Cargando…

Noise in gene expression is coupled to growth rate

Genetically identical cells exposed to the same environment display variability in gene expression (noise), with important consequences for the fidelity of cellular regulation and biological function. Although population average gene expression is tightly coupled to growth rate, the effects of chang...

Descripción completa

Detalles Bibliográficos
Autores principales: Keren, Leeat, van Dijk, David, Weingarten-Gabbay, Shira, Davidi, Dan, Jona, Ghil, Weinberger, Adina, Milo, Ron, Segal, Eran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665010/
https://www.ncbi.nlm.nih.gov/pubmed/26355006
http://dx.doi.org/10.1101/gr.191635.115
_version_ 1782403533015875584
author Keren, Leeat
van Dijk, David
Weingarten-Gabbay, Shira
Davidi, Dan
Jona, Ghil
Weinberger, Adina
Milo, Ron
Segal, Eran
author_facet Keren, Leeat
van Dijk, David
Weingarten-Gabbay, Shira
Davidi, Dan
Jona, Ghil
Weinberger, Adina
Milo, Ron
Segal, Eran
author_sort Keren, Leeat
collection PubMed
description Genetically identical cells exposed to the same environment display variability in gene expression (noise), with important consequences for the fidelity of cellular regulation and biological function. Although population average gene expression is tightly coupled to growth rate, the effects of changes in environmental conditions on expression variability are not known. Here, we measure the single-cell expression distributions of approximately 900 Saccharomyces cerevisiae promoters across four environmental conditions using flow cytometry, and find that gene expression noise is tightly coupled to the environment and is generally higher at lower growth rates. Nutrient-poor conditions, which support lower growth rates, display elevated levels of noise for most promoters, regardless of their specific expression values. We present a simple model of noise in expression that results from having an asynchronous population, with cells at different cell-cycle stages, and with different partitioning of the cells between the stages at different growth rates. This model predicts non-monotonic global changes in noise at different growth rates as well as overall higher variability in expression for cell-cycle–regulated genes in all conditions. The consistency between this model and our data, as well as with noise measurements of cells growing in a chemostat at well-defined growth rates, suggests that cell-cycle heterogeneity is a major contributor to gene expression noise. Finally, we identify gene and promoter features that play a role in gene expression noise across conditions. Our results show the existence of growth-related global changes in gene expression noise and suggest their potential phenotypic implications.
format Online
Article
Text
id pubmed-4665010
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-46650102016-06-01 Noise in gene expression is coupled to growth rate Keren, Leeat van Dijk, David Weingarten-Gabbay, Shira Davidi, Dan Jona, Ghil Weinberger, Adina Milo, Ron Segal, Eran Genome Res Research Genetically identical cells exposed to the same environment display variability in gene expression (noise), with important consequences for the fidelity of cellular regulation and biological function. Although population average gene expression is tightly coupled to growth rate, the effects of changes in environmental conditions on expression variability are not known. Here, we measure the single-cell expression distributions of approximately 900 Saccharomyces cerevisiae promoters across four environmental conditions using flow cytometry, and find that gene expression noise is tightly coupled to the environment and is generally higher at lower growth rates. Nutrient-poor conditions, which support lower growth rates, display elevated levels of noise for most promoters, regardless of their specific expression values. We present a simple model of noise in expression that results from having an asynchronous population, with cells at different cell-cycle stages, and with different partitioning of the cells between the stages at different growth rates. This model predicts non-monotonic global changes in noise at different growth rates as well as overall higher variability in expression for cell-cycle–regulated genes in all conditions. The consistency between this model and our data, as well as with noise measurements of cells growing in a chemostat at well-defined growth rates, suggests that cell-cycle heterogeneity is a major contributor to gene expression noise. Finally, we identify gene and promoter features that play a role in gene expression noise across conditions. Our results show the existence of growth-related global changes in gene expression noise and suggest their potential phenotypic implications. Cold Spring Harbor Laboratory Press 2015-12 /pmc/articles/PMC4665010/ /pubmed/26355006 http://dx.doi.org/10.1101/gr.191635.115 Text en © 2015 Keren et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Keren, Leeat
van Dijk, David
Weingarten-Gabbay, Shira
Davidi, Dan
Jona, Ghil
Weinberger, Adina
Milo, Ron
Segal, Eran
Noise in gene expression is coupled to growth rate
title Noise in gene expression is coupled to growth rate
title_full Noise in gene expression is coupled to growth rate
title_fullStr Noise in gene expression is coupled to growth rate
title_full_unstemmed Noise in gene expression is coupled to growth rate
title_short Noise in gene expression is coupled to growth rate
title_sort noise in gene expression is coupled to growth rate
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665010/
https://www.ncbi.nlm.nih.gov/pubmed/26355006
http://dx.doi.org/10.1101/gr.191635.115
work_keys_str_mv AT kerenleeat noiseingeneexpressioniscoupledtogrowthrate
AT vandijkdavid noiseingeneexpressioniscoupledtogrowthrate
AT weingartengabbayshira noiseingeneexpressioniscoupledtogrowthrate
AT davididan noiseingeneexpressioniscoupledtogrowthrate
AT jonaghil noiseingeneexpressioniscoupledtogrowthrate
AT weinbergeradina noiseingeneexpressioniscoupledtogrowthrate
AT miloron noiseingeneexpressioniscoupledtogrowthrate
AT segaleran noiseingeneexpressioniscoupledtogrowthrate