Laboratory evolution of multipleE. colistrains reveals unifying principles of adaptation but diversity in driving genotypes

Abstract

Fitness landscapes are a central concept in evolutionary biology and have been thoroughly detailed in terms of genotypes. However, our understanding of the selected metabolic and gene expression adaptations, and their dependence on genetic background, remains limited. Here, we reveal multi-scale adaptation principles in the E. coli species by taking multi-omics measurements of six different strains throughout their adaptive evolution to glucose minimal media. Statistics and matrix factorization is applied to yield four key results. First, analysis of the metabolic and physiological data shows evolutionary convergence in growth rate, glucose uptake rate, glycolytic ATP and NADH production but divergence in NADPH production strategies. Second, factorization-based analysis of the transcriptome revealed six conserved transcriptomic adaptations describing increased expression of ribosome and amino acid biosynthetic genes and decreased expression of stress response and structural genes. Third, correlation analysis identifies five tradeoffs underlying the transcriptomic profiles. Fourth, statistical tests leveraging ALE design identify four mutation-flux correlates and eight mutation-transcriptomic correlates that link mutations to systems level adaptation principles. Our total results reveal the dominant metabolic and regulatory constraints governing E. coli growth adaptation that either distinguish strains or are conserved principles.

Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications

“…There is a fear-greed trade-off that fulfills the growth objective of a cell by shifting metabolic resources toward growth-related functions and away from stress-defense functions (Utrilla et al, 2016). We observed an unexpected trend in the translation All DIMA plots (Kavvas et al, 2020;Sastry et al, 2019) have the same scale on the x and y axes, which can be seen in the example plot. DpdhR-evolved replicates showed a high positive correlation among themselves and with the media-adapted GMOS strain, but the transcriptome was poorly correlated with DpdhR or the unevolved WT strain.…”

“… All DIMA plots ( Kavvas et al, 2020 ; Sastry et al, 2019 ) have the same scale on the x and y axes, which can be seen in the example plot. Δ pdhR -evolved replicates showed a high positive correlation among themselves and with the media-adapted GMOS strain, but the transcriptome was poorly correlated with Δ pdhR or the unevolved WT strain.…”

Random Chromosomal Integration and Screening Yields E. coli K-12 Derivatives Capable of Efficient Sucrose Utilization

“…Accordingly, we made use of three E. coli K-12 derivative strains previously generated through ALE, a strategy that relieved growth rate limitations considerably . Each strain (ALE-1, ALE-2, and ALE-3) represents evolved end-point clones of the E.…”

An automated DIY framework for experimental evolution of Pseudomonas putida

“…The emergence of this modification acted in fact as a descriptor of the efficacy of the evolutionary experiment. This is because as a large number of rpoC mutations have been reported in the course of laboratory evolution studies aiming to increase E. coli growth rate (Cheng et al, 2014;Wytock et al, 2018;Kavvas et al, 2020) (Davis and Henderson, 1987), and Gly 33 is located in a periplasmic side close to the H + coupling site Asp 27 (Madej et al, 2014). While a number of lossof-function mutations have been reported for xylE (Sun et al, 2012), to the best of our knowledge no changes are known to enhance xylose transport.…”

“…The emergence of this modification acted in fact as a descriptor of the efficacy of the evolutionary experiment. This is because as a large number of rpoC mutations have been reported in the course of laboratory evolution studies aiming to increase E. coli growth rate (Cheng et al ., 2014 ; Wytock et al ., 2018 ; Kavvas et al ., 2020 ). Therefore, the Pro 51 Leu change plausibly reflects a similar adaptation in P. putida .…”