Whitfield L S, Lovell-Badge R, Goodfellow P N
Department of Genetics, Cambridge University, UK.
Nature. 1993 Aug 19;364(6439):713-5. doi: 10.1038/364713a0.
In mammals, induction of male sex determination requires the Y-chromosome gene SRY. SRY encodes a protein with a central 'high mobility group' domain (HMG box) of about 78 amino acids. HMG boxes are found in a wide variety of proteins that bind to DNA with high affinity but differing degrees of sequence specificity. The human SRY protein binds to linear DNA with sequence specificity and to cruciform DNA structures without sequence specificity. The DNA-binding activity of the SRY protein resides in the HMG box and mutations in this region are associated with sex reversal in XY females. No function has been ascribed to the portions of the SRY protein outside the HMG box. SRY belongs to a family of genes that are related by sequence homology within the DNA-binding domain: the genes most similar to SRY (> 60%) have been named SOX genes (SRY box genes). None of the known SOX genes is homologous to SRY outside the HMG-box region. Although SRY is an important developmental regulator, its sequence is poorly conserved between species apart from the HMG-box domain. Here we investigate the coding sequence of SRY in primates and find that evolution has been rapid in the regions flanking the conserved domain. The high degree of sequence divergence and the frequency of non-synonymous mutations suggest either that the majority of the coding sequence has no functional significance or that directional selection has occurred.
在哺乳动物中，雄性性别决定的诱导需要Y染色体基因SRY。SRY编码一种蛋白质，该蛋白质具有一个约78个氨基酸的中央“高迁移率族”结构域（HMG盒）。HMG盒存在于多种与DNA高亲和力结合但序列特异性程度不同的蛋白质中。人类SRY蛋白以序列特异性结合线性DNA，并以非序列特异性结合十字形DNA结构。SRY蛋白的DNA结合活性存在于HMG盒中，该区域的突变与XY女性的性反转有关。SRY蛋白HMG盒以外的部分尚未发现有任何功能。SRY属于一个在DNA结合域内通过序列同源性相关的基因家族：与SRY最相似（>60%）的基因被命名为SOX基因（SRY盒基因）。在HMG盒区域以外，已知的SOX基因没有一个与SRY同源。尽管SRY是一种重要的发育调节因子，但除了HMG盒结构域外，其序列在不同物种间的保守性很差。在这里，我们研究了灵长类动物中SRY的编码序列，发现保守结构域两侧区域的进化速度很快。高度的序列差异和非同义突变的频率表明，要么大部分编码序列没有功能意义，要么发生了定向选择。
