Coherent feedforward transcriptional regulatory motifs enhance drug resistance

Phys Rev E Stat Nonlin Soft Matter Phys. 2014 May;89(5):052708. doi: 10.1103/PhysRevE.89.052708. Epub 2014 May 14.

Abstract

Fluctuations in gene expression give identical cells access to a spectrum of phenotypes that can serve as a transient, nongenetic basis for natural selection by temporarily increasing drug resistance. In this study, we demonstrate using mathematical modeling and simulation that certain gene regulatory network motifs, specifically coherent feedforward loop motifs, can facilitate the development of nongenetic resistance by increasing cell-to-cell variability and the time scale at which beneficial phenotypic states can be maintained. Our results highlight how regulatory network motifs enabling transient, nongenetic inheritance play an important role in defining reproductive fitness in adverse environments and provide a selective advantage subject to evolutionary pressure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological
  • Computer Simulation
  • Drug Resistance / physiology*
  • Feedback, Physiological
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Gene Regulatory Networks*
  • Genetic Fitness
  • Models, Biological*
  • Population Dynamics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology
  • Stochastic Processes