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Title: The low noise limit in gene expression

Abstract

Protein noise measurements are increasingly used to elucidate biophysical parameters. Unfortunately noise analyses are often at odds with directly measured parameters. Here we show that these inconsistencies arise from two problematic analytical choices: (i) the assumption that protein translation rate is invariant for different proteins of different abundances, which has inadvertently led to (ii) the assumption that a large constitutive extrinsic noise sets the low noise limit in gene expression. While growing evidence suggests that transcriptional bursting may set the low noise limit, variability in translational bursting has been largely ignored. We show that genome-wide systematic variation in translational efficiency can-and in the case of E. coli does-control the low noise limit in gene expression. Therefore constitutive extrinsic noise is small and only plays a role in the absence of a systematic variation in translational efficiency. Lastly, these results show the existence of two distinct expression noise patterns: (1) a global noise floor uniformly imposed on all genes by expression bursting; and (2) high noise distributed to only a select group of genes.

Authors:
 [1];  [2];  [3];  [4];  [5]
  1. Gladstone Institute of Virology and Immunology, San Francisco, CA (United States); Univ. of Illinois at Urbana-Champaign, Urbana, IL (United States)
  2. Gladstone Institute of Virology and Immunology, San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States)
  3. Univ. of Tennessee, Knoxville, TN (United States)
  4. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
  5. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States); The Rockefeller Univ., New York, NY (United States)
Publication Date:
Research Org.:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1255649
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 10; Journal Issue: 10; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; gene expression; E. coli; transcriptional bursting; translational bursting; extrinsic noise; messenger RNA; saccharomyces cerevisiae; protein translation; protein abundance; DNA transcription; bacterial genomics; T cells

Citation Formats

Dar, Roy D., Weinberger, Leor S., Cox, Chris D., Simpson, Michael L., and Razooky, Brandon S. The low noise limit in gene expression. United States: N. p., 2015. Web. doi:10.1371/journal.pone.0140969.
Dar, Roy D., Weinberger, Leor S., Cox, Chris D., Simpson, Michael L., & Razooky, Brandon S. The low noise limit in gene expression. United States. https://doi.org/10.1371/journal.pone.0140969
Dar, Roy D., Weinberger, Leor S., Cox, Chris D., Simpson, Michael L., and Razooky, Brandon S. 2015. "The low noise limit in gene expression". United States. https://doi.org/10.1371/journal.pone.0140969. https://www.osti.gov/servlets/purl/1255649.
@article{osti_1255649,
title = {The low noise limit in gene expression},
author = {Dar, Roy D. and Weinberger, Leor S. and Cox, Chris D. and Simpson, Michael L. and Razooky, Brandon S.},
abstractNote = {Protein noise measurements are increasingly used to elucidate biophysical parameters. Unfortunately noise analyses are often at odds with directly measured parameters. Here we show that these inconsistencies arise from two problematic analytical choices: (i) the assumption that protein translation rate is invariant for different proteins of different abundances, which has inadvertently led to (ii) the assumption that a large constitutive extrinsic noise sets the low noise limit in gene expression. While growing evidence suggests that transcriptional bursting may set the low noise limit, variability in translational bursting has been largely ignored. We show that genome-wide systematic variation in translational efficiency can-and in the case of E. coli does-control the low noise limit in gene expression. Therefore constitutive extrinsic noise is small and only plays a role in the absence of a systematic variation in translational efficiency. Lastly, these results show the existence of two distinct expression noise patterns: (1) a global noise floor uniformly imposed on all genes by expression bursting; and (2) high noise distributed to only a select group of genes.},
doi = {10.1371/journal.pone.0140969},
url = {https://www.osti.gov/biblio/1255649}, journal = {PLoS ONE},
issn = {1932-6203},
number = 10,
volume = 10,
place = {United States},
year = {Wed Oct 21 00:00:00 EDT 2015},
month = {Wed Oct 21 00:00:00 EDT 2015}
}

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Free Publicly Available Full Text
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Cited by: 22 works
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Works referenced in this record:

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Gene network shaping of inherent noise spectra
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Influence of mRNA determinants on translation initiation in Escherichia coli
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And the Noise Played on: Stochastic Gene Expression and HIV-1 Infection
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Real-Time Kinetics of Gene Activity in Individual Bacteria
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Microscale and nanoscale compartments for biotechnology
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Budding Yeast Escape Commitment to the Phosphate Starvation Program Using Gene Expression Noise
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Using Dynamic Noise Propagation to Infer Causal Regulatory Relationships in Biochemical Networks
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Stochasticity in Gene Expression in a Cell-Sized Compartment
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Lysogen stability is determined by the frequency of activity bursts from the fate‐determining gene
journal, January 2010


Random timing in signaling cascades
journal, January 2007


Nano‐enabled synthetic biology
journal, January 2007


Summing up the noise in gene networks
journal, January 2004


Gene network shaping of inherent noise spectra
journal, February 2006


Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise
journal, May 2006


A noisy linear map underlies oscillations in cell size and gene expression in bacteria
journal, June 2015


Contribution of RNA polymerase concentration variation to protein expression noise
journal, September 2014


Stochastic switching as a survival strategy in fluctuating environments
journal, March 2008


Non-genetic heterogeneity from stochastic partitioning at cell division
journal, December 2010


General properties of transcriptional time series in Escherichia coli
journal, May 2011


Regulation of noise in the expression of a single gene
journal, April 2002


Single-RNA counting reveals alternative modes of gene expression in yeast
journal, November 2008


Transcription of functionally related constitutive genes is not coordinated
journal, December 2010


Epigenetic Ratchet: Spontaneous Adaptation via Stochastic Gene Expression
journal, January 2020


Distribution and regulation of stochasticity and plasticity in Saccharomyces cerevisiae
journal, September 2010


Precision and functional specificity in mRNA decay
journal, April 2002


Transcriptional burst frequency and burst size are equally modulated across the human genome
journal, October 2012


The 3'-Terminal Sequence of Escherichia coli 16S Ribosomal RNA: Complementarity to Nonsense Triplets and Ribosome Binding Sites
journal, April 1974


Two strategies for gene regulation by promoter nucleosomes
journal, July 2008


Tunability and Noise Dependence in Differentiation Dynamics
journal, March 2007


Effects of Molecular Memory and Bursting on Fluctuations in Gene Expression
journal, January 2008


Mammalian Genes Are Transcribed with Widely Different Bursting Kinetics
journal, March 2011


Real-Time Observation of Transcription Initiation and Elongation on an Endogenous Yeast Gene
journal, April 2011


Genetic Determinants and Cellular Constraints in Noisy Gene Expression
journal, December 2013


Screening for noise in gene expression identifies drug synergies
journal, June 2014


Chance Fluctuations in mRNA Output in Mammalian Cells
journal, September 2006


An HIV Feedback Resistor: Auto-Regulatory Circuit Deactivator and Noise Buffer
journal, December 2006


Dynamic Analysis of Stochastic Transcription Cycles
journal, April 2011


Promoter Sequence Determines the Relationship between Expression Level and Noise
journal, April 2013


The Generation of Promoter-Mediated Transcriptional Noise in Bacteria
journal, July 2008


Mitochondrial Variability as a Source of Extrinsic Cellular Noise
journal, March 2012


Direct observation of frequency modulated transcription in single cells using light activation
journal, September 2013


Works referencing / citing this record:

Fine-tuning of noise in gene expression with nucleosome remodeling
journal, June 2018


3’-5’ crosstalk contributes to transcriptional bursting
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Mammalian gene expression variability is explained by underlying cell state
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3 ′-5 ′ crosstalk contributes to transcriptional bursting
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Fine-tuning of noise in gene expression with nucleosome remodeling
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Translation initiation events on structured eukaryotic mRNAs generate gene expression noise
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