title: Gene expression noise facilitates adaptation and drug resistance independently of mutation.
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.
authors.affiliation: Department of Physics, University of Ottawa, Ontario, Canada. daniel.charlebois@uottawa.ca
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Charlebois
authors.forename: Nezar
authors.initials: N
authors.lastname: Abdennur
authors.forename: Mads
authors.initials: M
authors.lastname: Kaern
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D056084:Genetic Fitness / Q000187:drug effects / Q000235:genetics; D008954:Models, Biological; D009154:Mutation / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D013997:Time Factors