diversity, haplotypes, natural selection and population differentiation of full-length pktrap genes in clinical samples from Malaysia. Methods Forty full-length pktrap sequences from clinical isolates of Malaysia along with the reference H-strain were downloaded from published databases. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. McDonald–Kreitman test was conducted using P. vivax and Plasmodium coatneyi as ortholog sequence in DnaSP 5.10 software. Population genetic differentiation index (FST) of parasite populations was determined using Arlequin v3.5. Phylogenetic relationships between trap ortholog genes were determined using MEGA 5.0 software. Results Comparison of 40 full-length pktrap sequences along with the H-strain identified 74 SNPs (53 non-synonymous and 21 synonymous substitutions) resulting in 29 haplotypes. Analysis of the full-length gene showed that the nucleotide diversity was lower compared to its nearest ortholog pvtrap. Domain-wise analysis indicated that the proline/asparagine rich region had higher nucleotide diversity compared to the von Willebrand factor domain and the thrombospondin-type-1 domain. McDonald–Kreitman test identified that the ratio of the number of nonsynonymous to synonymous polymorphic sites within P. knowlesi was significantly higher than that of the number of nonsynonymous to synonymous fixed sites between P. knowlesi and P. vivax. The von Willebrand factor domain also indicated balancing selection using MK test, however, it did not give significant results when tested with P. coatneyi as an outgroup. Phylogenetic analysis of full-length genes identified three distinct sub-clusters of P. knowlesi, one originating from Peninsular Malaysia and two originating from Malaysian Borneo. High population differentiation values was observed within samples from Peninsular Malaysia and Malaysian Borneo. Conclusions This study is the first to report on the genetic diversity and natural selection of full-length pktrap. Low level of genetic diversity was found across the full-length gene of pktrap. Balancing selection of the von Willebrand factor domain indicated that TRAP could be a target in inducing immune response against P. knowlesi infections. However, higher number of samples would be necessary to further confirm the findings.
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titleDiversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium knowlesi in Malaysia
descriptionBackground Plasmodium knowlesi a parasite of the macaques is currently the most common cause of human malaria in Malaysia. The thrombospondin-related adhesive protein (TRAP) gene is pre-erythrocytic stage antigen. It is a well-characterized vaccine candidate in Plasmodium vivax and Plasmodium falciparum, however, no study has been done in the orthologous gene of P. knowlesi. This study investigates nucleotide diversity, haplotypes, natural selection and population differentiation of full-length pktrap genes in clinical samples from Malaysia. Methods Forty full-length pktrap sequences from clinical isolates of Malaysia along with the reference H-strain were downloaded from published databases. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. McDonald–Kreitman test was conducted using P. vivax and Plasmodium coatneyi as ortholog sequence in DnaSP 5.10 software. Population genetic differentiation index (FST) of parasite populations was determined using Arlequin v3.5. Phylogenetic relationships between trap ortholog genes were determined using MEGA 5.0 software. Results Comparison of 40 full-length pktrap sequences along with the H-strain identified 74 SNPs (53 non-synonymous and 21 synonymous substitutions) resulting in 29 haplotypes. Analysis of the full-length gene showed that the nucleotide diversity was lower compared to its nearest ortholog pvtrap. Domain-wise analysis indicated that the proline/asparagine rich region had higher nucleotide diversity compared to the von Willebrand factor domain and the thrombospondin-type-1 domain. McDonald–Kreitman test identified that the ratio of the number of nonsynonymous to synonymous polymorphic sites within P. knowlesi was significantly higher than that of the number of nonsynonymous to synonymous fixed sites between P. knowlesi and P. vivax. The von Willebrand factor domain also indicated balancing selection using MK test, however, it did not give significant results when tested with P. coatneyi as an outgroup. Phylogenetic analysis of full-length genes identified three distinct sub-clusters of P. knowlesi, one originating from Peninsular Malaysia and two originating from Malaysian Borneo. High population differentiation values was observed within samples from Peninsular Malaysia and Malaysian Borneo. Conclusions This study is the first to report on the genetic diversity and natural selection of full-length pktrap. Low level of genetic diversity was found across the full-length gene of pktrap. Balancing selection of the von Willebrand factor domain indicated that TRAP could be a target in inducing immune response against P. knowlesi infections. However, higher number of samples would be necessary to further confirm the findings.
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19Antigens
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21Genes
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24Thrombospondin-Related Adhesive Protein
25Immune Response
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27Population Differentiation
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35Human Diseases
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42Length
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46Computer Programs
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50Species Interactions: Parasites and Diseases
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citationvol 17
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titleDiversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium knowlesi in Malaysia
authorLau, Yee ; Fu-Shi, Quan
creationdate20180101
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3Plasmodium Falciparum
4Plasmodium Vivax
5Plasmodium Coatneyi
6Infections
7Population
8Malaria
9Vaccines
10Natural Selection
11Proteins
12Phylogenetics
13Hypothesis Testing
14Bioinformatics
15Parasites
16Studies
17Acid Phosphatase (Tartrate-Resistant)
18Adhesives
19Antigens
20Genetic Diversity
21Genes
22Haplotypes
23Motility
24Thrombospondin-Related Adhesive Protein
25Immune Response
26Analysis
27Population Differentiation
28Strain
29Disease Control
30Public Health
31Identification
32Defence Mechanisms
33Samples
34Population Genetics
35Human Diseases
36Proline
37Vector-Borne Diseases
38Immunity
39Clinical Isolates
40Asparagine
41Gene Polymorphism
42Length
43Software
44Von Willebrand Factor
45Phylogeny
46Computer Programs
47Single-Nucleotide Polymorphism
48Nucleotide Sequence
49Nucleotides
50Species Interactions: Parasites and Diseases
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abstractBackground Plasmodium knowlesi a parasite of the macaques is currently the most common cause of human malaria in Malaysia. The thrombospondin-related adhesive protein (TRAP) gene is pre-erythrocytic stage antigen. It is a well-characterized vaccine candidate in Plasmodium vivax and Plasmodium falciparum, however, no study has been done in the orthologous gene of P. knowlesi. This study investigates nucleotide diversity, haplotypes, natural selection and population differentiation of full-length pktrap genes in clinical samples from Malaysia. Methods Forty full-length pktrap sequences from clinical isolates of Malaysia along with the reference H-strain were downloaded from published databases. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. McDonald–Kreitman test was conducted using P. vivax and Plasmodium coatneyi as ortholog sequence in DnaSP 5.10 software. Population genetic differentiation index (FST) of parasite populations was determined using Arlequin v3.5. Phylogenetic relationships between trap ortholog genes were determined using MEGA 5.0 software. Results Comparison of 40 full-length pktrap sequences along with the H-strain identified 74 SNPs (53 non-synonymous and 21 synonymous substitutions) resulting in 29 haplotypes. Analysis of the full-length gene showed that the nucleotide diversity was lower compared to its nearest ortholog pvtrap. Domain-wise analysis indicated that the proline/asparagine rich region had higher nucleotide diversity compared to the von Willebrand factor domain and the thrombospondin-type-1 domain. McDonald–Kreitman test identified that the ratio of the number of nonsynonymous to synonymous polymorphic sites within P. knowlesi was significantly higher than that of the number of nonsynonymous to synonymous fixed sites between P. knowlesi and P. vivax. The von Willebrand factor domain also indicated balancing selection using MK test, however, it did not give significant results when tested with P. coatneyi as an outgroup. Phylogenetic analysis of full-length genes identified three distinct sub-clusters of P. knowlesi, one originating from Peninsular Malaysia and two originating from Malaysian Borneo. High population differentiation values was observed within samples from Peninsular Malaysia and Malaysian Borneo. Conclusions This study is the first to report on the genetic diversity and natural selection of full-length pktrap. Low level of genetic diversity was found across the full-length gene of pktrap. Balancing selection of the von Willebrand factor domain indicated that TRAP could be a target in inducing immune response against P. knowlesi infections. However, higher number of samples would be necessary to further confirm the findings.
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date2018-07-27