title: Population genetic structure and natural selection of apical membrane antigen-1 in Plasmodium vivax Korean isolates.
abstract: BACKGROUND
  Plasmodium vivax apical membrane antigen-1 (PvAMA-1) is a leading candidate antigen for blood stage malaria vaccine. However, antigenic variation is a major obstacle in the development of an effective vaccine based on this antigen. In this study, the genetic structure and the effect of natural selection of PvAMA-1 among Korean P. vivax isolates were analysed.
  
  
  METHODS
  Blood samples were collected from 66 Korean patients with vivax malaria. The entire PvAMA-1 gene was amplified by polymerase chain reaction and cloned into a TA cloning vector. The PvAMA-1 sequence of each isolate was sequenced and the polymorphic characteristics and effect of natural selection were analysed using the DNASTAR, MEGA4, and DnaSP programs.
  
  
  RESULTS
  Thirty haplotypes of PvAMA-1, which were further classified into seven different clusters, were identified in the 66 Korean P. vivax isolates. Domain II was highly conserved among the sequences, but substantial nucleotide diversity was observed in domains I and III. The difference between the rates of non-synonymous and synonymous mutations suggested that the gene has evolved under natural selection. No strong evidence indicating balancing or positive selection on PvAMA-1 was identified. Recombination may also play a role in the resulting genetic diversity of PvAMA-1.
  
  
  CONCLUSIONS
  This study is the first comprehensive analysis of nucleotide diversity across the entire PvAMA-1 gene using a single population sample from Korea. Korean PvAMA-1 had limited genetic diversity compared to PvAMA-1 in global isolates. The overall pattern of genetic polymorphism of Korean PvAMA-1 differed from other global isolates and novel amino acid changes were also identified in Korean PvAMA-1. Evidences for natural selection and recombination event were observed, which is likely to play an important role in generating genetic diversity across the PvAMA-1. These results provide useful information for the understanding the population structure of P. vivax circulating in Korea and have important implications for the design of a vaccine incorporating PvAMA-1.
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, 660-751, Republic of Korea. gjm9951001@hanmail.net.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Kang
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, 660-751, Republic of Korea. jylee5492@gmail.com.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Tropical Medicine, Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, 400-712, Republic of Korea. chopy74@hanmail.net.
authors.forename: Pyo-Yun
authors.initials: PY
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 463-707, Republic of Korea. mboy2@korea.com.
authors.forename: Sung-Ung
authors.initials: SU
authors.lastname: Moon
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, 660-751, Republic of Korea. seses13@nate.com.
authors.forename: Hye-Lim
authors.initials: HL
authors.lastname: Ju
authors.affiliation: Department of Tropical Medicine, Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, 400-712, Republic of Korea. asksay@daum.net.
authors.forename: Seong Kyu
authors.initials: SK
authors.lastname: Ahn
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, 660-751, Republic of Korea. wmsohn@gnu.ac.kr.
authors.forename: Woon-Mok
authors.initials: WM
authors.lastname: Sohn
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, J-566, 1275 Center Drive, Gainesville, FL, 32610, USA. rainlee67@naver.com.
authors.forename: Hyeong-Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Tropical Medicine, Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, 400-712, Republic of Korea. tongsookim@inha.ac.kr.
authors.forename: Tong-Soo
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Department of Parasitology and Tropical Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, 660-751, Republic of Korea. bkna@gnu.ac.kr.
authors.forename: Byoung-Kuk
authors.initials: BK
authors.lastname: Na
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D005822:Genetic Vectors; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D007723:Korea; D016780:Malaria, Vivax / Q000469:parasitology; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010966:Plasmodium vivax / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics*; D011995:Recombination, Genetic; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium