Abstract
Phenotype robustness to environmental fluctuations is a common biological phenomenon. Although most phenotypes are governed by multiple proteins that interact with each other, the basic principles of how such interactome networks respond to environmental unpredictability and change during evolution are largely unknown. Here we study interactomes of 1,840 species across the tree of life involving a total of 8,762,166 protein-protein interactions. Our study focuses on the resilience of interactomes to protein failures and finds that interactomes become more resilient during evolution, indicating that a species’ position in the tree of life is predictive of how robust its interactome is to protein failures. In bacteria, we find that a more resilient interactome is in turn associated with the greater ability of the organism to survive in a more complex, variable and competitive environment. We find that at the protein family level, proteins exhibit a coordinated rewiring of interactions over time and that a resilient interactome arises through gradual change of the network topology. Our findings have implications for understanding molecular network structure both in the context of evolution and environment.