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

Gerda Saxer,Owen P Leiser,Charles Ansong,Nikola Ristic,Brooke L Deatherage Kaiser,Yousif Shamoo,Marie-Thérèse Valovska,Ping T Yeh,Luay Nakhleh,Vittal P Prakash,Michael D Krepps,Helen W Kreuzer,Eric D Merkley,Henry S Gibbons

doi:10.1371/journal.pgen.1004872

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.

Highlights

Adaptation to novel environments can proceed either through many mutations with small effects or through few mutations with large effects [1]
In addition to the populations selected in complex media, we performed a control experiment, where we reduced selection as much as possible by daily bottlenecking the population to a single cell, the approach commonly used for mutation accumulation (MA) experiments [43,44,45]
We used wild isolates of E. coli and C. freundii and investigated their adaptive responses under weak selection as they were moved from their natural habitat, the human gut, to a rich and markedly different resource base

Summary

Introduction

Adaptation to novel environments can proceed either through many mutations with small effects or through few mutations with large effects [1]. Ecological complexity can arise from increased species diversity, spatial or temporal heterogeneity or different resources. The availability of countless resources in complex environments can lead to a rapid and substantial increase in genetic diversity that can obscure broader biochemical principles of adaptation. Adaptation occurs through specialization via fitness improvements or via metabolic erosion possibly without fitness improvements relative to the ancestor [3,4,5]. Despite the tremendous opportunities for increased genetic diversity under conditions of plenty, consistent adaptive responses could be observed as parallel evolution across and within independently evolved populations.

Methods

Results

Conclusion