Effects of DNA replication on mRNA noise
Open accessAbstract
There are several sources of fluctuations in gene expression. Here we study the effects of time-dependent DNA replication, itself a tightly controlled process, on noise in mRNA levels. Stochastic simulations of constitutive and regulated gene expression are used to analyze the time-averaged mean and variation in each case. The simulations demonstrate that to capture mRNA distributions correctly, chromosome replication must be realistically modeled. Slow relaxation of mRNA from the low copy number steady state before gene replication to the high steady state after replication is set by the transcript's half-life and contributes significantly to the shape of the mRNA distribution. Consequently both the intrinsic kinetics and the gene location play an important role in accounting for the mRNA average and variance. Exact analytic expressions for moments of the mRNA distributions that depend on the DNA copy number, gene location, cell doubling time, and the rates of transcription and degradation are derived for the case of constitutive expression and subsequently extended to provide approximate corrections for regulated expression and RNA polymerase variability. Comparisons of the simulated models and analytical expressions to experimentally measured mRNA distributions show that they better capture the physics of the system than previous theories.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In an earlier work, the authors showed experimentally, theoretically, and computationally the effects of DNA replication or gene copy number on the variance in mRNA distributions and ultimately the protein distributions, and this prior study guided the development of the kinetic model.
“In an earlier work (Peterson et al., 2015), we showed experimentally, theoretically, and computationally the effects of DNA replication or gene copy number on the variance in mRNA distributions and ultimately the protein distributions, and this prior study guided the development of the kinetic model.”
From Fundamental behaviors emerge from simulations of a living minimal cell (2022) · cites this paper as Peterson et al., 2015
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 39 · Cited by 46
Research works printed but not linked: 1
- [39]Peterson JR, Hallock MJ, Cole JA, Luthey-Schulten Z. 2013. A problem solving environment for stochastic biological simulations. PyHPC '13: Proceedings of the 3rd Workshop on Python for High-Performance and Scientific Computing (Association for Computing Machinery, New York)
- Authors
- Peterson, J. R., Cole, J. A., Fei, J., Ha, T., & Luthey-Schulten, Z. A.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-12-15
- Volume
- 112
- Issue
- 52
- Pages
- 15886-15891
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4702981
- OpenAlex
- W2215246329
- Cited by
- 46
- References
- 39
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 3
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (DGE-1144245, PHY-1430124)
- HHS | National Institutes of Health (GM112659, 9 P41 GM104601-23)
- Topics
- 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
- Physical Sciences › Mathematics › Mathematical Physics › Stochastic processes and statistical mechanics
- Keywords
- DNA replication, gene expression fluctuations, stochastic gene expression, mRNA half-life, DNA copy number, gene localization, cell cycle, constitutive expression, regulated gene expression, cell doubling time
- MeSH terms
- Algorithms, DNA, DNA Replication, Gene Expression Regulation, Kinetics, Models, Genetic, DNA-Directed RNA Polymerases, RNA, Messenger, Stochastic Processes, Time Factors, Gene Dosage
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
