Page D C, Mosher R, Simpson E M, Fisher E M, Mardon G, Pollack J, McGillivray B, de la Chapelle A, Brown L G
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142.
Cell. 1987 Dec 24;51(6):1091-104. doi: 10.1016/0092-8674(87)90595-2.
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.
Y染色体的存在与否决定了哺乳动物胚胎发育为雄性还是雌性。在人类中，对“性反转”个体的基因缺失分析已确定Y染色体的一小部分对于诱导双潜能性腺的睾丸分化是必要且充分的。我们报告了人类Y染色体一个230千碱基片段的克隆，该片段包含部分或全部睾丸决定因子基因（TDF），即主要的性别决定位点。克隆区域跨越了一名携带除160千碱基外所有Y染色体的女性的缺失区域。该区域内的某些DNA序列在进化过程中高度保守；在所检测的所有哺乳动物的Y染色体上均存在同源物。特别是，在小鼠Y染色体的性别决定区域内发现了同源序列。人类Y染色体上这种保守DNA的核苷酸序列表明它编码一种具有多个“指状”结构域的蛋白质，正如最初在蛙转录因子IIIA中所描述的那样。所编码的蛋白质可能以序列特异性方式与核酸结合，并可能调节转录。在人类和其他哺乳动物的X染色体上也存在非常相似的DNA序列。我们讨论了Y编码的指状蛋白是睾丸决定因子的可能性，并提出了性别决定模型，以适应在X染色体上发现相关位点这一情况。鸟类中类似序列的存在表明其不仅可能在哺乳动物的XX/XY性别决定系统中起作用，也可能在鸟类的ZZ/ZW系统中起作用。
