Evolution of protein complexes by duplication of homomeric interactions

Background: Cellular functions are accomplished by the concerted actions of functional modules. The mechanisms driving the emergence and evolution of these modules are still unclear. Here we investigate the evolutionary origins of protein complexes, modules in physical protein-protein interaction networks. Results: We studied protein complexes in Saccharomyces cerevisiae, complexes of known three-dimensional structure in the Protein Data Bank and clusters of pairwise protein interactions in the networks of several organisms. We found that duplication of homomeric interactions, a large class of protein interactions, frequently results in the formation of complexes of paralogous proteins. This route is a common mechanism for the evolution of complexes and clusters of protein interactions. Our conclusions are further confirmed by theoretical modelling of network evolution. We propose reasons for why this is favourable in terms of structure and function of protein complexes. Conclusion: Our study provides the first insight into the evolution of functional modularity in protein-protein interaction networks, and the origins of a large class of protein complexes.