The impact of metabolism on the adaptation of organisms to environmental change

Abstract

Since Jacob and Monod’s discovery of the lac operon ∼1960, the explanations offered for most metabolic adaptations have been genetic. The focus has been on the adaptive changes in gene expression that occur, which are often referred to as “metabolic reprogramming.” The contributions metabolism makes to adaptation have been largely ignored. Here we point out that metabolic adaptations, including the associated changes in gene expression, are highly dependent on the metabolic state of an organism prior to the environmental change to which it is adapting, and on the plasticity of that state. In support of this hypothesis, we examine the paradigmatic example of a genetically driven adaptation, the adaptation of E. coli to growth on lactose, and the paradigmatic example of a metabolic driven adaptation, the Crabtree effect in yeast. Using a framework based on metabolic control analysis, we have reevaluated what is known about both adaptations, and conclude that knowledge of the metabolic properties of these organisms prior to environmental change is critical for understanding not only how they survive long enough to adapt, but also how the ensuing changes in gene expression occur, and their phenotypes post-adaptation. It would be useful if future explanations for metabolic adaptations acknowledged the contributions made to them by metabolism, and described the complex interplay between metabolic systems and genetic systems that make these adaptations possible.

Minimization of proteome reallocation explains metabolic transition in hierarchical utilization of carbon sources

“…We sequenced the genomes of the four evolved strains and found that the gene crr encoding glucose-specific phosphotransferase enzyme IIA component (EIIA Glc ) was mutated in all evolved strains (SI Appendix Table S4), in line with the findings that in various microbes the deletion of the gene crr diminished glucose repression on other carbon sources (47–49). In the presence of glucose, EIIA Glc is dephosphorylated which can inhibit transporters (50) and the genes involved in the catabolism of other carbon sources (51). By comparing the transcriptomics data between the strain Ev3 and the wildtype strain on the mixture of glucose and trehalose, we found many differentially expressed genes in the phosphotransferase system (SI Appendix Fig.…”

“…The biological basis of the minimization of proteome reallocation is the high cost and slow adjustment of protein synthesis and degradation 40, 48, 49 that the cells should consider when adapting to rapid perturbations. Additionally, the minimization of proteome reallocation is in line with the findings of proteome reserves 50, 51 , i.e., the proteome is not fully optimized for the environmental condition where the cells are living, as a suboptimal proteome could reduce the cost and time of reallocation upon the adaption to a new condition.…”

“…By integrating the minimization of proteome reallocation into the constraint-based modeling framework, we developed MORP and dMORP that introduce the past proteome as an internal constraint, which provide additional objective functions for simulating cellular behaviors 52 . Particularly, dMORP would serve as a promising algorithm in the field of dynamic metabolic modeling to predict cellular kinetics 53, 54 and history-dependent behaviors 48, 55, 56 .…”