{"department":[{"_id":"CaGu"},{"_id":"JoBo"},{"_id":"NiBa"}],"oa_version":"Published Version","date_published":"2017-11-13T00:00:00Z","ec_funded":1,"abstract":[{"text":"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. ","lang":"eng"}],"oa":1,"publist_id":"7244","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publisher":"eLife Sciences Publications","article_number":"e28921","file":[{"relation":"main_file","file_name":"IST-2017-918-v1+1_elife-28921-figures-v3.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:47:10Z","date_created":"2018-12-12T10:14:42Z","file_size":8453470,"creator":"system","checksum":"273ab17f33305e4eaafd911ff88e7c5b","access_level":"open_access","file_id":"5096"},{"date_created":"2018-12-12T10:14:43Z","file_size":1953221,"date_updated":"2020-07-14T12:47:10Z","creator":"system","checksum":"b433f90576c7be597cd43367946f8e7f","relation":"main_file","file_name":"IST-2017-918-v1+2_elife-28921-v3.pdf","content_type":"application/pdf","file_id":"5097","access_level":"open_access"}],"day":"13","intvolume":"         6","project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"language":[{"iso":"eng"}],"date_created":"2018-12-11T11:47:14Z","publication_identifier":{"issn":["2050084X"]},"pubrep_id":"918","file_date_updated":"2020-07-14T12:47:10Z","title":"Regulatory network structure determines patterns of intermolecular epistasis","status":"public","publication_status":"published","citation":{"ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","mla":"Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” <i>ELife</i>, vol. 6, e28921, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.28921\">10.7554/eLife.28921</a>.","ama":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure determines patterns of intermolecular epistasis. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.28921\">10.7554/eLife.28921</a>","chicago":"Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.28921\">https://doi.org/10.7554/eLife.28921</a>.","apa":"Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., &#38; Guet, C. C. (2017). Regulatory network structure determines patterns of intermolecular epistasis. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.28921\">https://doi.org/10.7554/eLife.28921</a>","ieee":"M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","short":"M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017)."},"month":"11","publication":"eLife","scopus_import":1,"ddc":["576"],"volume":6,"_id":"570","year":"2017","quality_controlled":"1","doi":"10.7554/eLife.28921","has_accepted_license":"1","date_updated":"2021-01-12T08:03:15Z","author":[{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato"},{"id":"35F0286E-F248-11E8-B48F-1D18A9856A87","last_name":"Sarikas","first_name":"Srdjan","full_name":"Sarikas, Srdjan"},{"first_name":"Hande","id":"2DDF136A-F248-11E8-B48F-1D18A9856A87","last_name":"Acar","orcid":"0000-0003-1986-9753","full_name":"Acar, Hande"},{"last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","full_name":"Bollback, Jonathan P"},{"first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"}