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Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4426-4433. doi: 10.1073/pnas.1818013116. Epub 2019 Feb 14.

Evolution of resilience in protein interactomes across the tree of life.

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Department of Computer Science, Stanford University, Stanford, CA 94305.
Department of Biology, Stanford University, Stanford, CA 94305;
Department of Computer Science, Stanford University, Stanford, CA 94305;
Chan Zuckerberg Biohub, San Francisco, CA 94158.


Phenotype robustness to environmental fluctuations is a common biological phenomenon. Although most phenotypes involve 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 network failures and finds that interactomes become more resilient during evolution, meaning that interactomes become more robust to network failures over time. 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 in the context of both evolution and environment.


ecology; molecular evolution; network resilience; network rewiring; proteinprotein interaction networks

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