Genetic diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum on Bioko Island, Equatorial Guinea and global comparative analysis.
Bioko Island
Genetic diversity
Malaria
Natural selection
Plasmodium falciparum thrombospondin-related adhesive protein (PfTRAP)
Vaccine candidate
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
02 Mar 2021
02 Mar 2021
Historique:
received:
19
11
2020
accepted:
23
02
2021
entrez:
3
3
2021
pubmed:
4
3
2021
medline:
11
3
2021
Statut:
epublish
Résumé
Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. 153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.
Sections du résumé
BACKGROUND
BACKGROUND
Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described.
METHODS
METHODS
153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools.
RESULTS
RESULTS
A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure.
CONCLUSIONS
CONCLUSIONS
Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.
Identifiants
pubmed: 33653360
doi: 10.1186/s12936-021-03664-8
pii: 10.1186/s12936-021-03664-8
pmc: PMC7922716
doi:
Substances chimiques
Epitopes
0
Malaria Vaccines
0
Protozoan Proteins
0
thrombospondin-related adhesive protein, protozoan
120300-02-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
124Subventions
Organisme : Key scientific research projects of Guangdong Provincial Department of Education
ID : 2019-GDXK-0031
Organisme : Guangxi Key Research and Development Foundation
ID : 2019JJD140052
Organisme : Guangxi Key Research and Development Foundation
ID : AB18221029
Organisme : Special technology program of Chaozhou for novel coronavirus infection control
ID : CZK20200602
Organisme : Special technology program of Chaozhou for novel coronavirus infection control
ID : CZK20200603
Organisme : Special research project of Guangdong for Novel coronavirus pneumonia epidemic prevention and contro
ID : 2020KZDZX1146
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