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Cited by 13Gene Regulatory Network AnalysisRNA and protein synthesis mechanismsBacterial Genetics and Biotechnology

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Noise robustness and metabolic load determine the principles of central dogma regulation

Open access
Lo, Teresa W., Choi, H. James, Huang, Dean, Wiggins, Paul A.·2024·Science Advances
DOI 10.1126/sciadv.ado3095PMC PMC11343026

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Abstract

The processes of gene expression are inherently stochastic, even for essential genes required for growth. How does the cell maximize fitness in light of noise? To answer this question, we build a mathematical model to explore the trade-off between metabolic load and growth robustness. The model provides insights for principles of central dogma regulation: Optimal protein expression levels for many genes are in vast overabundance. Essential genes are transcribed above a lower limit of one message per cell cycle. Gene expression is achieved by load balancing between transcription and translation. We present evidence that each of these regulatory principles is observed. These results reveal that robustness and metabolic load determine the global regulatory principles that govern gene expression processes, and these principles have broad implications for cellular function.

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Metadata

Authors
Lo, T. W., Choi, H. J., Huang, D., & Wiggins, P. A.
Affiliations
University of Washington (US)
Corresponding author
Wiggins, Paul A.
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2024-08-23
Volume
10
Issue
34
Pages
eado3095-eado3095
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.ado3095
PMC
PMC11343026
OpenAlex
W4401806214
Cited by
13
References
12
Citations by year
2026: 6 · 2025: 4 · 2024: 3
FWCI
1.75
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • arXiv (Cornell University) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • arXiv (Cornell University) (cc-by)
Funders
  • National Institutes of Health (5r01gm128191-03, R01-GM128191)
  • National Institute of General Medical Sciences (R01-GM128191)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
stochastic gene expression, metabolic burden, essential genes, protein abundance, mathematical model of gene regulation, fitness maximization

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