Where do phosphosites come from and where do they go after gene duplication?

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Biochemistry

Background:

• Gene duplication followed by divergence is a key mechanism for molecular innovation.
• Regulatory divergence, particularly at the transcriptional level, is well-studied, but posttranslational modification (PTM) divergence is less understood.
• Protein phosphorylation is a critical PTM influencing gene retention after duplication.

Purpose of the Study:

• To investigate if changes in phosphorylated amino acids (phosphosites) after gene duplication contribute to the regulatory divergence of paralogous proteins.
• To determine if the loss of phosphosites in one paralog can alter protein regulation.

Main Methods:

• Analysis of amino acid transitions following gene duplication events.
• Examination of phosphosite gains and losses in paralogous genes.
• Statistical analysis of amino acid substitutions, focusing on phosphorylated serine and threonine residues.

Main Results:

• Loss of phosphosites in one paralog is significantly biased towards substitutions with negatively charged amino acids.
• These substitutions can constitutively mimic the phosphorylated state, suggesting a regulatory divergence mechanism.
• Favored phosphomimetic transitions often require more than single mutational steps, implying complete phosphosite function loss before substitution.

Conclusions:

• Divergence between paralogs can arise from the loss of posttranslational regulatory control, not necessarily the loss of function itself.
• Gene duplication may facilitate transitions between phosphorylated and phosphomimetic amino acid states.
• Understanding PTM divergence is crucial for comprehending molecular evolution and innovation.