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What is Proteins with Greater Influence on Network Dynamics Evolve More Slowly but Are Not More Essential about?

A fundamental question for evolutionary biology is why rates of evolution vary dramatically between proteins. Perhaps surprisingly, it is controversial how much a protein's functional importance affects its rate of evolution. In most studies, functional importance has been measured on the coarse scale of protein knock-outs, while evolutionary rate has been measured on the fine scale of amino acid substitutions. Here we introduce dynamical influence, a finer measure of protein functional importance. To measure dynamical influence, we first use detailed biochemical models of particular reaction networks to measure the influence of each reaction rate constant on network dynamics. We then define the dynamical influence of a protein to be the average influence of the rate constants for all reactions it is involved in. Using models of a dozen biochemical systems and sequence data from vertebrates, we show that dynamical influence and evolutionary rate are negatively correlated; proteins with greater dynamical influence evolve more slowly. We also show that proteins with greater dynamical influence are not more likely to be essential. This suggests that there are many cellular reactions w

Author

Gutenkunst, Ryan N.

Published

2009

Language

EN