title: Diversity and evolutionary genetics of the three major Plasmodium vivax merozoite genes participating in reticulocyte invasion in southern Mexico.
abstract: BACKGROUND
  Reported malaria cases in the Americas had been reduced to about one-half million by 2012. To advance towards elimination of this disease, it is necessary to gain insights into how the malaria parasite is evolving, including the emergence, spread and persistence of new haplotypes in affected regions. In here, the genetic diversity of the three major P. vivax merozoite genes was analyzed.
  
  
  METHODS
  From P. vivax-infected blood samples obtained in southern Mexico (SMX) during 2006-2007, nucleotide sequences were achieved for: the 42 kDa carboxyl fragment of the merozoite surface protein-1 (msp1 42 ), domains I-II of the apical membrane antigen-1 (ama1 I-II ), and domain II of the Duffy binding protein (dbp II ). Gene polymorphism was examined and haplotype networks were developed to depict parasite relationships in SMX. Then genetic diversity, recombination and natural selection were analyzed and the degree of differentiation was determined as FST values.
  
  
  RESULTS
  The diversity of P. vivax merozoite genes in SMX was less than that of parasites from other geographic origins, with dbp II  < ama1 I-II  < msp1 42 . Ama1 I-II and msp1 42 exposed the more numerous haplotypes exclusive to SMX. While, all dbp II haplotypes from SMX were separated from one to three mutational steps, the networks of ama1 I-II and msp1 42 were more complex; loops and numerous mutational steps were evidenced, likely due to recombination. Sings of local diversification were more evident for msp1 42 . Sixteen combined haplotypes were determined; one of these haplotypes not detected in 2006 was highly frequent in 2007. The Rm value was higher for msp1 42 than for ama1 I-II, being insignificant for dbp II . The dN-dS value was highly significant for ama1 I-II and lesser so for dbp II . The F ST values were higher for dbp II than msp1 42 , and very low for ama1 I-II .
  
  
  CONCLUSIONS
  In SMX, P. vivax ama1 I-II , dbp II and msp1 42 demonstrated limited diversity, and exhibited a differentiated parasite population. The results suggest that differential intensities of selective forces are operating on these gene fragments, and probably related to their timing, length of exposure and function during reticulocyte adhesion and invasion. Therefore, these finding are essential for mono and multivalent vaccine development and for epidemiological surveillance.
authors.affiliation: Regional Centre for Research in Public Health, National Institute for Public Health, Tapachula, Chiapas, 30700, Mexico. lgonzal@insp.mx.
authors.forename: Lilia
authors.initials: L
authors.lastname: González-Cerón
authors.affiliation: Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF, 04510, México. renecerritos@gmail.com.
authors.forename: Rene
authors.initials: R
authors.lastname: Cerritos
authors.affiliation: Regional Centre for Research in Public Health, National Institute for Public Health, Tapachula, Chiapas, 30700, Mexico. corzojordan@gmail.com.
authors.forename: Jordán
authors.initials: J
authors.lastname: Corzo-Mancilla
authors.affiliation: Regional Centre for Research in Public Health, National Institute for Public Health, Tapachula, Chiapas, 30700, Mexico. fsantill@insp.mx.
authors.forename: Frida
authors.initials: F
authors.lastname: Santillán
mesh_terms: D000953:Antigens, Protozoan / Q000235:genetics*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes; D008565:Membrane Proteins / Q000235:genetics*; D020066:Merozoite Surface Protein 1 / Q000235:genetics*; D052940:Merozoites / Q000145:classification*; D008800:Mexico; D008969:Molecular Sequence Data; D010966:Plasmodium vivax / Q000145:classification* / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012156:Reticulocytes / Q000469:parasitology*; D017422:Sequence Analysis, DNA
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; C066001:Duffy antigen binding protein, Plasmodium; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C090077:apical membrane antigen I, Plasmodium