Biological role of noise encoded in a genetic network motif

Biological role of noise encoded in a genetic network motif
Mark Kittisopikul and Gürol M. Süel1
+ Author Affiliations

Green Center for Systems Biology and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390
Edited* by José N. Onuchic, University of California at San Diego, La Jolla, CA, and approved June 4, 2010 (received for review March 25, 2010)

Abstract
Genetic circuits that regulate distinct cellular processes can differ in their wiring pattern of interactions (architecture) and susceptibility to stochastic fluctuations (noise). Whether the link between circuit architecture and noise is of biological importance remains, however, poorly understood. To investigate this problem, we performed a computational study of gene expression noise for all possible circuit architectures of feed-forward loop (FFL) motifs. Results revealed that FFL architectures fall into two categories depending on whether their ON (stimulated) or OFF (unstimulated) steady states exhibit noise. To explore the biological importance of this difference in noise behavior, we analyzed 858 documented FFLs in Escherichia coli that were divided into 39 functional categories. The majority of FFLs were found to regulate two subsets of functional categories. Interestingly, these two functional categories associated with FFLs of opposite noise behaviors. This opposite noise preference revealed two noise-based strategies to cope with environmental constraints where cellular responses are either initiated or terminated stochastically to allow probabilistic sampling of alternative states. FFLs may thus be selected for their architecture-dependent noise behavior, revealing a biological role for noise that is encoded in gene circuit architectures.

gene expression bursts stochastic simulation design principles demand theory shot noise
Footnotes
1To whom correspondence should be addressed. E-mail: Gurol.Suel@UTSouthwestern.edu. Author contributions: M.K. and G.M.S. designed research; M.K. performed research; M.K. and G.M.S. analyzed data; and M.K. and G.M.S. wrote the paper.
The authors declare no conflict of interest.
*This Direct Submission article had a prearranged editor.
See Commentary on page 13197.
This article contains supporting information online at
www.pnas.org/lookup/suppl/doi:10.1073/pnas.1003975107/-/DCSupplemental.

http://www.pnas.org/content/107/30/13300