The origins and evolution of functional modules: lessons from protein complexes

Area of Science:

• Systems biology
• Evolutionary biology
• Structural biology

Background:

• Cellular systems display modularity, decomposable into cohesive, loosely coupled functional units.
• Protein complexes in physical protein interaction networks exemplify cellular modularity.
• Understanding the origin and evolution of protein complexes is crucial for systems biology.

Purpose of the Study:

• To investigate the emergence and evolution of protein complexes via gene duplication and other mechanisms.
• To analyze the structural properties of protein complexes and identify recurring patterns.
• To explore the evolutionary pressures on proteins within and across complexes.

Main Methods:

• Analysis of protein complex datasets with known three-dimensional structures.
• Dissection of protein-protein contacts within complexes.
• Comparative analysis of proteins shared across multiple complexes versus those in single complexes.

Main Results:

• Approximately 90% of analyzed protein complexes feature contacts between identical proteins.
• Proteins shared across different complexes are frequently essential genes.
• Gene duplication is a significant mechanism in the formation of new protein interactions and complexes.

Conclusions:

• Protein complex evolution is significantly shaped by duplication events and homomeric interactions.
• The essentiality of genes correlates with their involvement in multiple protein complexes.
• These findings offer insights into the growth of modularity in cellular networks, including transcriptional and metabolic networks.