Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments

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dc.citation.firstpagee1004872en_US
dc.citation.issueNumber12en_US
dc.citation.journalTitlePLoS Geneticsen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorSaxer, Gerdaen_US
dc.contributor.authorKrepps, Michael D.en_US
dc.contributor.authorMerkley, Eric D.en_US
dc.contributor.authorAnsong, Charlesen_US
dc.contributor.authorDeatherage Kaiser, Brooke L.en_US
dc.contributor.authorValovska, Marie-Thérèseen_US
dc.contributor.authorRistic, Nikolaen_US
dc.contributor.authorYeh, Ping T.en_US
dc.contributor.authorPrakash, Vittal P.en_US
dc.contributor.authorLeiser, Owen P.en_US
dc.contributor.authorNakhleh, Luay K.en_US
dc.contributor.authorGibbons, Henry S.en_US
dc.contributor.authorKreuzer, Helen W.en_US
dc.contributor.authorShamoo, Yousifen_US
dc.date.accessioned2015-02-02T18:00:46Zen_US
dc.date.available2015-02-02T18:00:46Zen_US
dc.date.issued2014en_US
dc.description.abstractAdaptation 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.en_US
dc.identifier.citationSaxer, Gerda, Krepps, Michael D., Merkley, Eric D., et al.. "Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments." <i>PLoS Genetics,</i> 10, no. 12 (2014) Public Library of Science: e1004872. http://dx.doi.org/10.1371/journal.pgen.1004872.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pgen.1004872en_US
dc.identifier.urihttps://hdl.handle.net/1911/79021en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis 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.en_US
dc.rights.urihttps://creativecommons.org/publicdomain/zero/1.0/en_US
dc.titleMutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environmentsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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