Functional divergence and evolutionary turnover in mammalian phosphoproteomes

Area of Science:

• Evolutionary biology
• Molecular biology
• Biochemistry

Background:

• Protein phosphorylation regulates diverse cellular functions.
• Its role in species divergence, particularly in mammals, remains under-investigated.

Purpose of the Study:

• To investigate the evolutionary dynamics of protein phosphorylation in mammals.
• To compare human and mouse phosphoproteomes to understand species divergence.

Main Methods:

• Comparative phosphoproteomics of human and mouse.
• Analysis of conserved and differentially phosphorylated sites.
• Assessment of evolutionary turnover of phosphorylation sites.

Main Results:

• 84% of phosphorylation sites are conserved at the residue level between humans and mice.
• 20% of conserved sites are phosphorylated in both species, indicating purifying selection.
• A significant proportion of conserved sites show differential phosphorylation, with at least 5% likely representing true divergence.
• Evolutionary turnover of adjacent phosphosites can overestimate divergence but suggests functional redundancy.

Conclusions:

• Protein phosphorylation evolves through both conservation and divergence.
• Differential phosphorylation and turnover of sites contribute to species-specific phosphorylation networks and phenotypic evolution.
• This study provides a framework for analyzing phosphoproteome evolution and its link to phenotypic differences.