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

Abstract

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 phenotype. Recently, a candidate for the testis-determining gene (ZFY, Y-borne zinc-finger protein) has been cloned. 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 chromosome. In marsupials it is also the Y chromosome that seems to determine the fate of the gonad, but not all sexual dimorphisms. 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 autosomes. 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.

Chromosomal localization of ZFX—A human gene that escapes X inactivation—and its murine homologs

“…Specifically, it appears that a segment spanning the DMD and ZFX genes has remained grossly intact during the divergence of the human and mouse X chromosomes (Mitchell et al, 1989). Indeed, in marsupials, homologs of DMD and ZFX/ZFY map in proximity, but on an autosome (Sinclair et al, 1988). Thus, the DMD-ZFX linkage may predate the divergence of placental mammals and marsupials which occurred at least 130 million years ago (Air et al, 1971).…”

Immune Deficiency in CHARGE Association

“…In marsupials, sequences homologous to the ZFY map to autosomes. 21 Although their function has not been fully delineated yet, the encoded protein of ZFY binds to nucleic acids in a sequencespecific manner to regulate transcription. The development of CHARGE association in Kushnick's patient may be the result of dysregulation in the transcription process rather than a Y chromosome defect.…”

Genes envolvidos na determinação e diferenciação do sexo

“…A busca por esse "gene" durou cerca de 30 anos e sua descoberta mostrou que os mecanismos genéti-cos da determinação sexual são ainda mais complexos do que se imaginava (13)(14)(15)(16).…”