Gene expression noise facilitates adaptation and drug resistance independently of mutation

Phys Rev Lett. 2011 Nov 18;107(21):218101. doi: 10.1103/PhysRevLett.107.218101. Epub 2011 Nov 14.

Abstract

We show that the effect of stress on the reproductive fitness of noisy cell populations can be modeled as a first-passage time problem, and demonstrate that even relatively short-lived fluctuations in gene expression can ensure the long-term survival of a drug-resistant population. We examine how this effect contributes to the development of drug-resistant cancer cells, and demonstrate that permanent immunity can arise independently of mutations.

MeSH terms

  • Adaptation, Physiological / drug effects*
  • Adaptation, Physiological / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / genetics
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • Genetic Fitness / drug effects
  • Genetic Fitness / genetics
  • Models, Biological*
  • Mutation* / drug effects
  • Stress, Physiological / drug effects
  • Stress, Physiological / genetics
  • Time Factors