Systems biology: Network evolution hinges on history.

Abstract

The effects of mutations in proteins can depend on the occurrence of previous mutations. It emerges that such historical contingency is also important during the evolution of gene regulatory networks. See Letter p.361 Epistatic interactions — whereby a mutation's effect is contingent on another mutation — have been shown to constrain evolution within single proteins, but whether and how they may govern broader gene regulatory networks has remained largely hypothetical. Now Alexander Johnson and colleagues show that the appearance of Ste12 binding sites in the regulatory DNA of genes specific to the a mating type in the yeast Saccharomyces cerevisiae's pheromone response pathway has required the prior adoption of α2 repression in the mating-type pathway of its common ancestor with Kluyveromyces lactis. Thus historical contingency not apparent from scrutiny of individual regulatory factors — such as a single DNA-binding protein or a single transcriptional enhancer — can result from systems-level constraints on the evolution of regulatory pathways that share some of their components.