DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Distribution and regulation of stochasticity and plasticity in Saccharomyces cerevisiae

Abstract

Stochasticity is an inherent feature of complex systems with nanoscale structure. In such systems information is represented by small collections of elements (e.g. a few electrons on a quantum dot), and small variations in the populations of these elements may lead to big uncertainties in the information. Unfortunately, little is known about how to work within this inherently noisy environment to design robust functionality into complex nanoscale systems. Here, we look to the biological cell as an intriguing model system where evolution has mediated the trade-offs between fluctuations and function, and in particular we look at the relationships and trade-offs between stochastic and deterministic responses in the gene expression of budding yeast (Saccharomyces cerevisiae). We find gene regulatory arrangements that control the stochastic and deterministic components of expression, and show that genes that have evolved to respond to stimuli (stress) in the most strongly deterministic way exhibit the most noise in the absence of the stimuli. We show that this relationship is consistent with a bursty 2-state model of gene expression, and demonstrate that this regulatory motif generates the most uncertainty in gene expression when there is the greatest uncertainty in the optimal level of gene expression.

Authors:
 [1];  [1];  [2];  [1];  [1]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
  2. Univ. of Tennessee, Knoxville, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1076448
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Chaos: An Interdisciplinary Journal of Nonlinear Science
Additional Journal Information:
Journal Volume: 20; Journal Issue: 3; Journal ID: ISSN 1054-1500
Publisher:
American Institute of Physics (AIP)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; SACCHAROMYCES CEREVISIAE; TRANSCRIPTIONAL PLASTICITY; GENE EXPRESSION NOISE; GENE CIRCUIT FLUCTUATION ANALYSIS; REGULATORY ARCHITECTURE; STRESS RESPONSE

Citation Formats

Dar, R. D., Karig, D. K., Cooke, J. F., Cox, C. D., and Simpson, M. L. Distribution and regulation of stochasticity and plasticity in Saccharomyces cerevisiae. United States: N. p., 2010. Web. doi:10.1063/1.3486800.
Dar, R. D., Karig, D. K., Cooke, J. F., Cox, C. D., & Simpson, M. L. Distribution and regulation of stochasticity and plasticity in Saccharomyces cerevisiae. United States. https://doi.org/10.1063/1.3486800
Dar, R. D., Karig, D. K., Cooke, J. F., Cox, C. D., and Simpson, M. L. Wed . "Distribution and regulation of stochasticity and plasticity in Saccharomyces cerevisiae". United States. https://doi.org/10.1063/1.3486800. https://www.osti.gov/servlets/purl/1076448.
@article{osti_1076448,
title = {Distribution and regulation of stochasticity and plasticity in Saccharomyces cerevisiae},
author = {Dar, R. D. and Karig, D. K. and Cooke, J. F. and Cox, C. D. and Simpson, M. L.},
abstractNote = {Stochasticity is an inherent feature of complex systems with nanoscale structure. In such systems information is represented by small collections of elements (e.g. a few electrons on a quantum dot), and small variations in the populations of these elements may lead to big uncertainties in the information. Unfortunately, little is known about how to work within this inherently noisy environment to design robust functionality into complex nanoscale systems. Here, we look to the biological cell as an intriguing model system where evolution has mediated the trade-offs between fluctuations and function, and in particular we look at the relationships and trade-offs between stochastic and deterministic responses in the gene expression of budding yeast (Saccharomyces cerevisiae). We find gene regulatory arrangements that control the stochastic and deterministic components of expression, and show that genes that have evolved to respond to stimuli (stress) in the most strongly deterministic way exhibit the most noise in the absence of the stimuli. We show that this relationship is consistent with a bursty 2-state model of gene expression, and demonstrate that this regulatory motif generates the most uncertainty in gene expression when there is the greatest uncertainty in the optimal level of gene expression.},
doi = {10.1063/1.3486800},
journal = {Chaos: An Interdisciplinary Journal of Nonlinear Science},
number = 3,
volume = 20,
place = {United States},
year = {2010},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 5 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Using noise to probe and characterize gene circuits
journal, July 2008

  • Cox, C. D.; McCollum, J. M.; Allen, M. S.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 31
  • DOI: 10.1073/pnas.0804829105

Microbial cell individuality and the underlying sources of heterogeneity
journal, August 2006


Stochastic Gene Expression in a Single Cell
journal, August 2002


Non-genetic individuality: chance in the single cell
journal, August 1976

  • Spudich, John L.; Koshland, D. E.
  • Nature, Vol. 262, Issue 5568
  • DOI: 10.1038/262467a0

A Genome-Wide Housekeeping Role for TFIID and a Highly Regulated Stress-Related Role for SAGA in Saccharomyces cerevisiae
journal, February 2004


Genomic Expression Programs in the Response of Yeast Cells to Environmental Changes
journal, December 2000

  • Gasch, Audrey P.; Spellman, Paul T.; Kao, Camilla M.
  • Molecular Biology of the Cell, Vol. 11, Issue 12
  • DOI: 10.1091/mbc.11.12.4241

Stochasticity in Transcriptional Regulation: Origins, Consequences, and Mathematical Representations
journal, December 2001


Network Inference, Analysis, and Modeling in Systems Biology
journal, November 2007


Stochastic Gene Expression in Fluctuating Environments
journal, May 2004


Origins of extrinsic variability in eukaryotic gene expression
journal, December 2005

  • Volfson, Dmitri; Marciniak, Jennifer; Blake, William J.
  • Nature, Vol. 439, Issue 7078
  • DOI: 10.1038/nature04281

Dynamic proteomics in individual human cells uncovers widespread cell-cycle dependence of nuclear proteins
journal, June 2006

  • Sigal, Alex; Milo, Ron; Cohen, Ariel
  • Nature Methods, Vol. 3, Issue 7
  • DOI: 10.1038/nmeth892

Gene Regulation at the Single-Cell Level
journal, March 2005


Noise Minimization in Eukaryotic Gene Expression
journal, April 2004


Control of Stochasticity in Eukaryotic Gene Expression
journal, June 2004


Noise Propagation in Gene Networks
journal, March 2005


Statistical indicators of collective behavior and functional clusters in gene networks of yeast
journal, March 2006


Noise in biological circuits
journal, February 2009

  • Simpson, Michael L.; Cox, Chris D.; Allen, Michael S.
  • Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, Vol. 1, Issue 2
  • DOI: 10.1002/wnan.22

Exact stochastic simulation of coupled chemical reactions
journal, December 1977

  • Gillespie, Daniel T.
  • The Journal of Physical Chemistry, Vol. 81, Issue 25
  • DOI: 10.1021/j100540a008

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

  • Newman, John R. S.; Ghaemmaghami, Sina; Ihmels, Jan
  • Nature, Vol. 441, Issue 7095
  • DOI: 10.1038/nature04785

Phenotypic Consequences of Promoter-Mediated Transcriptional Noise
journal, December 2006


Variability and memory of protein levels in human cells
journal, November 2006


Tunability and Noise Dependence in Differentiation Dynamics
journal, March 2007


Regulated cell-to-cell variation in a cell-fate decision system
journal, September 2005

  • Colman-Lerner, Alejandro; Gordon, Andrew; Serra, Eduard
  • Nature, Vol. 437, Issue 7059
  • DOI: 10.1038/nature03998

Engineering stability in gene networks by autoregulation
journal, June 2000

  • Becskei, Attila; Serrano, Luis
  • Nature, Vol. 405, Issue 6786
  • DOI: 10.1038/35014651

Transient-mediated fate determination in a transcriptional circuit of HIV
journal, March 2008

  • Weinberger, Leor S.; Dar, Roy D.; Simpson, Michael L.
  • Nature Genetics, Vol. 40, Issue 4
  • DOI: 10.1038/ng.116

A Regulatory Network Analysis of Phenotypic Plasticity in Yeast
journal, May 2005

  • Promislow, Daniel
  • The American Naturalist, Vol. 165, Issue 5
  • DOI: 10.1086/429161

Noise in protein expression scales with natural protein abundance
journal, May 2006

  • Bar-Even, Arren; Paulsson, Johan; Maheshri, Narendra
  • Nature Genetics, Vol. 38, Issue 6
  • DOI: 10.1038/ng1807

Identification and Distinct Regulation of Yeast TATA Box-Containing Genes
journal, March 2004


Genetic Properties Influencing the Evolvability of Gene Expression
journal, July 2007


Transcriptional Bursting from the HIV-1 Promoter Is a Significant Source of Stochastic Noise in HIV-1 Gene Expression
journal, April 2010


Nano‐enabled synthetic biology
journal, January 2007

  • Doktycz, Mitchel J.; Simpson, Michael L.
  • Molecular Systems Biology, Vol. 3, Issue 1
  • DOI: 10.1038/msb4100165

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

  • Acar, Murat; Mettetal, Jerome T.; van Oudenaarden, Alexander
  • Nature Genetics, Vol. 40, Issue 4
  • DOI: 10.1038/ng.110

Frequency domain chemical Langevin analysis of stochasticity in gene transcriptional regulation
journal, August 2004

  • Simpson, Michael L.; Cox, Chris D.; Sayler, Gary S.
  • Journal of Theoretical Biology, Vol. 229, Issue 3
  • DOI: 10.1016/j.jtbi.2004.04.017

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


A high-resolution atlas of nucleosome occupancy in yeast
journal, September 2007

  • Lee, William; Tillo, Desiree; Bray, Nicolas
  • Nature Genetics, Vol. 39, Issue 10
  • DOI: 10.1038/ng2117

Phenotypic Diversity, Population Growth, and Information in Fluctuating Environments
journal, September 2005


Gene network shaping of inherent noise spectra
journal, February 2006

  • Austin, D. W.; Allen, M. S.; McCollum, J. M.
  • Nature, Vol. 439, Issue 7076
  • DOI: 10.1038/nature04194

Noise in eukaryotic gene expression
journal, April 2003

  • Blake, William J.; KÆrn, Mads; Cantor, Charles R.
  • Nature, Vol. 422, Issue 6932
  • DOI: 10.1038/nature01546

Genome‐wide transcriptional plasticity underlies cellular adaptation to novel challenge
journal, January 2007

  • Stern, Shay; Dror, Tali; Stolovicki, Elad
  • Molecular Systems Biology, Vol. 3, Issue 1
  • DOI: 10.1038/msb4100147

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

  • Ozbudak, Ertugrul M.; Thattai, Mukund; Kurtser, Iren
  • Nature Genetics, Vol. 31, Issue 1
  • DOI: 10.1038/ng869

Works referencing / citing this record:

High-Throughput Yeast Aging Analysis for Cryptococcus (HYAAC) microfluidic device streamlines aging studies in Cryptococcus neoformans
journal, July 2019


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

  • Megaridis, Melina R.; Lu, Yiyang; Tevonian, Erin N.
  • APL Bioengineering, Vol. 2, Issue 2
  • DOI: 10.1063/1.5021183

Perspective: Engineering noise in biological systems towards predictive stochastic design
journal, June 2018


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