title: Genetic evidence for contribution of human dispersal to the genetic diversity of EBA-175 in Plasmodium falciparum.
abstract: BACKGROUND
  The 175-kDa erythrocyte binding antigen (EBA-175) of Plasmodium falciparum plays a crucial role in merozoite invasion into human erythrocytes. EBA-175 is believed to have been under diversifying selection; however, there have been no studies investigating the effect of dispersal of humans out of Africa on the genetic variation of EBA-175 in P. falciparum.
  
  
  METHODS
  The PCR-direct sequencing was performed for a part of the eba-175 gene (regions II and III) using DNA samples obtained from Thai patients infected with P. falciparum. The divergence times for the P. falciparum eba-175 alleles were estimated assuming that P. falciparum/Plasmodium reichenowi divergence occurred 6 million years ago (MYA). To examine the possibility of diversifying selection, nonsynonymous and synonymous substitution rates for Plasmodium species were also estimated.
  
  
  RESULTS
  A total of 32 eba-175 alleles were identified from 131 Thai P. falciparum isolates. Their estimated divergence time was 0.13-0.14 MYA, before the exodus of humans from Africa. A phylogenetic tree for a large sequence dataset of P. falciparum eba-175 alleles from across the world showed the presence of a basal Asian-specific cluster for all P. falciparum sequences. A markedly more nonsynonymous substitutions than synonymous substitutions in region II in P. falciparum was also detected, but not within Plasmodium species parasitizing African apes, suggesting that diversifying selection has acted specifically on P. falciparum eba-175.
  
  
  CONCLUSIONS
  Plasmodium falciparum eba-175 genetic diversity appeared to increase following the exodus of Asian ancestors from Africa. Diversifying selection may have played an important role in the diversification of eba-175 allelic lineages. The present results suggest that the dispersals of humans out of Africa influenced significantly the molecular evolution of P. falciparum EBA-175.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. hyasukou@proof.ocn.ne.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yasukochi
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. izumin-tky@umin.ac.jp.|Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. izumin-tky@umin.ac.jp.
authors.forename: Izumi
authors.initials: I
authors.lastname: Naka
authors.affiliation: Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. jintana.pat@mahidol.ac.th.
authors.forename: Jintana
authors.initials: J
authors.lastname: Patarapotikul
authors.affiliation: Department of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. hathairad.han@mahidol.ac.th.
authors.forename: Hathairad
authors.initials: H
authors.lastname: Hananantachai
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. juno-tky@umin.ac.jp.|Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. juno-tky@umin.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000145:classification / Q000235:genetics*; D001483:Base Sequence; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation / Q000235:genetics*; D006071:Gorilla gorilla / Q000469:parasitology; D006801:Humans; D008288:Malaria / Q000469:parasitology; D016778:Malaria, Falciparum / Q000469:parasitology*; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000469:parasitology; D010802:Phylogeny; D010961:Plasmodium / Q000145:classification / Q000235:genetics; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics*; D015800:Protozoan Proteins / Q000145:classification / Q000235:genetics*; D016415:Sequence Alignment; D013785:Thailand
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C065668:erythrocyte-binding antigen 175, Plasmodium