Li-Yun Lin1, Hui-Ying Huang2,3, Xue-Yan Liang4, Dong-De Xie5,6, Jiang-Tao Chen4,6, Hua-Gui Wei7, Wei-Yi Huang7, Carlos Salas Ehapo8, Urbano Monsuy Eyi8, Jian Li9,10, Jun-Li Wang7, Yu-Zhong Zheng1, Guang-Cai Zha1, Yu-Ling Wang7, Wei-Zhong Chen2,3, Xiang-Zhi Liu2,3, Huan-Tong Mo2,3, Xin-Yao Chen2,3, Min Lin11,12,13. 1. School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong, People's Republic of China. 2. Department of Medical Laboratory, Chaozhou People's Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People's Republic of China. 3. Shantou University Medical College, Shantou, Guangdong, People's Republic of China. 4. Department of Medical Laboratory, Huizhou Central Hospital, Huizhou, Guangdong, People's Republic of China. 5. Department of Medical Laboratory, Foshan Second People's Hospital, Foshan, Guangdong, People's Republic of China. 6. The Chinese Medical Aid Team To the Republic of Equatorial Guinea, Guangzhou, Guangdong, People's Republic of China. 7. School of Clinical Medicine, Youjiang Medical University for Nationalities, Baise, China. 8. Department of Medical Laboratory, Malabo Regional Hospital, Malabo, Equatorial Guinea. 9. Department of Human Parasitology, School of Basic Medical Sciences, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China. 10. Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China. 11. School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong, People's Republic of China. konfutea@hotmail.com. 12. Department of Medical Laboratory, Chaozhou People's Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People's Republic of China. konfutea@hotmail.com. 13. Shantou University Medical College, Shantou, Guangdong, People's Republic of China. konfutea@hotmail.com.
Abstract
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: 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: 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: 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.
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: 153 blood spot samples from Bioko malariapatients 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: 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: 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.
Authors: Saad M Bin Dajem; Md Atique Ahmed; Fatimah F Alghnnam; Shouq F Alghannam; Gauspasha Yusuf Deshmukh; Rehan Haider Zaidi; Marie Fe F Bohol; Syeda Sabiha Salam; Syeda Wasfeea Wazid; Mohammed I Shafeai; Fuad H Rudiny; Ali M Motaen; Kareem Morsy; Ahmed A Al-Qahtani Journal: Genes (Basel) Date: 2022-06-25 Impact factor: 4.141