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Title: Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution

Abstract

Pleiotropic regulatory mutations affect diverse cellular processes, posing a challenge to our understanding of genotype-phenotype relationships across multiple biological scales. Adaptive laboratory evolution (ALE) allows for such mutations to be found and characterized in the context of clear selection pressures. Here, several ALE-selected single-mutation variants in RNA polymerase (RNAP) of Escherichia coli are detailed using an integrated multi-scale experimental and computational approach. While these mutations increase cellular growth rates in steady environments, they reduce tolerance to stress and environmental fluctuations. We detail structural changes in the RNAP that rewire the transcriptional machinery to rebalance proteome and energy allocation toward growth and away from several hedging and stress functions. We find that while these mutations occur in diverse locations in the RNAP, they share a common adaptive mechanism. In turn, these findings highlight the resource allocation trade-offs organisms face and suggest how the structure of the regulatory network enhances evolvability.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1353268
Alternate Identifier(s):
OSTI ID: 1543519
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Published Article
Journal Name:
Cell Systems
Additional Journal Information:
Journal Name: Cell Systems Journal Volume: 2 Journal Issue: 4; Journal ID: ISSN 2405-4712
Publisher:
Elsevier
Country of Publication:
Niger
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biochemistry & Molecular Biology; Cell Biology

Citation Formats

Utrilla, Jose, O’Brien, Edward J., Chen, Ke, McCloskey, Douglas, Cheung, Jacky, Wang, Harris, Armenta-Medina, Dagoberto, Feist, Adam M., and Palsson, Bernhard O. Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution. Niger: N. p., 2016. Web. doi:10.1016/j.cels.2016.04.003.
Utrilla, Jose, O’Brien, Edward J., Chen, Ke, McCloskey, Douglas, Cheung, Jacky, Wang, Harris, Armenta-Medina, Dagoberto, Feist, Adam M., & Palsson, Bernhard O. Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution. Niger. doi:10.1016/j.cels.2016.04.003.
Utrilla, Jose, O’Brien, Edward J., Chen, Ke, McCloskey, Douglas, Cheung, Jacky, Wang, Harris, Armenta-Medina, Dagoberto, Feist, Adam M., and Palsson, Bernhard O. Fri . "Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution". Niger. doi:10.1016/j.cels.2016.04.003.
@article{osti_1353268,
title = {Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution},
author = {Utrilla, Jose and O’Brien, Edward J. and Chen, Ke and McCloskey, Douglas and Cheung, Jacky and Wang, Harris and Armenta-Medina, Dagoberto and Feist, Adam M. and Palsson, Bernhard O.},
abstractNote = {Pleiotropic regulatory mutations affect diverse cellular processes, posing a challenge to our understanding of genotype-phenotype relationships across multiple biological scales. Adaptive laboratory evolution (ALE) allows for such mutations to be found and characterized in the context of clear selection pressures. Here, several ALE-selected single-mutation variants in RNA polymerase (RNAP) of Escherichia coli are detailed using an integrated multi-scale experimental and computational approach. While these mutations increase cellular growth rates in steady environments, they reduce tolerance to stress and environmental fluctuations. We detail structural changes in the RNAP that rewire the transcriptional machinery to rebalance proteome and energy allocation toward growth and away from several hedging and stress functions. We find that while these mutations occur in diverse locations in the RNAP, they share a common adaptive mechanism. In turn, these findings highlight the resource allocation trade-offs organisms face and suggest how the structure of the regulatory network enhances evolvability.},
doi = {10.1016/j.cels.2016.04.003},
journal = {Cell Systems},
number = 4,
volume = 2,
place = {Niger},
year = {2016},
month = {4}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.cels.2016.04.003

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Cited by: 15 works
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Works referencing / citing this record:

How does mutation affect the distribution of phenotypes?: TESTING FOR MUTATIONAL BIAS
journal, September 2017


Generation of an E. coli platform strain for improved sucrose utilization using adaptive laboratory evolution
journal, June 2019

  • Mohamed, Elsayed T.; Mundhada, Hemanshu; Landberg, Jenny
  • Microbial Cell Factories, Vol. 18, Issue 1
  • DOI: 10.1186/s12934-019-1165-2

How does mutation affect the distribution of phenotypes?: TESTING FOR MUTATIONAL BIAS
journal, September 2017


Generation of an E. coli platform strain for improved sucrose utilization using adaptive laboratory evolution
journal, June 2019

  • Mohamed, Elsayed T.; Mundhada, Hemanshu; Landberg, Jenny
  • Microbial Cell Factories, Vol. 18, Issue 1
  • DOI: 10.1186/s12934-019-1165-2