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Science 296 (5568): 750-752

Copyright © 2002 by the American Association for the Advancement of Science

Evolutionary Rate in the Protein Interaction Network

Hunter B. Fraser,1*dagger Aaron E. Hirsh,2* Lars M. Steinmetz,3 Curt Scharfe,3 Marcus W. Feldman2

High-throughput screens have begun to reveal the protein interaction network that underpins most cellular functions in the yeast Saccharomyces cerevisiae. How the organization of this network affects the evolution of the proteins that compose it is a fundamental question in molecular evolution. We show that the connectivity of well-conserved proteins in the network is negatively correlated with their rate of evolution. Proteins with more interactors evolve more slowly not because they are more important to the organism, but because a greater proportion of the protein is directly involved in its function. At sites important for interaction between proteins, evolutionary changes may occur largely by coevolution, in which substitutions in one protein result in selection pressure for reciprocal changes in interacting partners. We confirm one predicted outcome of this process--namely, that interacting proteins evolve at similar rates.

1 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
2 Center for Computational Genetics and Biological Modeling, Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
3 Stanford Genome Technology Center, Palo Alto, CA 94306, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: hunter{at}

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