RAPID EVOLUTION OF THE SEX-DETERMINING LOCUS IN OLD-WORLD MICE AND RATS

THE Y chromosome-linked sex determining locus (Sry) responsible for te stis determination in mammals1-5 contains a DNA-binding motif (HMG box ) that is conserved across species of marsupial and placental mammals (infraclasses Metatheria and Eutheria, respectively)1,4,6,7. But littl e to no sequence similarity is observed in flanking sequences between these two infraclasses, or among orders within each infraclass. We inv estigated the rate and pattern of evolution for the coding sequence of Sry in Old World mice and rats (subfamily Murinae). We found typical rates of synonymous substitution throughout the gene, but high rates o f non-synonymous substitution, especially in the C-terminal (non-HMG b ox) region, when compared to other genes8. This region is also charact erized by a frame-shift mutation and variation in a trinucleotide repe at motif. These data suggest that the non-box region is either functio nally unconstrained or has undergone species-specific adaptive diverge nce.