Abstract
BackgroundThrombospondin-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.Methods153 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.ResultsA 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.ConclusionsEvidences 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.
Highlights
Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells
Evidences in the present investigation supported that Plasmodium falciparum thrombospondin-related adhesive protein (PfTRAP) gene from Bioko Island and other malaria endemic countries is highly polymorphic, which provided the genetic information back‐ ground for developing an PfTRAP-based universal effective vaccine
Malaria patients were classified into uncomplicated malaria states according to World Health Organization (WHO) criteria, which were defined as positive smear for P. falciparum and presence of fever (≥ 37.5 °C)
Summary
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. Malaria is a major public health threat in many parts of the globe and is responsible for half a million deaths annually. Plasmodium falciparum is the parasite that cause 99.7% malaria cases in African regions [1]. The sub-Saharan African country, Equatorial Guinea has a total population of 1.31 million (2018). An island of Equatorial Guinea off the coast of Cameroon, with historically high malaria transmission. Evaluations indicated that malaria prevalence had dropped considerably from 43.3 to 10.5% between 2004 and 2016, resulting in a 13.3% reduction of moderate to severe anaemia in children aged 1–5 years. Despite considerable success in reducing the burden on the island, malaria is still a major public health concern in Bioko Island
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