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Letters to Nature
Nature 336, 780 - 783 (29 December 1988); doi:10.1038/336780a0

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

Andrew H. Sinclair*, Jamie W. Foster, James A. Spencer, David C. Page, Mark Palmer, Peter N. Goodfellow & Jennifer A. Marshall Graves

Department of Genetics and Human Variation, La Trobe University, Bundoora, Victoria 3083, Australia
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Human Molecular Genetics Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, UK
*Present address: Human Molecular Genetics Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, UK.

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.

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