Regulatory network structure determines patterns of intermolecular epistasis Journal Article

Author(s): Lagator, Mato; Sarikas, Srdjan; Acar, Hande; Bollback, Jonathan P; Guet, Cǎlin C
Article Title: Regulatory network structure determines patterns of intermolecular epistasis
Affiliation IST Austria
Abstract: Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution.
Journal Title: eLife
Volume: 6
ISSN: 2050-084X
Publisher: eLife Sciences Publications  
Date Published: 2017-11-13
Start Page: Article number: e28921
Copyright Statement: CC BY
Sponsor: This work was supported by the People Programme (Marie Curie Actions) of the European Union FP7/2007-2013 grant agreement no. 291734 to ML and ERC H2020 Programme Consolidator Grant no. 648440 to JPB
DOI: 10.7554/eLife.28921
Notes: We thank N Barton, T Bergmiller, A Betancourt, K Bodova, C Igler, C Nizak, T Paixao, M Pleska, D Siekhaus, M Steinrueck, and G Tkacik for their invaluable comments on the manuscript.
Open access: yes (OA journal)