title: Genetic diversity of transmission-blocking vaccine candidate Pvs48/45 in Plasmodium vivax populations in China.
abstract: BACKGROUND
  The male gamete fertilization factor P48/45 in malaria parasites is a prime transmission-blocking vaccine (TBV) candidate. Efforts to develop antimalarial vaccines are often thwarted by genetic diversity of the target antigens. Here we evaluated the genetic diversity of Pvs48/45 gene in global Plasmodium vivax populations.
  
  
  METHODS
  We determined 200 Pvs48/45 sequences collected from temperate and subtropical parasite populations in China. Population genetic and evolutionary analyses were performed to determine the levels of genetic diversity, potential signature of selection, and population differentiation.
  
  
  RESULTS
  Analysis of the Pvs48/45 sequences from 200 P. vivax parasites collected in a temperate and a tropical region revealed a low level of genetic diversity (π = 0.0012) with 14 single nucleotide polymorphisms, of which 11 were nonsynonymous. Analysis of 344 Pvs48/45 sequences from nine worldwide P. vivax populations detected a total of 38 haplotypes, of which 13 haplotypes were present only once. Multiple tests for selection confirmed a signature of positive selection on Pvs48/45 with selection skewed to the second cysteine domain. Haplotype network analysis and Wright's fixation index showed large geographical differentiation with the presence of continent-or region-specific mutations in this gene.
  
  
  CONCLUSIONS
  Pvs48/45 displays low levels of genetic diversity with the presence of region-specific mutations. Some of the mutations may be potential epitope targets based on their positions in the predicted structure, highlighting the need for future evaluation of these mutations in designing Pvs48/45-based TBV.
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. fenghuisy@yahoo.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Entomology, Pennsylvania State University, 501 ASI Building, University Park, PA, 16802, USA. bhavnaguptaster@gmail.com.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Gupta
authors.affiliation: Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. bigwangfei@qq.com.
authors.forename: Meilian
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. 470057427@qq.com.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. zlicmu@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. piggytongtongwow@hotmail.com.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Parasitology, College of Basic Medical Sciences, Dali Medical College, Dali, Yunnan, China. yym0408@163.com.
authors.forename: Yimei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Parasitology, Bengbu Medical College, Anhui, China. fq333@sohu.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. enjie359@126.com.
authors.forename: Enjie
authors.initials: E
authors.lastname: Luo
authors.affiliation: Dalian Institute of Biotechnology, Dalian, Liaoning, China. qifan10001@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Cell-free Science and Technology Research Center, Ehime University, Matsuyama, Ehime, 790-8577, Japan. takafumi.mb@ehime-u.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. ymcao@mail.cmu.edu.cn.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China. luc2@psu.edu.|Department of Entomology, Pennsylvania State University, 501 ASI Building, University Park, PA, 16802, USA. luc2@psu.edu.
authors.forename: Liwang
authors.initials: L
authors.lastname: Cui
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology; D002681:China; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation; D006239:Haplotypes; D008969:Molecular Sequence Data; D058974:Phylogeography; D010966:Plasmodium vivax / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D016052:Protozoan Vaccines / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D000939:Epitopes; D016052:Protozoan Vaccines