Comparative analysis of evolutionary modes in Mc1r coat color gene in wild mice and mustelids.

Sequences from ten species of Mus (Rodentia, Muridae) of the melanocortin-1 receptor (Mc1r) gene (945 bp), which plays a key role in coat color determination, were compared with an existing Mc1r dataset (ca. 498 bp) from 12 species of Mustela and Martes (Carnivora, Mustelidae). The dN/dS ratio (omega) was estimated at 0.19 for Mus and 0.35 for the mustelids, using a likelihood-based one-ratio model with empirical codon frequencies. Running the model with equal codon frequencies gave a dramatic increase in omega for the mustelids (1.02) but not for Mus (0.31), indicating stronger codon usage bias in Mc1r among mustelids. When omega was estimated with the free-ratio model, significantly accelerated rates of amino acid replacement (nearly 1 in omega) were seen in several regions of the Mus phylogeny, such as in the ancestral subgeneric lineages, possibly associated with ecological niche shifting. Our results suggest that both functional constraints on coat color variation and selective constraints on codon usage bias have participated in structuring Mc1r gene sequences. Furthermore, they suggest that these contrasting influences have acted differentially in Mus and the mustelid lineages, and also differentially during the course of evolution within the genus Mus.