Central dogma rates and the trade-off between precision and economy in gene expression
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Abstract
Steady-state protein abundance is set by four rates: transcription, translation, mRNA decay and protein decay. A given protein abundance can be obtained from infinitely many combinations of these rates. This raises the question of whether the natural rates for each gene result from historical accidents, or are there rules that give certain combinations a selective advantage? We address this question using high-throughput measurements in rapidly growing cells from diverse organisms to find that about half of the rate combinations do not exist: genes that combine high transcription with low translation are strongly depleted. This depletion is due to a trade-off between precision and economy: high transcription decreases stochastic fluctuations but increases transcription costs. Our theory quantitatively explains which rate combinations are missing, and predicts the curvature of the fitness function for each gene. It may guide the design of gene circuits with desired expression levels and noise.
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- Authors
- Hausser, J., Mayo, A., Keren, L., & Alon, U.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Hausser, Jean
- Alon, Uri
- Venue
- Nature Communications
- Published
- 2019-01-08
- Volume
- 10
- Issue
- 1
- Pages
- 68-68
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6325141
- OpenAlex
- W2909620196
- Cited by
- 188
- References
- 16
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 36 · 2023: 30 · 2022: 23 · 2021: 20 · 2020: 27 · 2019: 16
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Science Foundation
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (158472)
- Israel Science Foundation
- FP7 Ideas: European Research Council (249919)
- 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 › Evolution and Genetic Dynamics
- Keywords
- gene expression regulation, transcription, translation (biology), mRNA degradation, gene circuit design
- MeSH terms
- Animals, Escherichia coli, Gene Expression Regulation, Humans, Models, Genetic, RNA, Messenger, Saccharomyces cerevisiae, Transcription, Genetic, Protein Biosynthesis, Genome, Computational Biology, RNA Stability, Mice, Gene Regulatory Networks, Genetic Fitness, High-Throughput Screening Assays, Datasets as Topic
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