Genetic evidence that ZFY is not the testis-determining factor

Abstract

In mammals, the testis determining gene (TDF), present on the Y chromosome, induces the undifferentiated gonads to form testes. The position of TDF on the human Y chromosome has been defined by analysing the genomes of XX males and XY females, generated by abnormal genetic exchange between the X and Y chromosomes in male meiosis. In this way TDF has been localized close to the pseudoautosomal region shared by the sex chromosomes, in the distal Y-specific region. A recently cloned human gene, ZFY, has many features indicating that it is TDF. For example, ZFY encodes a protein with many features of a transcription factor including a domain with multiple 'zinc-finger' motifs. Less consistent with ZFY being TDF, however, is the presence of a very similar gene, ZFX, on the X chromosome, and the presence of a sequence related to ZFY on autosomes in marsupials. We now report on analysis of XX males lacking ZFY. In these individuals, the male phenotype could be explained by a mutation in a gene 'downstream' of ZFY in the sex-determining hierarchy; but in that case there should be no exchange of material between the X and Y chromosomes. We find on the contrary that in 4 XX males lacking ZFY, there is exchange of Y-specific sequences next to the pseudoautosomal boundary, redefining the region in which TDF must lie.