Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution

Nat Commun. 2012 Feb 21;3:682. doi: 10.1038/ncomms1687.

Abstract

During evolution, genetic networks are rewired through strengthening or weakening their interactions to develop new regulatory schemes. In the galactose network, the GAL1/GAL3 paralogues and the GAL2 gene enhance their own expression mediated by the Gal4p transcriptional activator. The wiring strength in these feedback loops is set by the number of Gal4p binding sites. Here we show using synthetic circuits that multiplying the binding sites increases the expression of a gene under the direct control of an activator, but this enhancement is not fed back in the circuit. The feedback loops are rather activated by genes that have frequent stochastic bursts and fast RNA decay rates. In this way, rapid adaptation to galactose can be triggered even by weakly expressed genes. Our results indicate that nonlinear stochastic transcriptional responses enable feedback loops to function autonomously, or contrary to what is dictated by the strength of interactions enclosing the circuit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Evolution, Molecular*
  • Galactokinase / genetics
  • Galactokinase / metabolism
  • Galactose / metabolism*
  • Gene Regulatory Networks*
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction*
  • Stochastic Processes
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*

Substances

  • DNA-Binding Proteins
  • GAL2 protein, S cerevisiae
  • GAL4 protein, S cerevisiae
  • Gal3 protein, S cerevisiae
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • GAL1 protein, S cerevisiae
  • Galactokinase
  • Galactose