Evolution of gene knockout strains of E. coli reveal regulatory architectures governed by metabolism

Douglas McCloskey, Sibei Xu, Troy E. Sandberg, Elizabeth Brunk, Ying Hefner, Richard Szubin, Adam M. Feist, Bernhard O. Palsson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Biological regulatory network architectures are multi-scale in their function and can adaptively acquire new functions. Gene knockout (KO) experiments provide an established experimental approach not just for studying gene function, but also for unraveling regulatory networks in which a gene and its gene product are involved. Here we study the regulatory architecture of Escherichia coli K-12 MG1655 by applying adaptive laboratory evolution (ALE) to metabolic gene KO strains. Multi-omic analysis reveal a common overall schema describing the process of adaptation whereby perturbations in metabolite concentrations lead regulatory networks to produce suboptimal states, whose function is subsequently altered and re-optimized through acquisition of mutations during ALE. These results indicate that metabolite levels, through metabolite-transcription factor interactions, have a dominant role in determining the function of a multi-scale regulatory architecture that has been molded by evolution.

Original languageEnglish
Article number3796
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Bibliographical note

Funding Information:
We thank José Utrilla for helpful discussion and guidance when implementing the knockouts in the pre-evolved strain. We thank Jamey Young for helpful discussions throughout the MFA analysis. We thank Laurence Yang for helpful discussions regarding optimization and statistical analysis. This work was funded by the Novo Nordisk Foundation Grant Number NNF10CC1016517.

Publisher Copyright:
© 2018, The Author(s).

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