Design of a MAPK signalling cascade balances energetic cost versus accuracy of information transmission

Nat Commun. 2020 Jul 13;11(1):3494. doi: 10.1038/s41467-020-17276-4.


Cellular processes are inherently noisy, and the selection for accurate responses in presence of noise has likely shaped signalling networks. Here, we investigate the trade-off between accuracy of information transmission and its energetic cost for a mitogen-activated protein kinase (MAPK) signalling cascade. Our analysis of the pheromone response pathway of budding yeast suggests that dose-dependent induction of the negative transcriptional feedbacks in this network maximizes the information per unit energetic cost, rather than the information transmission capacity itself. We further demonstrate that futile cycling of MAPK phosphorylation and dephosphorylation has a measurable effect on growth fitness, with energy dissipation within the signalling cascade thus likely being subject to evolutionary selection. Considering optimization of accuracy versus the energetic cost of information processing, a concept well established in physics and engineering, may thus offer a general framework to understand the regulatory design of cellular signalling systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GTPase-Activating Proteins / metabolism
  • Humans
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Protein Tyrosine Phosphatases / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomycetales / genetics
  • Saccharomycetales / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology


  • GTPase-Activating Proteins
  • SST2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Mitogen-Activated Protein Kinases
  • MSG5 protein, S cerevisiae
  • Protein Tyrosine Phosphatases