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

Journal Article · Thu Dec 11 00:00:00 EST 2014 · PLoS Genetics

DOI:https://doi.org/10.1371/journal.pgen.1004872· OSTI ID:1166862

Saxer, Gerda ^[1]; Krepps, Michael D. ^[2]; Merkley, Eric D. ^[3]; Ansong, Charles ^[3]; Deatherage Kaiser, Brooke L. ^[3]; Valovska, Marie -Thérèse ^[1]; Ristic, Nikola ^[1]; Yeh, Ping T. ^[1]; Prakash, Vittal P. ^[1]; Leiser, Owen P. ^[4]; Nakhleh, Luay ^[1]; Gibbons, Henry S. ^[5]; Kreuzer, Helen W. ^[3]; Shamoo, Yousif ^[1]; Matic, Ivan ^[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)

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.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• Grant/Contract Number: AC05-76RL01830
• OSTI ID: 1166862
• Report Number(s): PNNL-SA-106551; 400403909
• Journal Information: PLoS Genetics, Vol. 10, Issue 12; ISSN 1553-7404
• Publisher: Public Library of Science
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
proteomics
genome analysis
serial passage
laboratory evolution
Escherichia coli
adaptation