title: Ancestral polymorphism of Mhc class II genes in mice: implications for balancing selection and the mammalian molecular clock.
abstract: To investigate the evolutionary dynamics at Mhc class II DR genes of mice (genus Mus), we sequenced the peptide binding regions (PBRs) of 41 DRB (= E beta) genes and eight DRA (= E alpha) genes from 15 strains representing eight species. As expected trees of these PBR sequences imply extensive maintenance of ancestral DRB alleles across species. We use a coalescent simulation model to show that the number of interspecific coalescent events (c) observed on these trees was higher than the number expected for neutral genealogies and similar sample sizes and is more consistent with balancing selection that with neutrality. Patterns of ancestral polymorphism in mouse DRB alleles were also used to examine the tempo of synonymous substitution in the PBR of mouse class II genes. Both absolute and relative rate tests on DRA and DRB genes imply increased substitution rates at two- and fourfold degenerate sites of mice and rats relative to primates, and decreased rates for the DRB genes of primates relative to ungulate and carnivore relatives. Thus rates of synonymous substitution at Mhc DR genes in mammals appear to be subject to generation time effects in ways similar to those found at other mammalian genes.
authors.affiliation: Department of Zoology, University of Washington, Seattle 98195, USA. edwards@zoology.washington.edu
authors.forename: S V
authors.initials: SV
authors.lastname: Edwards
authors.forename: K
authors.initials: K
authors.lastname: Chesnut
authors.forename: Y
authors.initials: Y
authors.lastname: Satta
authors.forename: E K
authors.initials: EK
authors.lastname: Wakeland
mesh_terms: D000483:Alleles; D000818:Animals; D001665:Binding Sites; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005802:Genes, MHC Class II / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D012641:Selection, Genetic