摘要
The testis-specific serine/threonine protein kinases TSSK1 and TSSK2 are known to be essential for male fertility, in mice. The enzymes are present in elongating spermatids, and targeted deletion of the two genes Tssk1 and Tssk2 results in dysregulation of spermiogenesis. The mouse genes are genetically closely linked, forming a Tssk1–Tssk2 tandem. In human, TSSK1 is present in the form of a pseudogene, TSSK1A, which is linked to an intact TSSK2 gene, and in the form of an intact gene, TSSK1B, which is not genetically linked to TSSK2. Studies on conservation of genes and gene function between mouse and human are relevant, to be able to use mouse models for studies on human infertility, and to evaluate possible targets for non-hormonal contraception targeting the male. Therefore, we have performed a detailed analysis of the evolution of genes encoding TSSK1 and TSSK2 among mammals, in particular among primates. This study includes functional analysis of replacement mutation K27R in TSSK2, which is frequently observed among humans. In primates, the kinase domains of TSSK1B and TSSK2 have evolved under negative selection, reflecting the importance to maintain their kinase activity. Positive selection was observed for the C-terminal domain of TSSK1B, which indicates that TSSK1B and TSSK2 may perform at least partly differential functions.
摘要译文
睾丸特异性丝氨酸/苏氨酸蛋白激酶TSSK1和TSSK2已知是对男性生育必不可少的，在小鼠。酶存在于长形精子，和有针对性的缺失两个基因Tssk1和Tssk2结果中精子的失调。鼠标基因遗传有着密切的联系，形成了Tssk1，Tssk2串联。在人类，TSSK1存在于假基因，TSSK1A，它链接到一个完整的TSSK2基因的形式，而在一个完整的基因，TSSK1B，这是不遗传连锁TSSK2的形式。研究保护小鼠和人之间的基因和基因功能是相关的，以便能够使用小鼠模型用于对人不育症研究，并评价可能的目标，非激素避孕针对男性。因此，我们已经完成基因编码TSSK1和TSSK2哺乳动物之间的进化进行了详细分析，特别是灵长类动物中。这项研究包括更换突变K27R在TSSK2，这是经常在人群中观察到的功能分析。在灵长类动物中，TSSK1B和TSSK2的激酶结构域已在负选择的演变，反映的重要性，以保持其激酶活性。阳性选择观察到TSSK1B的C-末端结构域，这表明TSSK1B和TSSK2可以执行至少部分地微分函数。
P. Shang, J. Hoogerbrugge, W. M. Baarends, J. A. Grootegoed[*]. Evolution of testis-specific kinases TSSK1B and TSSK2 in primates[J]. Andrology, 2013,1(1): 160-168