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