Editors' ChoiceSystems Biology

Why Cell Signaling Is Noisy

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Science Signaling  28 Sep 2010:
Vol. 3, Issue 141, pp. ec298
DOI: 10.1126/scisignal.3141ec298

Anyone who has made quantitative measurements of cellular events knows from experience that biochemical processes in cells show a substantial amount of variation or noise. Lestas et al. analyzed such noise—which is particularly prevalent when molecules are present in a low number of copies per cell—and the feedback control systems that keep variation in check and found that it is there not just because cells can’t be bothered to maintain tighter control. Rather, it is far too expensive for cells to exert such control to minimize noise. We are still too far from sufficiently complete characterization of cellular regulatory networks to allow detailed probabilistic models. However, a combination of control theory and information theory—like that used by engineers to model reliable systems for data communication—with analysis of stochastic kinetics that determine abundance of key molecules allowed the authors to uncover the exceptional cost of closely regulating such biochemical systems. For example, their modeling showed that it is not possible for a network to reduce noise in the abundance of a particular molecule whose production is regulated by feedback from a downstream signaling pathway unless the signaling molecules that provide feedback are produced more frequently than is the controlled component. Thus, reducing the standard deviation in abundance of a controlled component to one-tenth of its value requires production of the signaling component 10,000 times more frequently than that of the controlled component. Another key element is loss of information in cascades of signaling steps used in feedback control circuits. The authors’ analysis showed that changes to prevent propagation of noise exacerbated loss of information, and mechanisms that could minimize loss of information tended to amplify the noise. They therefore propose that variation in abundance of signaling components might not so much reflect a lack of precision but rather a minimization of information loss in the signaling cascade. These considerations also may put upper limits on the complexity of reaction networks that can practically function in cellular biochemical systems. Sun and Becskei provide commentary, complete with an analogy from Greek mythology.

I. Lestas, G. Vinnicombe, J. Paulsson, Fundamental limits on the suppression of molecular fluctuations. Nature 467, 174–178 (2010). [PubMed]

L. Sun, A. Becskei, The cost of feedback control. Nature 467, 163–164 (2010). [PubMed]

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