title: Size polymorphism and low sequence diversity in the locus encoding the Plasmodium vivax rhoptry neck protein 4 (PvRON4) in Colombian isolates.
abstract: BACKGROUND
  Designing a vaccine against Plasmodium vivax has focused on selecting antigens involved in invasion mechanisms that must have domains with low polymorphism for avoiding allele-specific immune responses. The rhoptry neck protein 4 (RON4) forms part of the tight junction, which is essential in the invasion of hepatocytes and/or erythrocytes; however, little is known about this locus' genetic diversity.
  
  
  METHODS
  DNA sequences from 73 Colombian clinical isolates from pvron4 gene were analysed for characterizing their genetic diversity; pvron4 haplotype number and distribution, as well as the evolutionary forces determining diversity pattern, were assessed by population genetics and molecular evolutionary approaches.
  
  
  RESULTS
  ron4 has low genetic diversity in P. vivax at sequence level; however, a variable amount of tandem repeats at the N-terminal region leads to extensive size polymorphism. This region seems to be exposed to the immune system. The central region has a putative esterase/lipase domain which, like the protein's C-terminal fragment, is highly conserved at intra- and inter-species level. Both regions are under purifying selection.
  
  
  CONCLUSIONS
  pvron4 is the locus having the lowest genetic diversity described to date for P. vivax. The repeat regions in the N-terminal region could be associated with immune evasion mechanisms while the central region and the C-terminal region seem to be under functional or structural constraint. Bearing such results in mind, the PvRON4 central and/or C-terminal portions represent promising candidates when designing a subunit-based vaccine as they are aimed at avoiding an allele-specific immune response, which might limit vaccine efficacy.
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50 No. 26-20, Bogotá D.C., Colombia.|Microbiology Postgraduate Program, Universidad Nacional de Colombia, Bogotá D.C., Colombia.
authors.forename: Sindy P
authors.initials: SP
authors.lastname: Buitrago
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50 No. 26-20, Bogotá D.C., Colombia.|School of Medicine and Health Sciences, Universidad del Rosario, Bogotá D.C., Colombia.
authors.forename: Diego
authors.initials: D
authors.lastname: Garzón-Ospina
authors.affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50 No. 26-20, Bogotá D.C., Colombia. mapatarr.fidic@gmail.com.|School of Medicine and Health Sciences, Universidad del Rosario, Bogotá D.C., Colombia. mapatarr.fidic@gmail.com.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Patarroyo
mesh_terms: D000293:Adolescent; D000328:Adult; D016000:Cluster Analysis; D003105:Colombia; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D016780:Malaria, Vivax / Q000469:parasitology*; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D010966:Plasmodium vivax / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D055815:Young Adult
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins
keywords: Functional restriction; Genetic diversity; Natural selection; Plasmodium vivax; Rhoptry; Tandem repeat; pvron4