Ancestral polymorphism of Mhc class II genes in mice: Implications for balancing selection and the mammalian molecular clock

Scott V. Edwards, Kye Chesnut, Yoko Satta, Edward K. Wakeland

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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 (=Eβ) genes and eight DRA (=Eα) 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 of 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 than 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 rats for the DRB genes of primates relative to ungulate and carnivore relatives. Thus rates of synonymous substitution at Mhr DR genes in mammals appear to be subject to generation time effects in ways similar to those found at other mammalian genes.

Original languageEnglish (US)
Pages (from-to)655-668
Number of pages14
JournalGenetics
Volume146
Issue number2
StatePublished - Jun 1 1997

ASJC Scopus subject areas

  • Genetics

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