Evolution of testis-specific kinases TSSK1B and TSSK2 in primates

Area of Science:

• Reproductive biology
• Evolutionary genetics
• Molecular biology

Background:

• Testis-specific serine/threonine protein kinases (TSSK1 and TSSK2) are crucial for male fertility in mice.
• Mouse Tssk1 and Tssk2 genes form a linked tandem, while human TSSK1 exists as a pseudogene (TSSK1A) and an intact gene (TSSK1B), with TSSK2 being intact.
• Understanding gene conservation between mice and humans is key for studying human infertility and developing male contraceptives.

Purpose of the Study:

• To analyze the evolutionary history of TSSK1 and TSSK2 genes in mammals, with a focus on primates.
• To investigate the functional impact of the K27R replacement mutation in human TSSK2.
• To explore potential differential functions between TSSK1B and TSSK2 in primates.

Main Methods:

• Comparative genomics analysis of TSSK1 and TSSK2 genes across mammalian species, particularly primates.
• Phylogenetic analysis to infer evolutionary selection pressures (negative and positive selection).
• Functional analysis of specific mutations, such as K27R in TSSK2.

Main Results:

• Kinase domains of primate TSSK1B and TSSK2 evolved under strong negative selection, indicating conserved essential functions.
• Positive selection was detected in the C-terminal domain of TSSK1B, suggesting evolving or specialized roles.
• The K27R mutation in TSSK2, common in humans, was functionally analyzed.

Conclusions:

• TSSK1B and TSSK2 kinase activity is conserved in primates, highlighting their importance in male reproduction.
• Evidence suggests that TSSK1B and TSSK2 may have diverged in function, particularly in their C-terminal regions.
• Evolutionary insights into TSSK genes provide a basis for understanding male infertility and developing targeted contraceptives.