Faculty Research 1980 - 1989

Title

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

Document Type

Article

Publication Date

1987

Keywords

Animal, Base-Sequence, Cloning-Molecular, Evolution, Female, Genes, Human, Male, Mammals, Molecular-Sequence-Data, Sequence-Homology-Nucleic-Acid, Sex-Determination, Sex-Differentiation, Sex-Hormones: ge, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Transcription-Genetic, X-Chromosome, Y-Chromosome

JAX Source

Cell 1987 Dec 24;51(6):1091-104

Grant

TWO3951

Abstract

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 XX/XY sex determination system of mammals, but also in the ZZ/ZW system of birds.

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