Selection on Network Dynamics Drives Differential Rates of Protein Domain Evolution
AffiliationUniv Arizona, Div Epidemiol & Biostat, Mel & Enid Zuckerman Coll Publ Hlth
Univ Arizona, Dept Mol & Cellular Biol
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationSelection on Network Dynamics Drives Differential Rates of Protein Domain Evolution 2016, 12 (7):e1006132 PLOS Genetics
Rights© 2016 Mannakee, Gutenkunst. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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AbstractThe long-held principle that functionally important proteins evolve slowly has recently been challenged by studies in mice and yeast showing that the severity of a protein knockout only weakly predicts that protein's rate of evolution. However, the relevance of these studies to evolutionary changes within proteins is unknown, because amino acid substitutions, unlike knockouts, often only slightly perturb protein activity. To quantify the phenotypic effect of small biochemical perturbations, we developed an approach to use computational systems biology models to measure the influence of individual reaction rate constants on network dynamics. We show that this dynamical influence is predictive of protein domain evolutionary rate within networks in vertebrates and yeast, even after controlling for expression level and breadth, network topology, and knockout effect. Thus, our results not only demonstrate the importance of protein domain function in determining evolutionary rate, but also the power of systems biology modeling to uncover unanticipated evolutionary forces.
NoteOpen Access Journal.
VersionFinal published version
SponsorsNational Science Foundation [DGE-1143953]; Achievement Rewards for College Scientists scholarship