DOI: 10.1073/pnas.151588598. Intrinsic noise in gene regulatory networks

Intrinsic noise in gene regulatory networks

10.1073/pnas.151588598

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Cells are intrinsically noisy biochemical reactors: low reactant numbers can lead to significant statistical fluctuations in molecule numbers and reaction rates. Here we use an analytic model to investigate the emergent noise properties of genetic systems. We find for a single gene that noise is essentially determined at the translational level, and that the mean and variance of protein concentration can be independently controlled. The noise strength immediately following single gene induction is almost twice the final steady-state value. We find that fluctuations in the concentrations of a regulatory protein can propagate through a genetic cascade; translational noise control could explain the inefficient translation rates observed for genes encoding such regulatory proteins. For an autoregulatory protein, we demonstrate that negative feedback efficiently decreases system noise. The model can be used to predict the noise characteristics of networks of arbitrary connectivity. The general procedure is further illustrated for an autocatalytic protein and a bistable genetic switch. The analysis of intrinsic noise reveals biological roles of gene network structures and can lead to a deeper understanding of their evolutionary origin.

Bibliography

Thattai, M., & van Oudenaarden, A. (2001). Intrinsic noise in gene regulatory networks. Proceedings of the National Academy of Sciences, 98(15), 8614â8619.

Authors 2

Mukund Thattai (first)
Alexander van Oudenaarden (additional)

References 29 Referenced 1,234

10.1016/S0168-9525(98)01659-X
10.1093/genetics/149.4.1633
10.1016/0168-9525(92)90331-W
10.1038/35018085
10.1016/S0022-5193(05)80421-7
10.1073/pnas.95.26.15641
10.1016/S0006-3495(00)76531-3
10.1006/tpbi.1995.1027
10.1016/0022-5193(78)90326-0
10.1126/science.283.5400.381
10.1073/pnas.040411297
10.1073/pnas.94.3.814
10.1016/0022-2836(77)90279-0
10.1038/35014651
10.1073/pnas.94.15.8168
10.1006/jtbi.1999.1010
10.1038/35002131
10.1038/35002125
10.1002/j.1460-2075.1982.tb01176.x
10.1073/pnas.110057697
10.1103/PhysRevLett.84.5447
10.1128/JB.180.12.3019-3025.1998
10.1042/bj3060123
10.1146/annurev.bi.54.070185.001131
10.1006/jmbi.1994.0028
10.1016/0022-2836(85)90086-5
10.1016/0022-2836(92)90617-S
N G van Kampen Stochastic Processes in Physics and Chemistry (North–Holland, Amsterdam, 1992). / Stochastic Processes in Physics and Chemistry by van Kampen N G (1992)
10.1021/j100540a008

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:34 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 11:53 p.m.)
Indexed	3 days, 3 hours ago (Sept. 3, 2025, 6:30 a.m.)
Issued	24 years, 2 months ago (July 3, 2001)
Published	24 years, 2 months ago (July 3, 2001)
Published Online	24 years, 2 months ago (July 3, 2001)
Published Print	24 years, 1 month ago (July 17, 2001)

Funders 0

None

BibTeX

@article{Thattai_2001, title={Intrinsic noise in gene regulatory networks}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.151588598}, DOI={10.1073/pnas.151588598}, number={15}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Thattai, Mukund and van Oudenaarden, Alexander}, year={2001}, month=jul, pages={8614–8619} }

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