PMID- 33653360 OWN - NLM STAT- MEDLINE DCOM- 20210310 LR - 20210310 IS - 1475-2875 (Electronic) IS - 1475-2875 (Linking) VI - 20 IP - 1 DP - 2021 Mar 2 TI - 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. PG - 124 LID - 10.1186/s12936-021-03664-8 [doi] LID - 124 AB - 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 pi 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 (DeltaDeltaG > 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. FAU - Lin, Li-Yun AU - Lin LY AD - School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong, People's Republic of China. FAU - Huang, Hui-Ying AU - Huang HY AD - Department of Medical Laboratory, Chaozhou People's Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People's Republic of China. AD - Shantou University Medical College, Shantou, Guangdong, People's Republic of China. FAU - Liang, Xue-Yan AU - Liang XY AD - Department of Medical Laboratory, Huizhou Central Hospital, Huizhou, Guangdong, People's Republic of China. FAU - Xie, Dong-De AU - Xie DD AD - Department of Medical Laboratory, Foshan Second People's Hospital, Foshan, Guangdong, People's Republic of China. AD - The Chinese Medical Aid Team To the Republic of Equatorial Guinea, Guangzhou, Guangdong, People's Republic of China. FAU - Chen, Jiang-Tao AU - Chen JT AD - Department of Medical Laboratory, Huizhou Central Hospital, Huizhou, Guangdong, People's Republic of China. AD - The Chinese Medical Aid Team To the Republic of Equatorial Guinea, Guangzhou, Guangdong, People's Republic of China. FAU - Wei, Hua-Gui AU - Wei HG AD - School of Clinical Medicine, Youjiang Medical University for Nationalities, Baise, China. FAU - Huang, Wei-Yi AU - Huang WY AD - School of Clinical Medicine, Youjiang Medical University for Nationalities, Baise, China. FAU - Ehapo, Carlos Salas AU - Ehapo CS AD - Department of Medical Laboratory, Malabo Regional Hospital, Malabo, Equatorial Guinea. FAU - Eyi, Urbano Monsuy AU - Eyi UM AD - Department of Medical Laboratory, Malabo Regional Hospital, Malabo, Equatorial Guinea. FAU - Li, Jian AU - Li J AD - Department of Human Parasitology, School of Basic Medical Sciences, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China. AD - Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China. FAU - Wang, Jun-Li AU - Wang JL AD - School of Clinical Medicine, Youjiang Medical University for Nationalities, Baise, China. FAU - Zheng, Yu-Zhong AU - Zheng YZ AD - School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong, People's Republic of China. FAU - Zha, Guang-Cai AU - Zha GC AD - School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong, People's Republic of China. FAU - Wang, Yu-Ling AU - Wang YL AD - School of Clinical Medicine, Youjiang Medical University for Nationalities, Baise, China. FAU - Chen, Wei-Zhong AU - Chen WZ AD - Department of Medical Laboratory, Chaozhou People's Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People's Republic of China. AD - Shantou University Medical College, Shantou, Guangdong, People's Republic of China. FAU - Liu, Xiang-Zhi AU - Liu XZ AD - Department of Medical Laboratory, Chaozhou People's Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People's Republic of China. AD - Shantou University Medical College, Shantou, Guangdong, People's Republic of China. FAU - Mo, Huan-Tong AU - Mo HT AD - Department of Medical Laboratory, Chaozhou People's Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People's Republic of China. AD - Shantou University Medical College, Shantou, Guangdong, People's Republic of China. FAU - Chen, Xin-Yao AU - Chen XY AD - Department of Medical Laboratory, Chaozhou People's Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People's Republic of China. AD - Shantou University Medical College, Shantou, Guangdong, People's Republic of China. FAU - Lin, Min AU - Lin M AUID- ORCID: 0000-0002-0025-6167 AD - School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou, Guangdong, People's Republic of China. konfutea@hotmail.com. AD - Department of Medical Laboratory, Chaozhou People's Hospital Affiliated to Shantou University Medical College, Chaozhou, Guangdong, People's Republic of China. konfutea@hotmail.com. AD - Shantou University Medical College, Shantou, Guangdong, People's Republic of China. konfutea@hotmail.com. LA - eng GR - 2019-GDXK-0031/Key scientific research projects of Guangdong Provincial Department of Education/ GR - 2019JJD140052/Guangxi Key Research and Development Foundation/ GR - AB18221029/Guangxi Key Research and Development Foundation/ GR - CZK20200602/Special technology program of Chaozhou for novel coronavirus infection control/ GR - CZK20200603/Special technology program of Chaozhou for novel coronavirus infection control/ GR - 2020KZDZX1146/Special research project of Guangdong for Novel coronavirus pneumonia epidemic prevention and contro/ PT - Journal Article DEP - 20210302 PL - England TA - Malar J JT - Malaria journal JID - 101139802 RN - 0 (Epitopes) RN - 0 (Malaria Vaccines) RN - 0 (Protozoan Proteins) RN - 120300-02-9 (thrombospondin-related adhesive protein, protozoan) SB - IM MH - Epitopes MH - Equatorial Guinea/epidemiology MH - Gene Frequency MH - Genetic Variation MH - Haplotypes MH - Humans MH - Malaria Vaccines MH - Malaria, Falciparum/epidemiology/immunology/*parasitology MH - Plasmodium falciparum/*genetics/immunology MH - Polymorphism, Genetic MH - Protozoan Proteins/chemistry/*genetics/immunology MH - Selection, Genetic PMC - PMC7922716 OTO - NOTNLM OT - Bioko Island OT - Genetic diversity OT - Malaria OT - Natural selection OT - Plasmodium falciparum thrombospondin-related adhesive protein (PfTRAP) OT - Vaccine candidate COIS- The authors declare that they have no competing interests. EDAT- 2021/03/04 06:00 MHDA- 2021/03/11 06:00 PMCR- 2021/03/02 CRDT- 2021/03/03 05:34 PHST- 2020/11/19 00:00 [received] PHST- 2021/02/23 00:00 [accepted] PHST- 2021/03/03 05:34 [entrez] PHST- 2021/03/04 06:00 [pubmed] PHST- 2021/03/11 06:00 [medline] PHST- 2021/03/02 00:00 [pmc-release] AID - 10.1186/s12936-021-03664-8 [pii] AID - 3664 [pii] AID - 10.1186/s12936-021-03664-8 [doi] PST - epublish SO - Malar J. 2021 Mar 2;20(1):124. doi: 10.1186/s12936-021-03664-8.