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The sex-determining region of the human Y chromosome encodes a finger protein

1987; Cell Press; Volume: 51; Issue: 6 Linguagem: Inglês

10.1016/0092-8674(87)90595-2

1097-4172

David C. Page, Rebecca A. Mosher, Elizabeth M. Simpson, Elizabeth Fisher, Graeme Mardon, Jonathan R. Pollack, Barbara McGillivray, Albert de la Chapelle, Laura G. Brown,

Sexual Differentiation and Disorders

The presence or absence of the Y chromosome determines whether a mammalian embryo develops as a male or female. In humans, genetic deletion analysis of “sex-reversed” individuals has identified a small portion of the Y chromosome necessary and sufficient to induce testicular differentiation of the bipotential gonad. We report the cloning of a 230-kilobase segment of the human Y chromosome that contains some or all of the testis-determining factor gene (TDF), the master sex-determining locus. The cloned region spans the deletion in a female who carries all but 160 kilobases of the Y. Certain DNA sequences within this region were highly conserved during evolution; homologs occur on the Y chromosomes of all mammals examined. In particular, homologous sequences are found within the sex-determining region of the mouse Y chromosome. The nucleotide sequence of this conserved DNA on the human Y chromosome suggests that it encodes a protein with multiple “finger” domains, as first described in frog transcription factor IIIA. The encoded protein probably binds to nucleic acids in a sequence-specific manner, and may regulate transcription. Very similar DNA sequences occur on the X chromosome of humans and other mammals. We discuss the possibility that the Y-encoded finger protein is the testis-determining factor, and propose models of sex determination accommodating the finding of a related locus on the X chromosome. The presence of similar sequences in birds suggests a possible role not only in the sex determination system of mammals, but also in the system of birds.