Stochastic Gene Expression in a Single Cell
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.
Additional Information© 2002 American Association for the Advancement of Science. Received 14 February 2002; accepted 13 June 2002. We thank U. Alon, S. Bekiranov, J. Dworkin, D. Endy, C. Guet, R. Kishony, S. Leibler, D. O'Carroll, N. Rajewsky, B. Shraiman, D. Thaler, and especially M. G. Surette for conversations and suggestions; A. Teresky and the Levine Lab for help; and J. Paulsson for his suggestion about the extrinsic noise profile. Recombination-proficient strains were provided by D. Court. Supported by the Burroughs-Wellcome Fund and the Seaver Institute (M.B.E.) and by NIH grant GM59018 (P.S.S.).
Supplemental Material - ElowitzSOM.pdf