title: Ancestral major histocompatibility complex DRB genes beget conserved patterns of localized polymorphisms.
abstract: Genes within the major histocompatibility complex (MHC) are characterized by extensive polymorphism within species and also by a remarkable conservation of contemporary human allelic sequences in evolutionarily distant primates. Mechanisms proposed to account for strict nucleotide conservation in the context of highly variable genes include the suggestion that intergenic exchange generates repeated sets of MHC DRB polymorphisms [Gyllensten, U. B., Sundvall, M. & Erlich, H. A. (1991) Proc. Natl. Acad. Sci. USA 88, 3686-3690; Lundberg, A. S. & McDevitt, H. 0. (1992) Proc. Natl. Acad. Sci. USA 89, 6545-6549]. We analyzed over 50 primate MHC DRB sequences, and identified nucleotide elements within macaque and baboon DRB6-like sequences with deletions corresponding to specific exon 2 hypervariable regions, which encode a discrete alpha helical segment of the MHC antigen combining site. This precisely localized deletion provides direct evidence implicating segmental exchange of MHC-encoded DRB gene fragments as one of the evolutionary mechanisms both generating and maintaining MHC diversity. Intergenic exchange at this site may be fundamental to the diversification of immune protection in populations by permitting alteration in the specificity of the MHC that determines the repertoire of antigens bound.
authors.affiliation: Puget Sound Blood Center, Seattle, WA 98104-1256, USA.
authors.forename: L K
authors.initials: LK
authors.lastname: Gaur
authors.forename: G T
authors.initials: GT
authors.lastname: Nepom
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D017124:Conserved Sequence; D017931:DNA Primers; D005091:Exons; D005701:Galago; D014644:Genetic Variation; D006684:HLA-DR Antigens / Q000235:genetics*; D059806:HLA-DR beta-Chains; D059811:HLA-DRB1 Chains; D006801:Humans; D007900:Lemur; D008251:Macaca; D008969:Molecular Sequence Data; D010215:Papio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011323:Primates; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid
chemical_list: D017931:DNA Primers; D006684:HLA-DR Antigens; D059806:HLA-DR beta-Chains; D059811:HLA-DRB1 Chains; C069699:HLA-DRB6 antigen