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

Saxer G, Krepps MD, Merkley ED, Ansong C, Deatherage Kaiser BL, Valovska MT, Ristic N, Yeh PT, Prakash VP, Leiser OP, Nakhleh L, Gibbons HS, Kreuzer HW, Shamoo Y - PLoS Genet. (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of BioSciences, Rice University, Houston, Texas, United States of America.

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.

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Frequencies of arcA and rpoS mutants in the evolved populations arcA mutations (black bars) reached high frequencies in all LB-evolved populations (A, B) and reach fixation in LB5, while rpoS mutations (red) were more common in BHI-evolved populations (C, D).The frequencies represent the total frequencies of all arcA or respectively, identified in a particular population.
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pgen-1004872-g006: Frequencies of arcA and rpoS mutants in the evolved populations arcA mutations (black bars) reached high frequencies in all LB-evolved populations (A, B) and reach fixation in LB5, while rpoS mutations (red) were more common in BHI-evolved populations (C, D).The frequencies represent the total frequencies of all arcA or respectively, identified in a particular population.

Mentions: The highly parallel evolution of mutations in arcA and rpoS combined with their global effects suggests that these mutations are driving adaptation in these complex selective environments. Mutations in these genes were very common with multiple different alleles co-occurring within the same population. The cumulative frequencies of arcA mutations in particular reached high frequencies in LB (average 0.75±0.08 (mean and 95%CI) across 24 populations (Fig. 6). In only one population did we observe the fixation of a single arcA mutation (LB5).


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

Saxer G, Krepps MD, Merkley ED, Ansong C, Deatherage Kaiser BL, Valovska MT, Ristic N, Yeh PT, Prakash VP, Leiser OP, Nakhleh L, Gibbons HS, Kreuzer HW, Shamoo Y - PLoS Genet. (2014)

Frequencies of arcA and rpoS mutants in the evolved populations arcA mutations (black bars) reached high frequencies in all LB-evolved populations (A, B) and reach fixation in LB5, while rpoS mutations (red) were more common in BHI-evolved populations (C, D).The frequencies represent the total frequencies of all arcA or respectively, identified in a particular population.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4263409&req=5

pgen-1004872-g006: Frequencies of arcA and rpoS mutants in the evolved populations arcA mutations (black bars) reached high frequencies in all LB-evolved populations (A, B) and reach fixation in LB5, while rpoS mutations (red) were more common in BHI-evolved populations (C, D).The frequencies represent the total frequencies of all arcA or respectively, identified in a particular population.
Mentions: The highly parallel evolution of mutations in arcA and rpoS combined with their global effects suggests that these mutations are driving adaptation in these complex selective environments. Mutations in these genes were very common with multiple different alleles co-occurring within the same population. The cumulative frequencies of arcA mutations in particular reached high frequencies in LB (average 0.75±0.08 (mean and 95%CI) across 24 populations (Fig. 6). In only one population did we observe the fixation of a single arcA mutation (LB5).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of BioSciences, Rice University, Houston, Texas, United States of America.

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.

Show MeSH
Related in: MedlinePlus