Gene Expression Noise Facilitates Adaptation and Drug Resistance Independently of Mutation

TL;DR

This paper demonstrates that gene expression noise can enable long-term survival and drug resistance in cell populations without relying on genetic mutations, by modeling stress effects as a first-passage time problem.

Contribution

It introduces a novel model linking gene expression fluctuations to drug resistance and shows immunity can develop independently of mutations.

Findings

Short-lived gene expression fluctuations promote survival.

Gene expression noise contributes to drug resistance.

Immunity can arise without genetic mutations.

Abstract

We show that the effect of stress on the reproductive fitness of noisy cell populations can be modelled as first-passage time problem, and demonstrate that even relatively short-lived fluctuations in gene expression can ensure 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.