RT Journal Article SR Electronic T1 Stochastic Gene Expression in a Single Cell JF Science JO Science FD American Association for the Advancement of Science SP 1183 OP 1186 DO 10.1126/science.1070919 VO 297 IS 5584 A1 Elowitz, Michael B. A1 Levine, Arnold J. A1 Siggia, Eric D. A1 Swain, Peter S. YR 2002 UL http://science.sciencemag.org/content/297/5584/1183.abstract AB 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.