Adaptive evolution reveals a tradeoff between growth rate and oxidative stress during naphthoquinone-based aerobic respiration

Abstract

Evolution fine-tunes biological pathways to achieve a robust cellular physiology. Two and a half billion years ago, rapidly rising levels of oxygen as a byproduct of blooming cyanobacterial photosynthesis resulted in a redox upshift in microbial energetics. The appearance of higher-redox-potential respiratory quinone, ubiquinone (UQ), is believed to be an adaptive response to this environmental transition. However, the majority of bacterial species are still dependent on the ancient respiratory quinone, naphthoquinone (NQ). Gammaproteobacteria can biosynthesize both of these respiratory quinones, where UQ has been associated with aerobic lifestyle and NQ with anaerobic lifestyle. We engineered an obligate NQ-dependent γ-proteobacterium, Escherichia coli ΔubiC, and performed adaptive laboratory evolution to understand the selection against the use of NQ in an oxic environment and also the adaptation required to support the NQ-driven aerobic electron transport chain. A comparative systems-level analysis of pre- and postevolved NQ-dependent strains revealed a clear shift from fermentative to oxidative metabolism enabled by higher periplasmic superoxide defense. This metabolic shift was driven by the concerted activity of 3 transcriptional regulators (PdhR, RpoS, and Fur). Analysis of these findings using a genome-scale model suggested that resource allocation to reactive oxygen species (ROS) mitigation results in lower growth rates. These results provide a direct elucidation of a resource allocation tradeoff between growth rate and ROS mitigation costs associated with NQ usage under oxygen-replete condition.

Changes in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation

“…1 ststep adapted mutants had either RAS/PKA or TOR/Sch9 pathway upregulated 4,20 , which may decrease stress responses compared to their ancestor [56][57][58][59][60][61][62][63][64][65][66] . The adaptive basis of 2 nd -step mutations may lie in the restoration of stress responses attenuated by overactive RAS/PKA or TOR/Sch9 pathways, as suggested by prior work 51,[57][58][59][60][61][62][63][64][65][66] . In particular, all adapted ancestors evolved in this study acquired mutations in the GSH1 gene, and evidence suggests that these mutations are gain-of-function, possibly resulting in an enhanced stress response.…”

Revealing 29 sets of independently modulated genes inStaphylococcus aureus, their regulators and role in key physiological responses

“…However, beyond regulons, i-modulons can also describe other genomic features, such as strain differences and genetic alterations (e.g. gene knock-out) that can lead to change in gene co-expression 9,11 . The outcome of this approach is a biologically relevant, low dimensional mathematical representation of functional modules in the TRN that reconstruct most of the information content of the input RNAseq compendium ( Figure S1b ).…”

“…ICA analysis of expression profiles in E. coli have been used to describe undefined regulons, link strain-specific mutations with changes in gene expression, and understand rewiring of TRN during Adaptive Laboratory Evolution (ALE) 7,9 . Given the deeper insights it provided into the TRN of E. coli , we sought to expand this approach to the human pathogen S. aureus .…”

Debating Eukaryogenesis—Part 2: How Anachronistic Reasoning Can Lure Us into Inventing Intermediates

“…In a recent, beautiful paper Anand and co‐workers report on the creation of E.coli that has to make do with NQ only. [ 28 ] This knock‐out has a reduced growth rate, less O 2 uptake and secretes lactate because of higher rates of fermentation. However, upon further adaptive evolution in the laboratory, growth rate, oxygen uptake, and lactate secretion return to wild type patterns; however, not completely.…”