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.
Elowitz
Michael B
MB
Laboratory of Cancer Biology, Center for Studies in Physics and Biology, Rockefeller University, New York, NY 10021, USA. elowitm@rockefeller.edu
Levine
Arnold J
AJ
Siggia
Eric D
ED
Swain
Peter S
PS
D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics*; D003470:Culture Media; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins; D005453:Fluorescence; D018628:Gene Dosage; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D007091:Image Processing, Computer-Assisted; D007544:Isopropyl Thiogalactoside / Q000378:metabolism / Q000494:pharmacology; D056968:Lac Repressors; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D013269:Stochastic Processes; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D003470:Culture Media; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D008164:Luminescent Proteins; D012097:Repressor Proteins; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins; D007544:Isopropyl Thiogalactoside