Epistatic interactions in the arabinose cis-regulatory element Journal Article

Author(s): Lagator, Mato; Igler, Claudia; Moreno, Anaisa B; Guet, Cǎlin C; Bollback, Jonathan P
Article Title: Epistatic interactions in the arabinose cis-regulatory element
Affiliation IST Austria
Abstract: Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner.
Keywords: Gene Expression; Epistasis; gene regulation; cis-regulatory elements
Journal Title: Molecular Biology and Evolution
Volume: 33
Issue 3
ISSN: 0737-4038
Publisher: OUP  
Date Published: 2016-03-01
Start Page: 761
End Page: 769
Copyright Statement: CC BY 4.0
DOI: 10.1093/molbev/msv269
Notes: We would like to thank Madhumitha Narasimhan for her help in constructing the plasmid backbone, Andrea Betancourt for providing insi ghtful comments on the manu- script, as well as Hande Acar, Fabienne Jesse, Tobias Bergmiller, Tiago Paixao, and anonymous reviewers for helpful discussions. This work was supported by the People Programme (Marie Curie Acti ons) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 291734.
Open access: yes (OA journal)