Microsatellite-encoded domain in rodent Sry functions as a genetic capacitor to enable the rapid evolution of biological novelty

Gene duplication is prominent among evolutionary pathways through which novel transcription factors and gene regulatory networks evolve. A model in mammals is provided by Sry, a Y-encoded Sox factor that initiates male development. We provide evidence that a CAG DNA microsatellite invasion into the Sry gene of a rodent superfamily enabled its rapid evolution. This unstable microsatellite encodes a variable length glutamine-rich repeat domain. Our results suggest that intragenic complementation between the glutamine-rich domain and canonical Sry motifs accelerated their divergence through repeat length-dependent biochemical linkages. Such novelty may underlie emergence of non-Sry-dependent mechanisms of male sex determination.