Evolutionary fate of duplicate genes encoding aspartic proteinases. Nothepsin case study

Area of Science:

• Evolutionary biology
• Molecular evolution
• Genetics

Background:

• Gene duplication is a key evolutionary mechanism for acquiring new gene functions.
• The classical model posits that paralogs persist only through neofunctionalization, with loss occurring otherwise.
• Recent research suggests alternative mechanisms for paralog maintenance without neofunctionalization.

Purpose of the Study:

• To investigate the molecular evolution of the aspartic proteinase gene family, focusing on the nothepsin gene.
• To understand the evolutionary trajectory and potential loss of nothepsin across different vertebrate lineages.
• To elucidate the mechanisms maintaining paralogous genes like nothepsin and cathepsin D.

Main Methods:

• Comparative analysis of gene duplication events and functional divergence.
• Phylogenetic analysis to assess evolutionary pressures (negative selection, amino acid substitutions).
• Examination of gene expression patterns (tissue-specific, sex-specific, constitutive) in fish and reptiles.

Main Results:

• Nothepsin, an aspartic proteinase, is found in fish and reptiles but lost in avian, murine, and human genomes.
• Piscine nothepsin is sex- and tissue-specific, while reptilian nothepsin is constitutively expressed.
• Functional divergence analysis shows cathepsin D accumulated substitutions, while nothepsin retained ancestral functions, evolving under negative selection.

Conclusions:

• A model is proposed where complementary mutations in regulatory elements lead to gene loss when paralogs acquire identical expression patterns.
• The coexistence of cathepsin D and nothepsin is potentially explained by metabolic cooperation.
• Gene loss of nothepsin in certain lineages highlights the dynamic nature of evolutionary pathways beyond simple neofunctionalization.