Evolution of testis-specific kinases TSSK1B and TSSK2 in primates.

Abstract

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. © 2012 American Society of Andrology and European Academy of Andrology.