title: Genetic diversity and natural selection of Duffy binding protein of Plasmodium vivax Korean isolates.
abstract: Plasmodium vivax Duffy binding protein (PvDBP) is a micronemal type I membrane protein that plays an essential role in erythrocyte invasion of merozoites. PvDBP is a prime blood stage vaccine candidate antigen against P. vivax, but its polymorphic nature represents a major obstacle to the successful design of a protective vaccine against vivax malaria. In this study, we analyzed the genetic polymorphism and natural selection at the N-terminal cysteine-rich region of PvDBP (PvDBPII) among 70 P. vivax isolates collected from Korean patients during 2005-2010. Seventeen single nucleotide polymorphisms (SNP), which resulted in 14 non-synonymous and 3 synonymous mutations, were found in PvDBPII among the Korean P. vivax isolates. Sequence analyses revealed that 13 different PvDBPII haplotypes, which were clustered into 3 distinct clades, were identified in Korean P. vivax isolates. The difference between the rates of nonsynomyous and synonymous mutations suggested that the region has evolved under natural selection. High selective pressure preferentially acted on regions identified or predicted to be B- and T-cell epitopes and MHC binding regions of PvDBPII. Recombination may also contribute to genetic diversity of PvDBPII. Our results suggest that PvDBPII of Korean P. vivax isolates display a limited genetic polymorphism and are under selective pressure. These results have significant implications for understanding the nature of the P. vivax population circulating in Korea and provide useful information for development of malaria vaccines based on this antigen.
authors.affiliation: Department of Parasitology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Hye-Lim
authors.initials: HL
authors.lastname: Ju
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Kang
authors.forename: Sung-Ung
authors.initials: SU
authors.lastname: Moon
authors.forename: Young-Yil
authors.initials: YY
authors.lastname: Bahk
authors.forename: Pyo-Yun
authors.initials: PY
authors.lastname: Cho
authors.forename: Woon-Mok
authors.initials: WM
authors.lastname: Sohn
authors.forename: Yun-Kyu
authors.initials: YK
authors.lastname: Park
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Tong-Soo
authors.initials: TS
authors.lastname: Kim
authors.forename: Byoung-Kuk
authors.initials: BK
authors.lastname: Na
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D006801:Humans; D016780:Malaria, Vivax / Q000469:parasitology; D008969:Molecular Sequence Data; D010966:Plasmodium vivax / Q000235:genetics* / Q000302:isolation & purification; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D011995:Recombination, Genetic; D056910:Republic of Korea; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D000953:Antigens, Protozoan; C066001:Duffy antigen binding protein, Plasmodium; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface