Mechanisms of noise-resistance in genetic oscillators.
Open accessAbstract
A wide range of organisms use circadian clocks to keep internal sense of daily time and regulate their behavior accordingly. Most of these clocks use intracellular genetic networks based on positive and negative regulatory elements. The integration of these “circuits” at the cellular level imposes strong constraints on their functioning and design. Here, we study a recently proposed model [Barkai, N. & Leibler, S. (2000) Nature (London) , 403, 267–268] that incorporates just the essential elements found experimentally. We show that this type of oscillator is driven mainly by two elements: the concentration of a repressor protein and the dynamics of an activator protein forming an inactive complex with the repressor. Thus, the clock does not need to rely on mRNA dynamics to oscillate, which makes it especially resistant to fluctuations. Oscillations can be present even when the time average of the number of mRNA molecules goes below one. Under some conditions, this oscillator is not only resistant to but, paradoxically, also enhanced by the intrinsic biochemical noise.
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By examining 17 models from the systems biology literature, the paper showed that their parameter sensitivities all share striking common features deemed "sloppiness".
“By examining 17 models from the systems biology literature [2,21,25,28–41], we showed that their parameter sensitivities all share striking common features deemed “sloppiness””
From Universally Sloppy Parameter Sensitivities in Systems Biology Models (2007) · cites this paper as [31]
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- Authors
- Vilar, J. M. G., Kueh, H. Y., Barkai, N., & Leibler, S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-04-23
- Volume
- 99
- Issue
- 9
- Pages
- 5988-5992
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC122889
- OpenAlex
- W2108493072
- Cited by
- 595
- References
- 0
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 7 · 2022: 13 · 2021: 24 · 2020: 21 · 2019: 11 · 2018: 19 · 2017: 15 · 2016: 23 · 2015: 27 · 2014: 32 · 2013: 26 · 2012: 29
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- arXiv (Cornell University)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
- Keywords
- circadian clock, genetic oscillators, noise robustness, biochemical noise, mRNA dynamics, stochastic gene expression, positive and negative feedback
- MeSH terms
- Algorithms, Circadian Rhythm, Models, Genetic, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Time Factors, Transcription, Genetic, Models, Statistical
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