title: Interdependent MHC-DRB exon-plus-intron evolution in artiodactyls.
abstract: Exon 2 sequences of an expressed MHC-DRB locus from sheep were examined for polymorphisms in both the antigen-binding regions and the adjacent intronic mixed simple tandem repeat. Twenty-one novel exon 2 Ovar-DRB alleles were identified. Short nucleotide motifs are extensively shared between certain exon 2 regions of Ovar-DRB alleles. The simple repeat variations, the number of different amino acids at usually polymorphic sites, and the number of silent substitutions were reduced in the intraspecies analyses of sheep DRB sequences, compared with those of cattle and goats. It was paradoxical that the abundance of different sheep alleles was similar to that of cattle and goats. This paradox may be explained by postulating a relatively small number of "ancient" alleles, with the present-day Ovar-DRB alleles being generated by reciprocal exchange of nucleotide motifs. At the antigen-binding sites, new combinations of amino acids were maintained in Ovar-DRB alleles by strong positive selection. In sheep--and less pronounced in goats and cattle--the DRB alleles can be divided into two groups. In one group, silent substitutions are increased when compared with the other. This suggests separate evolutionary pathways for certain groups of DRB alleles within a species. The simple repetitive sequences are also discussed with respect to the evolution of DRB alleles.
authors.affiliation: Rhur University, Bochum, Germany.
authors.forename: F W
authors.initials: FW
authors.lastname: Schwaiger
authors.forename: E
authors.initials: E
authors.lastname: Weyers
authors.forename: J
authors.initials: J
authors.lastname: Buitkamp
authors.forename: A J
authors.initials: AJ
authors.lastname: Ede
authors.forename: A
authors.initials: A
authors.lastname: Crawford
authors.forename: J T
authors.initials: JT
authors.lastname: Epplen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001188:Artiodactyla / Q000235:genetics*; D002417:Cattle / Q000235:genetics; D005091:Exons; D005802:Genes, MHC Class II; D006041:Goats / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012756:Sheep / Q000235:genetics; D013045:Species Specificity
chemical_list: D000949:Histocompatibility Antigens Class II