title: Spatial variation in genetic diversity and natural selection on the thrombospondin-related adhesive protein locus of Plasmodium vivax (PvTRAP).
abstract: Thrombospondin-related adhesive protein (TRAP) of malaria parasites is essential for sporozoite motility and invasions into mosquito's salivary gland and vertebrate's hepatocyte; thereby, it is a promising target for pre-erythrocytic vaccine. TRAP of Plasmodium vivax (PvTRAP) exhibits sequence heterogeneity among isolates, an issue relevant to vaccine development. To gain insights into variation in the complete PvTRAP sequences of parasites in Thailand, 114 vivax malaria patients were recruited in 2006-2007 from 4 major endemic provinces bordering Myanmar (Tak in the northwest, n = 30 and Prachuap Khirikhan in the southwest, n = 25), Cambodia (Chanthaburi in the east, n = 29) and Malaysia (Yala and Narathiwat in the south, n = 30). In total, 26 amino acid substitutions were detected and 9 of which were novel, resulting in 44 distinct haplotypes. Haplotype and nucleotide diversities were lowest in southern P. vivax population while higher levels of diversities were observed in other populations. Evidences of positive selection on PvTRAP were demonstrated in domains II and IV and purifying selection in domains I, II and VI. Genetic differentiation was significant between each population except that between populations bordering Myanmar where transmigration was common. Regression analysis of pairwise linearized Fst and geographic distance suggests that P. vivax populations in Thailand have been isolated by distance. Sequence diversity of PvTRAP seems to be temporally stable over one decade in Tak province based on comparison of isolates collected in 1996 (n = 36) and 2006-2007. Besides natural selection, evidences of intragenic recombination have been supported in this study that could maintain and further generate diversity in this locus. It remains to be investigated whether amino acid substitutions in PvTRAP could influence host immune responses although several predicted variant T cell epitopes drastically altered the epitope scores. Knowledge on geographic diversity in PvTRAP constitutes an important basis for vaccine design provided that vaccination largely confers variant-specific immunity.
authors.affiliation: Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Rattiporn
authors.initials: R
authors.lastname: Kosuwin
authors.affiliation: Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Chaturong
authors.initials: C
authors.lastname: Putaporntip
authors.affiliation: Department of Infectious Diseases, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tachibana
authors.affiliation: Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Somchai
authors.initials: S
authors.lastname: Jongwutiwes
mesh_terms: D000595:Amino Acid Sequence; D016000:Cluster Analysis; D016054:DNA, Protozoan / Q000302:isolation & purification / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D016780:Malaria, Vivax / Q000175:diagnosis / Q000469:parasitology; D009154:Mutation; D010802:Phylogeny; D010966:Plasmodium vivax / Q000302:isolation & purification / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D012044:Regression Analysis; D012641:Selection, Genetic
chemical_list: D016054:DNA, Protozoan; D018984:Epitopes, T-Lymphocyte; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan