--- res: bibo_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. @eng bibo_authorlist: - foaf_Person: foaf_givenName: Mato foaf_name: Lagator, Mato foaf_surname: Lagator foaf_workInfoHomepage: http://www.librecat.org/personId=345D25EC-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Srdjan foaf_name: Sarikas, Srdjan foaf_surname: Sarikas foaf_workInfoHomepage: http://www.librecat.org/personId=35F0286E-F248-11E8-B48F-1D18A9856A87 - foaf_Person: foaf_givenName: Hande foaf_name: Acar, Hande foaf_surname: Acar foaf_workInfoHomepage: http://www.librecat.org/personId=2DDF136A-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0003-1986-9753 - foaf_Person: foaf_givenName: Jonathan P foaf_name: Bollback, Jonathan P foaf_surname: Bollback foaf_workInfoHomepage: http://www.librecat.org/personId=2C6FA9CC-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-4624-4612 - foaf_Person: foaf_givenName: Calin C foaf_name: Guet, Calin C foaf_surname: Guet foaf_workInfoHomepage: http://www.librecat.org/personId=47F8433E-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0001-6220-2052 bibo_doi: 10.7554/eLife.28921 bibo_volume: 6 dct_date: 2017^xs_gYear dct_isPartOf: - http://id.crossref.org/issn/2050084X dct_language: eng dct_publisher: eLife Sciences Publications@ dct_title: Regulatory network structure determines patterns of intermolecular epistasis@ ...