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Engineering stochasticity in gene expression

Tabor, Jeffrey J. and Bayer, Travis S. and Simpson, Zachary B. and Levy, Matthew and Ellington, Andrew D. (2008) Engineering stochasticity in gene expression. Molecular BioSystems, 4 (7). pp. 754-761. ISSN 1742-206X. doi:10.1039/b801245h.

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Stochastic fluctuations (noise) in gene expression can cause members of otherwise genetically identical populations to display drastically different phenotypes. An understanding of the sources of noise and the strategies cells employ to function reliably despite noise is proving to be increasingly important in describing the behavior of natural organisms and will be essential for the engineering of synthetic biological systems. Here we describe the design of synthetic constructs, termed ribosome competing RNAs (rcRNAs), as a means to rationally perturb noise in cellular gene expression. We find that noise in gene expression increases in a manner proportional to the ability of an rcRNA to compete for the cellular ribosome pool. We then demonstrate that operons significantly buffer noise between coexpressed genes in a natural cellular background and can even reduce the level of rcRNA enhanced noise. These results demonstrate that synthetic genetic constructs can significantly affect the noise profile of a living cell and, importantly, that operons are a facile genetic strategy for buffering against noise.

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Additional Information:This journal is © The Royal Society of Chemistry 2008. Received 23rd January 2008, Accepted 11th March 2008. First published on the web 1st May 2008. We thank K. E. Griswold for assistance with two-channel flow cytometry, E. A. Davidson for the GFP expression plasmid, J. J. Bull, J. J. Collins, E. M. Marcotte and C. A. Voigt for critical reading of an earlier version of the manuscript. We also thank several anonymous reviewers for insightful commentary and suggestions. This work was supported by NIH grant #9R01GM077040-05, the Welch Foundation and the Texas Higher Education Coordinating Board TDT-003658-0611-2003. Electronic supplementary information (ESI) available: Supplementary Table 1 and details on reporter independence. See DOI: 10.1039/b801245h
Funding AgencyGrant Number
National Institutes of Health9R01GM077040-05
Welch FoundationUNSPECIFIED
Texas Higher Education Coordinating BoardTDT-003658-0611-2003
Issue or Number:7
Record Number:CaltechAUTHORS:TABmbs08
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11179
Deposited By: Archive Administrator
Deposited On:22 Jul 2008 04:29
Last Modified:08 Nov 2021 21:33

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