An SRY-related sequence on the marsupial X chromosome:implications for the evolution of the mammalian testis-determininggene.

The SRY gene on the human, mouse, and marsupial Ychromosomes is the testis-determining gene that initiates male development inmammals. The SRY protein has a DNA-binding domain (high mobility group or HMGbox) similar to those found in the high-mobility-group proteins. SRY is specificfor the Y chromosome, but many autosomal genes have been identified that possessa similar HMG box region; those with the most closely SRY-related box regionsform a gene family now referred to as SOX genes. We have identified a sequenceon the marsupial X chromosome that shares homology with SRY. Sequencecomparisons show near-identity with the mouse and human SOX3 gene (formerlycalled a3), the SOX gene which is the most closely related to SRY. We suggesthere that the highly conserved X chromosome-linked SOX3 represents the ancestralSOX gene from which the sex-determining gene SRY was derived. In this modelSOX3/SRY divergence and the acquisition of a testis-determining role by SRYmight have preceded (and initiated) sex chromosome differentiation or,alternatively, might have been a consequence of X chromosome-Y chromosomedifferentiation initiated at the locus of an original sex-determining gene(s),later superseded by SRY.