skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Mutations in global regulators lead to metabolic selection during adaptation to complex environments

Abstract

Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Unlike adaptation to a single limiting resource, adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes since many mutations are required to achieve even modest gains in fitness. Since changing complex environments are quite common in nature, we investigated how such an epistatic bottleneck can be avoided to allow rapid adaptation. We show that adaptive mutations arise repeatedly in independently evolved populations in the context of greatly increased genetic and phenotypic diversity. We go on to show that weak selection requiring substantial metabolic reprogramming can be readily achieved by mutations in the global response regulator arcA and the stress response regulator rpoS. We identified 46 unique single-nucleotide variants of arcA and 18 mutations in rpoS, nine of which resulted in stop codons or large deletions, suggesting that a subtle modulation of ArcA function and knockouts of rpoS are largely responsible for the metabolic shifts leading to adaptation. These mutations allow a higher order “metabolic selection” that eliminates epistatic bottlenecks, which could occur when many changes would be required. Proteomicmore » and carbohydrate analysis of adapting E. coli populations revealed an up-regulation of enzymes associated with the TCA cycle and amino acid metabolism and an increase in the secretion of putrescine. The overall effect of adaptation across populations is to redirect and efficiently utilize uptake and catabolism of abundant amino acids. Concomitantly, there is a pronounced spread of more ecologically limited strains that results from specialization through metabolic erosion. Remarkably, the global regulators arcA and rpoS can provide a “one-step” mechanism of adaptation to a novel environment, which highlights the importance of global resource management as a powerful strategy to adaptation.« less

Authors:
 [1];  [2];  [3];  [3];  [3];  [1];  [1];  [1];  [1];  [4];  [1];  [5];  [3];  [1];  [6]
  1. Rice Univ., Houston, TX (United States)
  2. United States Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, MD (United States); EXCET, Inc., Springfield, VA (United Kingdom)
  3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  4. Northern Arizona Univ., Flagstaff, AZ (United States)
  5. United States Army Edgewood Chemical Biological Center, Aberdeen Proving Ground, MD (United States)
  6. Univ. Paris Descartes (France)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1166862
Report Number(s):
PNNL-SA-106551
Journal ID: ISSN 1553-7404; 400403909
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
PLoS Genetics
Additional Journal Information:
Journal Volume: 10; Journal Issue: 12; Journal ID: ISSN 1553-7404
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; proteomics; genome analysis; serial passage; laboratory evolution; Escherichia coli; adaptation

Citation Formats

Saxer, Gerda, Krepps, Michael D., Merkley, Eric D., Ansong, Charles, Deatherage Kaiser, Brooke L., Valovska, Marie -Thérèse, Ristic, Nikola, Yeh, Ping T., Prakash, Vittal P., Leiser, Owen P., Nakhleh, Luay, Gibbons, Henry S., Kreuzer, Helen W., Shamoo, Yousif, and Matic, Ivan. Mutations in global regulators lead to metabolic selection during adaptation to complex environments. United States: N. p., 2014. Web. doi:10.1371/journal.pgen.1004872.
Saxer, Gerda, Krepps, Michael D., Merkley, Eric D., Ansong, Charles, Deatherage Kaiser, Brooke L., Valovska, Marie -Thérèse, Ristic, Nikola, Yeh, Ping T., Prakash, Vittal P., Leiser, Owen P., Nakhleh, Luay, Gibbons, Henry S., Kreuzer, Helen W., Shamoo, Yousif, & Matic, Ivan. Mutations in global regulators lead to metabolic selection during adaptation to complex environments. United States. doi:10.1371/journal.pgen.1004872.
Saxer, Gerda, Krepps, Michael D., Merkley, Eric D., Ansong, Charles, Deatherage Kaiser, Brooke L., Valovska, Marie -Thérèse, Ristic, Nikola, Yeh, Ping T., Prakash, Vittal P., Leiser, Owen P., Nakhleh, Luay, Gibbons, Henry S., Kreuzer, Helen W., Shamoo, Yousif, and Matic, Ivan. Thu . "Mutations in global regulators lead to metabolic selection during adaptation to complex environments". United States. doi:10.1371/journal.pgen.1004872. https://www.osti.gov/servlets/purl/1166862.
@article{osti_1166862,
title = {Mutations in global regulators lead to metabolic selection during adaptation to complex environments},
author = {Saxer, Gerda and Krepps, Michael D. and Merkley, Eric D. and Ansong, Charles and Deatherage Kaiser, Brooke L. and Valovska, Marie -Thérèse and Ristic, Nikola and Yeh, Ping T. and Prakash, Vittal P. and Leiser, Owen P. and Nakhleh, Luay and Gibbons, Henry S. and Kreuzer, Helen W. and Shamoo, Yousif and Matic, Ivan},
abstractNote = {Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Unlike adaptation to a single limiting resource, adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes since many mutations are required to achieve even modest gains in fitness. Since changing complex environments are quite common in nature, we investigated how such an epistatic bottleneck can be avoided to allow rapid adaptation. We show that adaptive mutations arise repeatedly in independently evolved populations in the context of greatly increased genetic and phenotypic diversity. We go on to show that weak selection requiring substantial metabolic reprogramming can be readily achieved by mutations in the global response regulator arcA and the stress response regulator rpoS. We identified 46 unique single-nucleotide variants of arcA and 18 mutations in rpoS, nine of which resulted in stop codons or large deletions, suggesting that a subtle modulation of ArcA function and knockouts of rpoS are largely responsible for the metabolic shifts leading to adaptation. These mutations allow a higher order “metabolic selection” that eliminates epistatic bottlenecks, which could occur when many changes would be required. Proteomic and carbohydrate analysis of adapting E. coli populations revealed an up-regulation of enzymes associated with the TCA cycle and amino acid metabolism and an increase in the secretion of putrescine. The overall effect of adaptation across populations is to redirect and efficiently utilize uptake and catabolism of abundant amino acids. Concomitantly, there is a pronounced spread of more ecologically limited strains that results from specialization through metabolic erosion. Remarkably, the global regulators arcA and rpoS can provide a “one-step” mechanism of adaptation to a novel environment, which highlights the importance of global resource management as a powerful strategy to adaptation.},
doi = {10.1371/journal.pgen.1004872},
journal = {PLoS Genetics},
issn = {1553-7404},
number = 12,
volume = 10,
place = {United States},
year = {2014},
month = {12}
}

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

Citation Metrics:
Cited by: 12 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

The RAST Server: Rapid Annotations using Subsystems Technology
journal, January 2008

  • Aziz, Ramy K.; Bartels, Daniela; Best, Aaron A.
  • BMC Genomics, Vol. 9, Issue 1, Article No. 75
  • DOI: 10.1186/1471-2164-9-75

The Molecular Diversity of Adaptive Convergence
journal, January 2012

  • Tenaillon, O.; Rodriguez-Verdugo, A.; Gaut, R. L.
  • Science, Vol. 335, Issue 6067, p. 457-461
  • DOI: 10.1126/science.1212986

Global metabolic regulation analysis for Escherichia coli K12 based on protein expression by 2-dimensional electrophoresis and enzyme activity measurement
journal, January 2003


Evolutionary paths to antibiotic resistance under dynamically sustained drug selection
journal, December 2011

  • Toprak, Erdal; Veres, Adrian; Michel, Jean-Baptiste
  • Nature Genetics, Vol. 44, Issue 1, p. 101-105
  • DOI: 10.1038/ng.1034