ANCESTRAL POLYMORPHISM OF MHC CLASS-II GENES IN MICE - IMPLICATIONS FOR BALANCING SELECTION AND THE MAMMALIAN MOLECULAR CLOCK

To investigate the evolutionary dynamics at Mhc class II DR genes of m ice (genus Mus),we sequenced the peptide binding regions (PBRs) of 41 DRB (=E beta) genes and eight DRA (=E alpha) genes from 15 strains rep resenting eight species. As expected trees of these PER sequences impl y extensive maintenance of ancestral DRB alleles across species. We us e a coalescent simulation model to show that the number of interspecif ic coalescent events (c) observed on these trees was higher than the n umber expected for neutral genealogies and similar sample sizes and is more consistent with balancing selection than with neutrality. Patter ns of ancestral polymorphism in mouse DRB alleles were also used to ex amine the tempo of synonymous substitution in the PER of mouse class I I genes. Both absolute and relative rate tests on DRA and DRB genes im ply increased substitution rates at two- and fourfold degnerate 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 a t other mammalian genes.