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

Malaria Journal

Jian Li¹  Wei-Zhong Chen²  Xiang-Zhi Liu²  Xin-Yao Chen²  Huan-Tong Mo²  Hui-Ying Huang²  Dong-De Xie³  Xue-Yan Liang⁴  Jiang-Tao Chen⁵  Carlos Salas Ehapo⁶  Urbano Monsuy Eyi⁶  Hua-Gui Wei⁷  Jun-Li Wang⁷  Wei-Yi Huang⁷  Yu-Ling Wang⁷  Li-Yun Lin⁸  Yu-Zhong Zheng⁸  Guang-Cai Zha⁸  Min Lin⁹ 

[1] Department of Human Parasitology, School of Basic Medical Sciences, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China;Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China;Department of Medical Laboratory, Chaozhou People’s Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People’s Republic of China;Shantou University Medical College, Shantou, Guangdong, People’s Republic of China;Department of Medical Laboratory, Foshan Second People’s Hospital, Foshan, Guangdong, People’s Republic of China;The Chinese Medical Aid Team To the Republic of Equatorial Guinea, Guangzhou, Guangdong, People’s Republic of China;Department of Medical Laboratory, Huizhou Central Hospital, Huizhou, Guangdong, People’s Republic of China;Department of Medical Laboratory, Huizhou Central Hospital, Huizhou, Guangdong, People’s Republic of China;The Chinese Medical Aid Team To the Republic of Equatorial Guinea, Guangzhou, Guangdong, People’s Republic of China;Department of Medical Laboratory, Malabo Regional Hospital, Malabo, Equatorial Guinea;School of Clinical Medicine, Youjiang Medical University for Nationalities, Baise, China;School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong, People’s Republic of China;School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong, People’s Republic of China;Department of Medical Laboratory, Chaozhou People’s Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People’s Republic of China;Shantou University Medical College, Shantou, Guangdong, People’s Republic of China;

关键词: Plasmodium falciparum;    Genetic diversity;    Natural selection;    Bioko Island;    Malaria;    Vaccine candidate;   

DOI  :  10.1186/s12936-021-03664-8

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY