Functional roles for noise in genetic circuits

Abstract

The genetic circuits that regulate cellular functions are subject to stochastic fluctuations, or ‘noise’, in the levels of their components. Noise, far from just a nuisance, has begun to be appreciated for its essential role in key cellular activities. Noise functions in both microbial and eukaryotic cells, in multicellular development, and in evolution. It enables coordination of gene expression across large regulons, as well as probabilistic differentiation strategies that function across cell populations. At the longest timescales, noise may facilitate evolutionary transitions. Here we review examples and emerging principles that connect noise, the architecture of the gene circuits in which it is present, and the biological functions it enables. We further indicate some of the important challenges and opportunities going forward.

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Figure 1: Gene expression noise is ubiquitous, and affects diverse systems at several levels.
Figure 2: Frequency modulation of stochastic nuclear localization bursts enables coordination of gene regulation.
Figure 3: Probabilistic differentiation.
Figure 4: Roles of noise in evolution.

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Acknowledgements

We thank G. Süel, A. Raj, F. Tan and J. Rossant for providing images. We thank N. Wingreen, D. J. Anderson, R. Kishony, J.-G. Ojalvo, G. Süel, H. Y. Kueh and members of the Elowitz laboratory for discussions. Work in M.B.E.’s laboratory was supported by NIH grants R01GM079771, P50 GM068763, NSF CAREER Award 0644463 and the Packard Foundation. A.E. was supported by EMBO, the International Human Frontier Science Organization and a Baxter fellowship.

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Correspondence to Michael B. Elowitz.

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Eldar, A., Elowitz, M. Functional roles for noise in genetic circuits. Nature 467, 167–173 (2010). https://doi.org/10.1038/nature09326

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