Global Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution.

TitleGlobal Rebalancing of Cellular Resources by Pleiotropic Point Mutations Illustrates a Multi-scale Mechanism of Adaptive Evolution.
Publication TypeJournal Article
Year of Publication2016
AuthorsUtrilla J, O'Brien EJ, Chen K, McCloskey D, Cheung J, Wang H, Armenta-Medina D, Feist AM, Palsson BO
JournalCell Syst
Volume2
Issue4
Pagination260-71
Date Published2016 Apr 27
ISSN2405-4712
Abstract

Pleiotropic regulatory mutations affect diverse cellular processes, posing a challenge to our understanding of genotype-phenotype relationships across multiple biological scales. Adaptive laboratory evolution (ALE) allows for such mutations to be found and characterized in the context of clear selection pressures. Here, several ALE-selected single-mutation variants in RNA polymerase (RNAP) of Escherichia coli are detailed using an integrated multi-scale experimental and computational approach. While these mutations increase cellular growth rates in steady environments, they reduce tolerance to stress and environmental fluctuations. We detail structural changes in the RNAP that rewire the transcriptional machinery to rebalance proteome and energy allocation toward growth and away from several hedging and stress functions. We find that while these mutations occur in diverse locations in the RNAP, they share a common adaptive mechanism. In turn, these findings highlight the resource allocation trade-offs organisms face and suggest how the structure of the regulatory network enhances evolvability.

DOI10.1016/j.cels.2016.04.003
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/27135538?dopt=Abstract
Alternate JournalCell Syst
PubMed ID27135538
PubMed Central IDPMC4853925
Grant ListR01 GM057089 / GM / NIGMS NIH HHS / United States
Track(s): 
Bioinformatics and Systems Biology