Stochastic Gene Expression in a Single Cell

TLDR

Clonal populations of cells exhibit substantial phenotypic variation, which can be essential for many biological processes and is conjectured to arise from stochasticity, or noise, in gene expression. The study constructed Escherichia coli strains to detect noise and discriminate between intrinsic and extrinsic mechanisms of gene expression. Using engineered E. coli, the authors quantified intrinsic and extrinsic noise, showing that transcription rate, regulatory dynamics, and genetic factors control noise amplitude.

Abstract

Clonal populations of cells exhibit substantial phenotypic variation. Such heterogeneity can be essential for many biological processes and is conjectured to arise from stochasticity, or noise, in gene expression. We constructed strains of Escherichia coli that enable detection of noise and discrimination between the two mechanisms by which it is generated. Both stochasticity inherent in the biochemical process of gene expression (intrinsic noise) and fluctuations in other cellular components (extrinsic noise) contribute substantially to overall variation. Transcription rate, regulatory dynamics, and genetic factors control the amplitude of noise. These results establish a quantitative foundation for modeling noise in genetic networks and reveal how low intracellular copy numbers of molecules can fundamentally limit the precision of gene regulation.