Evolutionary Rate in the Protein Interaction Network
Hunter B. Fraser,1*
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.
To whom correspondence should be addressed. E-mail:
hunter{at}ocf.berkeley.edu
