title: A human-specific allelic group of the MHC DRB1 gene in primates.
abstract: BACKGROUND
  Diversity among human leukocyte antigen (HLA) molecules has been maintained by host-pathogen coevolution over a long period of time. Reflecting this diversity, the HLA loci are the most polymorphic in the human genome. One characteristic of HLA diversity is long-term persistence of allelic lineages, which causes trans-species polymorphisms to be shared among closely related species. Modern humans have disseminated across the world after their exodus from Africa, while chimpanzees have remained in Africa since the speciation event between humans and chimpanzees. It is thought that modern humans have recently acquired resistance to novel pathogens outside Africa. In the present study, we investigated HLA alleles that could contribute to this local adaptation in humans and also studied the contribution of natural selection to human evolution by using molecular data.
  
  
  RESULTS
  Phylogenetic analysis of HLA-DRB1 genes identified two major groups, HLA Groups A and B. Group A formed a monophyletic clade distinct from DRB1 alleles in other Catarrhini, suggesting that Group A is a human-specific allelic group. Our estimates of divergence time suggested that seven HLA-DRB1 Group A allelic lineages in humans have been maintained since before the speciation event between humans and chimpanzees, while chimpanzees possess only one DRB1 allelic lineage (Patr-DRB1*03), which is a sister group to Group A. Experimental data showed that some Group A alleles bound to peptides derived from human-specific pathogens. Of the Group A alleles, three exist at high frequencies in several local populations outside Africa.
  
  
  CONCLUSIONS
  HLA Group A alleles are likely to have been retained in human lineages for a long period of time and have not expanded since the divergence of humans and chimpanzees. On the other hand, most orthologs of HLA Group A alleles may have been lost in the chimpanzee due to differences in selective pressures. The presence of alleles with high frequency outside of Africa suggests these HLA molecules result from the local adaptations of humans. Our study helps elucidate the mechanism by which the human adaptive immune system has coevolved with pathogens over a long period of time.
authors.affiliation: Molecular and Genetic Epidemiology, Faculty of Medicine, University of Tsukuba, 305-8575 Tsukuba, Ibaraki, Japan. hyasukou@proof.ocn.ne.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yasukochi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Satta
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D059811:HLA-DRB1 Chains / Q000145:classification* / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000145:classification / Q000235:genetics; D006801:Humans; D002679:Pan troglodytes / Q000235:genetics*; D010802:Phylogeny; D012641:Selection, Genetic; D013045:Species Specificity
chemical_list: D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II