Sequences homologous to ZFY, a candidate human sex-determining gene, are autosomal in marsupials

Sexual differentiation in placental mammals results from the action of a testis-determining gene encoded by the Y chromosome. This gene causes the indifferent gonad to develop as a testis, thereby initiating a hormonal cascade which produces a male phenotype1,2. Recently, a candidate for the testis-determining gene (ZFY, Y-borne zinc-finger protein) has been cloned3,4. The ZFY probe detects a male-specific (Y-linked) sequence in DNA from a range of eutherian mammals, as well as an X-linked sequence (ZFX) which maps to the human X chromosome3. In marsupials it is also the Y chromosome that seems to determine the fate of the gonad, but not all sexual dimorphisms5. Using the ZFY probe we find, surprisingly, that the ZFY homologous sequences are not on either the X or the Y chromosome in marsupials, but map to the auto-somes. This implies ZFY is not the primary sex-determining gene in marsupials. Either the genetic pathways of sex determination in marsupials and eutherians differ, or they are identical and ZFY is not the primary signal in human sex determination.