RAPID-SEQUENCE EVOLUTION OF THE MAMMALIAN SEX-DETERMINING GENE SRY

IN mammals, induction of male sex determination requires the Y-chromos ome gene SRY1. SRY encodes a protein with a central 'high mobility gro up' domain (HMG box) of about 78 amino acids1-3 . HMG boxes are found in a wide variety of proteins that bind to DNA with high affinity but differing degrees of sequence specificity4. The human SRY protein bind s to linear DNA with sequence specificity5 and to cruciform DNA struct ures without sequence specificity6. The DNA-binding activity of the SR Y protein resides in the HMG box and mutations in this region are asso ciated with sex reversal in XY females6-8. No function has been ascrib ed to the portions of the SRY protein outside the HMG box. SRY belongs to a family of genes that are related by sequence homology within the DNA-binding domain: the genes most similar to SRY (>60%) have been na med SOX genes (SRY box genes). None of the known SOX genes is homologo us to SRY outside the HMG-box region. Although SRY is an important dev elopmental regulator, its sequence is poorly conserved between species apart from the HMG-box domain. Here we investigate the coding sequenc e of SR Y in primates and find that evolution has been rapid in the re gions flanking the conserved domain. The high degree of sequence diver gence and the frequency of non-synonymous mutations suggest either tha t the majority of the coding sequence has no functional significance o r that directional selection has occurred.