title: Evolutionary relationships of the classes of major histocompatibility complex genes.
abstract: A number of hypotheses have been proposed to account for the evolutionary origin of the classes of major histocompatibility complex (MHC) genes of vertebrates. According to one hypothesis the class II MHC evolved first, whereas another hypothesis holds that the class I MHC originated first as a result of a recombination between an immunoglobulin-like C-domain and the peptide-binding domain of an HSP70 heat-shock protein. A phylogenetic tree of C-domains from MHC and related molecules supports a relationship between the class II MHC alpha chain and beta 2-microglobulin and between the class II MHC beta-chain and the class I alpha chain. If this phylogeny is correct, the hypothesis that the class I MHC evolved by recombination with HSP70 is less parsimonious than the hypothesis that class II evolved first. Furthermore, when MHC peptide-binding domains are simultaneously aligned with HSP70 domains and with V-domains from members of the immunoglobulin superfamily, they are slightly more similar to the latter than to the former; and the class II alpha 1 and beta 1 domains show much greater similarity to each other than would be expected if they evolved from separate HSP70 domains. Thus, most evidence supports the hypothesis that the ancestral MHC molecule had a class II-like structure.
authors.affiliation: Department of Biology, Pennsylvania State University, University Park 16802.
authors.forename: A L
authors.initials: AL
authors.lastname: Hughes
authors.forename: M
authors.initials: M
authors.lastname: Nei
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites; D005805:Genes, MHC Class I / Q000235:genetics*; D005802:Genes, MHC Class II / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000737:chemistry; D006801:Humans; D010802:Phylogeny
chemical_list: D015703:Antigens, CD; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II