The sex-determining region of the human Y chromosome encodes a finger protein.
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.
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142.
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Mosher
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Simpson
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Fisher
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Mardon
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Pollack
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McGillivray
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de la Chapelle
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Brown
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D005260:Female; D005796:Genes; D012739:Gonadal Steroid Hormones / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008297:Male; D008322:Mammals; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D012732:Sex Determination Analysis; D012733:Sex Differentiation; D014157:Transcription Factors; D014158:Transcription, Genetic; D014960:X Chromosome; D014998:Y Chromosome
D004268:DNA-Binding Proteins; D012739:Gonadal Steroid Hormones; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C054430:ZFY protein, human