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dc.contributor.authorSaxer, 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, You
dc.date.accessioned 2015-02-02T18:00:46Z
dc.date.available 2015-02-02T18:00:46Z
dc.date.issued 2014
dc.identifier.citation Saxer, Gerda, Krepps, Michael D., Merkley, Eric D., et al.. "Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments." PLoS Genetics, 10, no. 12 (2014) Public Library of Science: e1004872. http://dx.doi.org/10.1371/journal.pgen.1004872.
dc.identifier.urihttps://hdl.handle.net/1911/79021
dc.description.abstract Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes if 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 subtle modulations 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.
dc.language.iso eng
dc.publisher Public Library of Science
dc.rights This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
dc.rights.urihttps://creativecommons.org/publicdomain/zero/1.0/
dc.title Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments
dc.type Journal article
dc.contributor.funder Defense Threat Reduction Agency
dc.contributor.funder U.S. Department of Energy
dc.citation.journalTitle PLoS Genetics
dc.citation.volumeNumber 10
dc.citation.issueNumber 12
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pgen.1004872
dc.identifier.pmcid PMC4263409
dc.identifier.pmid 25501822
dc.identifier.grantID HDTRA-1-10-1-0069 (Defense Threat Reduction Agency)
dc.identifier.grantID DTRA10027IA-2129 (Defense Threat Reduction Agency)
dc.identifier.grantID DE-AC06-76RLO (U.S. Department of Energy)
dc.type.publication publisher version
dc.citation.firstpage e1004872


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This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Except where otherwise noted, this item's license is described as This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.