Sex Determination in Mammals. How Many Genes are Involved?1

Abstract

The genetic mechanisms of sex determination in mammals have not yet been clarified. Y-linked and X-linked zinc finger genes from humans and mice were recently cloned and characterized. The Y-linked zinc finger gene was originally thought to be the testis-determining factor. However, at the present time, it seems clear that this gene is not the master gene triggering the cascade of events leading to sex determination. The human testis-determining factor gene is known to be located in the nonhomologous region of the short arm of the Y chromosome, close to an Alu repeat that marks the boundary of the pseudoautosomal region. Lately, this region has been found to contain a new gene that is a strong candidate for the male-determining factor. Data on humans and on laboratory and vole mice showing abnormalities of the sex determination mechanisms indicate that testis development depends on the presence of a testis-determining factor gene functioning in cooperation with X-linked and autosomal genes. Ovary development would depend on the absence of the testis-determining factor and perhaps on an alternative splicing of the transcripts from autosomal and X-linked genes involved in sex determination.