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

PLoS Genet. 2014 Dec 11;10(12):e1004872. doi: 10.1371/journal.pgen.1004872. eCollection 2014 Dec.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Biological / genetics
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Proteins / genetics
  • Citric Acid Cycle / genetics
  • Citrobacter freundii / genetics*
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / genetics
  • Evolution, Molecular*
  • Gastrointestinal Tract / microbiology
  • Gene Expression Regulation, Bacterial
  • Gene-Environment Interaction
  • Genetic Variation
  • Humans
  • Mutation
  • Phenotype
  • Proteome / genetics
  • Proteome / metabolism
  • Repressor Proteins / genetics
  • Sigma Factor / genetics
  • Up-Regulation

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Escherichia coli Proteins
  • Proteome
  • Repressor Proteins
  • Sigma Factor
  • arcA protein, E coli
  • sigma factor KatF protein, Bacteria

Grant support

This work was supported by funding from the Defense Threat Reduction Agency (HDTRA-1-10-1-0069) to YS and (DTRA10027IA-2129) to HWK. Pacific Northwest National Laboratory is operated by Battelle Memorial Institute for the U.S. Department of Energy under contract DE-AC06-76RLO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.