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 language | English |
|---|---|
| Article number | 3796 |
| Journal | Nature Communications |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 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).