Epistatic interactions in the arabinose cis-regulatory element

Lagator, Mato and Igler, Claudia and Moreno, Anaisa B and Guet, Cǎlin C and Bollback, Jonathan P (2016) Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution, 33 (3). pp. 761-769. ISSN 0737-4038

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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.

Item Type: Article
DOI: 10.1093/molbev/msv269
Uncontrolled Keywords: Gene Expression, Epistasis, gene regulation, cis-regulatory elements
Subjects: 500 Science > 570 Life sciences; biology
500 Science > 570 Life sciences; biology > 576 Genetics and evolution
Research Group: Bollback Group
Guet Group
SWORD Depositor: Sword Import User
Depositing User: Sword Import User
Date Deposited: 25 May 2016 14:27
Last Modified: 05 Sep 2017 09:21
URI: https://repository.ist.ac.at/id/eprint/588

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