[{"type":"journal_article","abstract":[{"text":"Predicting function from sequence is a central problem of biology. Currently, this is possible only locally in a narrow mutational neighborhood around a wildtype sequence rather than globally from any sequence. Using random mutant libraries, we developed a biophysical model that accounts for multiple features of σ70 binding bacterial promoters to predict constitutive gene expression levels from any sequence. We experimentally and theoretically estimated that 10–20% of random sequences lead to expression and ~80% of non-expressing sequences are one mutation away from a functional promoter. The potential for generating expression from random sequences is so pervasive that selection acts against σ70-RNA polymerase binding sites even within inter-genic, promoter-containing regions. This pervasiveness of σ70-binding sites implies that emergence of promoters is not the limiting step in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter function into a mechanistic model enabled not only more accurate predictions of gene expression levels, but also identified that promoters evolve more rapidly than previously thought.","lang":"eng"}],"title":"Predicting bacterial promoter function and evolution from random sequences","status":"public","ddc":["576"],"intvolume":" 11","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10736","file":[{"file_name":"2022_ELife_Lagator.pdf","access_level":"open_access","content_type":"application/pdf","file_size":5604343,"creator":"cchlebak","relation":"main_file","file_id":"10739","date_updated":"2022-02-07T07:14:09Z","date_created":"2022-02-07T07:14:09Z","checksum":"decdcdf600ff51e9a9703b49ca114170","success":1}],"oa_version":"Published Version","scopus_import":"1","day":"26","article_processing_charge":"No","has_accepted_license":"1","article_type":"original","publication":"eLife","citation":{"chicago":"Lagator, Mato, Srdjan Sarikas, Magdalena Steinrueck, David Toledo-Aparicio, Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/eLife.64543.","short":"M. Lagator, S. Sarikas, M. Steinrueck, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022).","mla":"Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” ELife, vol. 11, e64543, eLife Sciences Publications, 2022, doi:10.7554/eLife.64543.","apa":"Lagator, M., Sarikas, S., Steinrueck, M., Toledo-Aparicio, D., Bollback, J. P., Guet, C. C., & Tkačik, G. (2022). Predicting bacterial promoter function and evolution from random sequences. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.64543","ieee":"M. Lagator et al., “Predicting bacterial promoter function and evolution from random sequences,” eLife, vol. 11. eLife Sciences Publications, 2022.","ista":"Lagator M, Sarikas S, Steinrueck M, Toledo-Aparicio D, Bollback JP, Guet CC, Tkačik G. 2022. Predicting bacterial promoter function and evolution from random sequences. eLife. 11, e64543.","ama":"Lagator M, Sarikas S, Steinrueck M, et al. Predicting bacterial promoter function and evolution from random sequences. eLife. 2022;11. doi:10.7554/eLife.64543"},"date_published":"2022-01-26T00:00:00Z","article_number":"e64543","license":"https://creativecommons.org/licenses/by/4.0/","file_date_updated":"2022-02-07T07:14:09Z","ec_funded":1,"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"acknowledgement":"We thank Hande Acar, Nicholas H Barton, Rok Grah, Tiago Paixao, Maros Pleska, Anna Staron, and Murat Tugrul for insightful comments and input on the manuscript. This work was supported by: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 216779/Z/19/Z) to ML; IPC Grant from IST Austria to ML and SS; European Research Council Funding Programme 7 (2007–2013, grant agreement number 648440) to JPB.","year":"2022","pmid":1,"date_updated":"2023-08-02T14:09:02Z","date_created":"2022-02-06T23:01:32Z","volume":11,"author":[{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato"},{"first_name":"Srdjan","last_name":"Sarikas","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","full_name":"Sarikas, Srdjan"},{"full_name":"Steinrueck, Magdalena","last_name":"Steinrueck","first_name":"Magdalena"},{"full_name":"Toledo-Aparicio, David","first_name":"David","last_name":"Toledo-Aparicio"},{"last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"first_name":"Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper"}],"month":"01","publication_identifier":{"eissn":["2050-084X"]},"quality_controlled":"1","isi":1,"project":[{"name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020","grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425"}],"external_id":{"isi":["000751104400001"],"pmid":["35080492"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.7554/eLife.64543"},{"publication_identifier":{"eissn":["1744957X"]},"month":"05","language":[{"iso":"eng"}],"doi":"10.1098/rsbl.2020.0913","project":[{"_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152","call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation"}],"quality_controlled":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"pmid":[" 33975485"],"isi":["000651501400001"]},"ec_funded":1,"file_date_updated":"2021-05-25T14:09:03Z","article_number":"20200913","volume":17,"date_updated":"2023-08-08T13:44:35Z","date_created":"2021-05-23T22:01:43Z","author":[{"first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"full_name":"Uecker, Hildegard","id":"2DB8F68A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9435-2813","first_name":"Hildegard","last_name":"Uecker"},{"last_name":"Neve","first_name":"Paul","full_name":"Neve, Paul"}],"publisher":"Royal Society of London","department":[{"_id":"NiBa"}],"publication_status":"published","pmid":1,"acknowledgement":"We would like to thank Martin Ackermann, Camilo Barbosa, Nick Barton, Jonathan Bollback, Sebastian Bonhoeffer, Nick Colegrave, Calin Guet, Alex Hall, Sally Otto, Tiago Paixao, Srdjan Sarikas, Hinrich Schulenburg, Marjon de Vos and Michael Whitlock for insightful support.","year":"2021","article_processing_charge":"No","has_accepted_license":"1","day":"12","scopus_import":"1","date_published":"2021-05-12T00:00:00Z","citation":{"chicago":"Lagator, Mato, Hildegard Uecker, and Paul Neve. “Adaptation at Different Points along Antibiotic Concentration Gradients.” Biology Letters. Royal Society of London, 2021. https://doi.org/10.1098/rsbl.2020.0913.","short":"M. Lagator, H. Uecker, P. Neve, Biology Letters 17 (2021).","mla":"Lagator, Mato, et al. “Adaptation at Different Points along Antibiotic Concentration Gradients.” Biology Letters, vol. 17, no. 5, 20200913, Royal Society of London, 2021, doi:10.1098/rsbl.2020.0913.","ieee":"M. Lagator, H. Uecker, and P. Neve, “Adaptation at different points along antibiotic concentration gradients,” Biology letters, vol. 17, no. 5. Royal Society of London, 2021.","apa":"Lagator, M., Uecker, H., & Neve, P. (2021). Adaptation at different points along antibiotic concentration gradients. Biology Letters. Royal Society of London. https://doi.org/10.1098/rsbl.2020.0913","ista":"Lagator M, Uecker H, Neve P. 2021. Adaptation at different points along antibiotic concentration gradients. Biology letters. 17(5), 20200913.","ama":"Lagator M, Uecker H, Neve P. Adaptation at different points along antibiotic concentration gradients. Biology letters. 2021;17(5). doi:10.1098/rsbl.2020.0913"},"publication":"Biology letters","issue":"5","abstract":[{"text":"Antibiotic concentrations vary dramatically in the body and the environment. Hence, understanding the dynamics of resistance evolution along antibiotic concentration gradients is critical for predicting and slowing the emergence and spread of resistance. While it has been shown that increasing the concentration of an antibiotic slows resistance evolution, how adaptation to one antibiotic concentration correlates with fitness at other points along the gradient has not received much attention. Here, we selected populations of Escherichia coli at several points along a concentration gradient for three different antibiotics, asking how rapidly resistance evolved and whether populations became specialized to the antibiotic concentration they were selected on. Populations selected at higher concentrations evolved resistance more slowly but exhibited equal or higher fitness across the whole gradient. Populations selected at lower concentrations evolved resistance rapidly, but overall fitness in the presence of antibiotics was lower. However, these populations readily adapted to higher concentrations upon subsequent selection. Our results indicate that resistance management strategies must account not only for the rates of resistance evolution but also for the fitness of evolved strains.","lang":"eng"}],"type":"journal_article","file":[{"date_updated":"2021-05-25T14:09:03Z","date_created":"2021-05-25T14:09:03Z","success":1,"checksum":"9c13c1f5af7609c97c741f11d293188a","file_id":"9425","relation":"main_file","creator":"kschuh","file_size":726759,"content_type":"application/pdf","file_name":"2021_BiologyLetters_Lagator.pdf","access_level":"open_access"}],"oa_version":"Published Version","intvolume":" 17","ddc":["570"],"title":"Adaptation at different points along antibiotic concentration gradients","status":"public","_id":"9410","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"oa_version":"Submitted Version","file":[{"date_created":"2020-05-14T11:28:52Z","date_updated":"2020-07-14T12:47:37Z","checksum":"383a2e2c944a856e2e821ec8e7bf71b6","file_id":"7830","relation":"main_file","creator":"dernst","file_size":1135973,"content_type":"application/pdf","file_name":"2018_NatureEcology_Igler.pdf","access_level":"open_access"}],"title":"Evolutionary potential of transcription factors for gene regulatory rewiring","status":"public","ddc":["570"],"intvolume":" 2","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"67","abstract":[{"text":"Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution.","lang":"eng"}],"issue":"10","type":"journal_article","date_published":"2018-09-10T00:00:00Z","article_type":"original","page":"1633 - 1643","publication":"Nature Ecology and Evolution","citation":{"ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2018;2(10):1633-1643. doi:10.1038/s41559-018-0651-y","ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary potential of transcription factors for gene regulatory rewiring,” Nature Ecology and Evolution, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018.","apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018). Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. Nature Publishing Group. https://doi.org/10.1038/s41559-018-0651-y","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2(10), 1633–1643.","short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology and Evolution 2 (2018) 1633–1643.","mla":"Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution, vol. 2, no. 10, Nature Publishing Group, 2018, pp. 1633–43, doi:10.1038/s41559-018-0651-y.","chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Nature Ecology and Evolution. Nature Publishing Group, 2018. https://doi.org/10.1038/s41559-018-0651-y."},"day":"10","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","date_updated":"2024-03-28T23:30:49Z","date_created":"2018-12-11T11:44:27Z","volume":2,"author":[{"full_name":"Igler, Claudia","first_name":"Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lagator, Mato","last_name":"Lagator","first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tkacik, Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkacik","first_name":"Gasper"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","last_name":"Bollback","full_name":"Bollback, Jonathan P"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"related_material":{"record":[{"relation":"popular_science","status":"public","id":"5585"},{"relation":"dissertation_contains","status":"public","id":"6371"}]},"publication_status":"published","publisher":"Nature Publishing Group","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"JoBo"}],"year":"2018","file_date_updated":"2020-07-14T12:47:37Z","ec_funded":1,"publist_id":"7987","language":[{"iso":"eng"}],"doi":"10.1038/s41559-018-0651-y","quality_controlled":"1","isi":1,"project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440"},{"grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)"}],"external_id":{"isi":["000447947600021"]},"oa":1,"month":"09"},{"datarep_id":"108","type":"research_data","license":"https://creativecommons.org/publicdomain/zero/1.0/","file_date_updated":"2020-07-14T12:47:07Z","abstract":[{"text":"Mean repression values and standard error of the mean are given for all operator mutant libraries.","lang":"eng"}],"ec_funded":1,"title":"Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring","status":"public","ddc":["576"],"publisher":"Institute of Science and Technology Austria","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"_id":"5585","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2018","date_created":"2018-12-12T12:31:40Z","date_updated":"2024-03-28T23:30:49Z","file":[{"date_updated":"2020-07-14T12:47:07Z","date_created":"2018-12-12T13:02:45Z","checksum":"1435781526c77413802adee0d4583cce","relation":"main_file","file_id":"5611","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","file_size":16507,"creator":"system","file_name":"IST-2018-108-v1+1_data_figures.xlsx","access_level":"open_access"}],"oa_version":"Published Version","author":[{"full_name":"Igler, Claudia","last_name":"Igler","first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato"},{"full_name":"Tkacik, Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gasper","last_name":"Tkacik"},{"last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"related_material":{"record":[{"id":"67","relation":"research_paper","status":"public"},{"id":"6371","status":"public","relation":"research_paper"}]},"day":"20","month":"07","article_processing_charge":"No","has_accepted_license":"1","project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer"},{"name":"Design principles underlying genetic switch architecture (DOC Fellowship)","_id":"251EE76E-B435-11E9-9278-68D0E5697425","grant_number":"24573"}],"citation":{"chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:108.","short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, (2018).","mla":"Igler, Claudia, et al. Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:108.","ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring.” Institute of Science and Technology Austria, 2018.","apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., & Guet, C. C. (2018). Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:108","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring, Institute of Science and Technology Austria, 10.15479/AT:ISTA:108.","ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. 2018. doi:10.15479/AT:ISTA:108"},"tmp":{"short":"CC0 (1.0)","image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)"},"oa":1,"doi":"10.15479/AT:ISTA:108","date_published":"2018-07-20T00:00:00Z"},{"author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"id":"35F0286E-F248-11E8-B48F-1D18A9856A87","first_name":"Srdjan","last_name":"Sarikas","full_name":"Sarikas, Srdjan"},{"orcid":"0000-0003-1986-9753","id":"2DDF136A-F248-11E8-B48F-1D18A9856A87","last_name":"Acar","first_name":"Hande","full_name":"Acar, Hande"},{"full_name":"Bollback, Jonathan P","last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"}],"date_created":"2018-12-11T11:47:14Z","date_updated":"2021-01-12T08:03:15Z","volume":6,"year":"2017","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"JoBo"},{"_id":"NiBa"}],"publisher":"eLife Sciences Publications","file_date_updated":"2020-07-14T12:47:10Z","publist_id":"7244","ec_funded":1,"article_number":"e28921","doi":"10.7554/eLife.28921","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"quality_controlled":"1","project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer"}],"month":"11","publication_identifier":{"issn":["2050084X"]},"pubrep_id":"918","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"5096","date_updated":"2020-07-14T12:47:10Z","date_created":"2018-12-12T10:14:42Z","checksum":"273ab17f33305e4eaafd911ff88e7c5b","file_name":"IST-2017-918-v1+1_elife-28921-figures-v3.pdf","access_level":"open_access","file_size":8453470,"content_type":"application/pdf","creator":"system"},{"relation":"main_file","file_id":"5097","checksum":"b433f90576c7be597cd43367946f8e7f","date_updated":"2020-07-14T12:47:10Z","date_created":"2018-12-12T10:14:43Z","access_level":"open_access","file_name":"IST-2017-918-v1+2_elife-28921-v3.pdf","content_type":"application/pdf","file_size":1953221,"creator":"system"}],"_id":"570","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Regulatory network structure determines patterns of intermolecular epistasis","ddc":["576"],"status":"public","intvolume":" 6","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"}],"type":"journal_article","date_published":"2017-11-13T00:00:00Z","publication":"eLife","citation":{"chicago":"Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.28921.","short":"M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017).","mla":"Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife, vol. 6, e28921, eLife Sciences Publications, 2017, doi:10.7554/eLife.28921.","apa":"Lagator, M., Sarikas, S., Acar, H., Bollback, J. P., & Guet, C. C. (2017). Regulatory network structure determines patterns of intermolecular epistasis. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.28921","ieee":"M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” eLife, vol. 6. eLife Sciences Publications, 2017.","ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","ama":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 2017;6. doi:10.7554/eLife.28921"},"day":"13","has_accepted_license":"1","scopus_import":1},{"abstract":[{"text":"Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","file":[{"creator":"system","file_size":2441529,"content_type":"application/pdf","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf","access_level":"open_access","date_created":"2018-12-12T10:17:49Z","date_updated":"2020-07-14T12:48:16Z","checksum":"59cdd4400fb41280122d414fea971546","file_id":"5306","relation":"main_file"},{"file_id":"5307","relation":"main_file","date_updated":"2020-07-14T12:48:16Z","date_created":"2018-12-12T10:17:50Z","checksum":"b69024880558b858eb8c5d47a92b6377","file_name":"IST-2017-841-v1+2_elife-25192-figures-v2.pdf","access_level":"open_access","creator":"system","content_type":"application/pdf","file_size":3752660}],"pubrep_id":"841","intvolume":" 6","status":"public","title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","ddc":["576"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"954","article_processing_charge":"Yes","has_accepted_license":"1","day":"18","scopus_import":"1","date_published":"2017-05-18T00:00:00Z","citation":{"chicago":"Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192.","mla":"Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife, vol. 6, e25192, eLife Sciences Publications, 2017, doi:10.7554/eLife.25192.","short":"M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017).","ista":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192.","ieee":"M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the mechanistic nature of epistasis in a canonical cis-regulatory element,” eLife, vol. 6. eLife Sciences Publications, 2017.","apa":"Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192","ama":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 2017;6. doi:10.7554/eLife.25192"},"publication":"eLife","publist_id":"6460","ec_funded":1,"file_date_updated":"2020-07-14T12:48:16Z","article_number":"e25192","volume":6,"date_created":"2018-12-11T11:49:23Z","date_updated":"2023-09-22T10:01:17Z","author":[{"last_name":"Lagator","first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago"},{"first_name":"Nicholas H","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H"},{"last_name":"Bollback","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P"},{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"publisher":"eLife Sciences Publications","publication_status":"published","year":"2017","publication_identifier":{"issn":["2050084X"]},"month":"05","language":[{"iso":"eng"}],"doi":"10.7554/eLife.25192","project":[{"grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","call_identifier":"FP7"},{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020"}],"isi":1,"quality_controlled":"1","external_id":{"isi":["000404024800001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1},{"file_date_updated":"2020-07-14T12:44:53Z","ec_funded":1,"publist_id":"5772","date_updated":"2021-01-12T06:50:39Z","date_created":"2018-12-11T11:51:57Z","volume":33,"author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato","full_name":"Lagator, Mato"},{"full_name":"Igler, Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","last_name":"Igler","first_name":"Claudia"},{"full_name":"Moreno, Anaisa","last_name":"Moreno","first_name":"Anaisa"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C"},{"full_name":"Bollback, Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","last_name":"Bollback"}],"publication_status":"published","department":[{"_id":"CaGu"},{"_id":"JoBo"}],"publisher":"Oxford University Press","year":"2016","month":"03","language":[{"iso":"eng"}],"doi":"10.1093/molbev/msv269","quality_controlled":"1","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"abstract":[{"lang":"eng","text":"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."}],"issue":"3","type":"journal_article","oa_version":"Published Version","file":[{"checksum":"1f456ce1d2aa2f67176a1709f9702ecf","date_updated":"2020-07-14T12:44:53Z","date_created":"2018-12-12T10:09:27Z","file_id":"4751","relation":"main_file","creator":"system","file_size":648115,"content_type":"application/pdf","access_level":"open_access","file_name":"IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf"}],"pubrep_id":"588","title":"Epistatic interactions in the arabinose cis-regulatory element","status":"public","ddc":["570","576"],"intvolume":" 33","_id":"1427","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","day":"01","has_accepted_license":"1","scopus_import":1,"date_published":"2016-03-01T00:00:00Z","page":"761 - 769","publication":"Molecular Biology and Evolution","citation":{"ista":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3), 761–769.","apa":"Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016). Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269","ieee":"M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic interactions in the arabinose cis-regulatory element,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016.","ama":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 2016;33(3):761-769. doi:10.1093/molbev/msv269","chicago":"Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269.","mla":"Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269.","short":"M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769."}},{"publist_id":"4954","file_date_updated":"2020-07-14T12:45:28Z","related_material":{"record":[{"id":"9747","status":"public","relation":"research_data"}]},"author":[{"full_name":"Lagator, Mato","first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Andrew","last_name":"Morgan","full_name":"Morgan, Andrew"},{"full_name":"Neve, Paul","first_name":"Paul","last_name":"Neve"},{"first_name":"Nick","last_name":"Colegrave","full_name":"Colegrave, Nick"}],"volume":68,"date_created":"2018-12-11T11:55:36Z","date_updated":"2023-02-23T14:06:51Z","year":"2014","acknowledgement":"The authors are grateful to the Leverhulme Trust (F/00 215/AW) for funding this work.","department":[{"_id":"CaGu"}],"publisher":"Wiley","publication_status":"published","month":"04","doi":"10.1111/evo.12440","language":[{"iso":"eng"}],"oa":1,"quality_controlled":"1","issue":"8","abstract":[{"lang":"eng","text":"Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment."}],"type":"journal_article","oa_version":"Published Version","file":[{"file_name":"2014_Evolution_Lagator.pdf","access_level":"open_access","creator":"dernst","file_size":467254,"content_type":"application/pdf","file_id":"7845","relation":"main_file","date_created":"2020-05-14T16:40:31Z","date_updated":"2020-07-14T12:45:28Z","checksum":"8d459b07e4a11bb5fde92d969184fe48"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"2083","intvolume":" 68","title":"Role of sex and migration in adaptation to sink environments","status":"public","ddc":["570"],"article_processing_charge":"No","has_accepted_license":"1","day":"25","scopus_import":1,"date_published":"2014-04-25T00:00:00Z","citation":{"mla":"Lagator, Mato, et al. “Role of Sex and Migration in Adaptation to Sink Environments.” Evolution, vol. 68, no. 8, Wiley, 2014, pp. 2296–305, doi:10.1111/evo.12440.","short":"M. Lagator, A. Morgan, P. Neve, N. Colegrave, Evolution 68 (2014) 2296–2305.","chicago":"Lagator, Mato, Andrew Morgan, Paul Neve, and Nick Colegrave. “Role of Sex and Migration in Adaptation to Sink Environments.” Evolution. Wiley, 2014. https://doi.org/10.1111/evo.12440.","ama":"Lagator M, Morgan A, Neve P, Colegrave N. Role of sex and migration in adaptation to sink environments. Evolution. 2014;68(8):2296-2305. doi:10.1111/evo.12440","ista":"Lagator M, Morgan A, Neve P, Colegrave N. 2014. Role of sex and migration in adaptation to sink environments. Evolution. 68(8), 2296–2305.","ieee":"M. Lagator, A. Morgan, P. Neve, and N. Colegrave, “Role of sex and migration in adaptation to sink environments,” Evolution, vol. 68, no. 8. Wiley, pp. 2296–2305, 2014.","apa":"Lagator, M., Morgan, A., Neve, P., & Colegrave, N. (2014). Role of sex and migration in adaptation to sink environments. Evolution. Wiley. https://doi.org/10.1111/evo.12440"},"publication":"Evolution","page":"2296 - 2305","article_type":"original"},{"oa_version":"Published Version","date_updated":"2023-02-23T10:27:31Z","date_created":"2021-07-28T15:32:55Z","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"2083"}]},"author":[{"first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"first_name":"Andrew","last_name":"Morgan","full_name":"Morgan, Andrew"},{"full_name":"Neve, Paul","last_name":"Neve","first_name":"Paul"},{"first_name":"Nick","last_name":"Colegrave","full_name":"Colegrave, Nick"}],"department":[{"_id":"CaGu"}],"publisher":"Dryad","status":"public","title":"Data from: Role of sex and migration in adaptation to sink environments","_id":"9747","year":"2014","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","abstract":[{"lang":"eng","text":"Understanding the effects of sex and migration on adaptation to novel environments remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas reinhardtii, we investigated how sex and migration affected rates of evolutionary rescue in a sink environment, and subsequent changes in fitness following evolutionary rescue. We show that sex and migration affect both the rate of evolutionary rescue and subsequent adaptation. However, their combined effects change as the populations adapt to a sink habitat. Both sex and migration independently increased rates of evolutionary rescue, but the effect of sex on subsequent fitness improvements, following initial rescue, changed with migration, as sex was beneficial in the absence of migration but constraining adaptation when combined with migration. These results suggest that sex and migration are beneficial during the initial stages of adaptation, but can become detrimental as the population adapts to its environment."}],"type":"research_data_reference","date_published":"2014-04-17T00:00:00Z","doi":"10.5061/dryad.s42n1","citation":{"chicago":"Lagator, Mato, Andrew Morgan, Paul Neve, and Nick Colegrave. “Data from: Role of Sex and Migration in Adaptation to Sink Environments.” Dryad, 2014. https://doi.org/10.5061/dryad.s42n1.","short":"M. Lagator, A. Morgan, P. Neve, N. Colegrave, (2014).","mla":"Lagator, Mato, et al. Data from: Role of Sex and Migration in Adaptation to Sink Environments. Dryad, 2014, doi:10.5061/dryad.s42n1.","ieee":"M. Lagator, A. Morgan, P. Neve, and N. Colegrave, “Data from: Role of sex and migration in adaptation to sink environments.” Dryad, 2014.","apa":"Lagator, M., Morgan, A., Neve, P., & Colegrave, N. (2014). Data from: Role of sex and migration in adaptation to sink environments. Dryad. https://doi.org/10.5061/dryad.s42n1","ista":"Lagator M, Morgan A, Neve P, Colegrave N. 2014. Data from: Role of sex and migration in adaptation to sink environments, Dryad, 10.5061/dryad.s42n1.","ama":"Lagator M, Morgan A, Neve P, Colegrave N. Data from: Role of sex and migration in adaptation to sink environments. 2014. doi:10.5061/dryad.s42n1"},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.s42n1"}],"oa":1,"article_processing_charge":"No","day":"17","month":"04"},{"scopus_import":1,"day":"17","citation":{"ama":"Lagator M, Colegrave N, Neve P. Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Proceedings of the Royal Society of London Series B Biological Sciences. 2014;281(1794). doi:10.1098/rspb.2014.1679","ieee":"M. Lagator, N. Colegrave, and P. Neve, “Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses,” Proceedings of the Royal Society of London Series B Biological Sciences, vol. 281, no. 1794. Royal Society, The, 2014.","apa":"Lagator, M., Colegrave, N., & Neve, P. (2014). Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Proceedings of the Royal Society of London Series B Biological Sciences. Royal Society, The. https://doi.org/10.1098/rspb.2014.1679","ista":"Lagator M, Colegrave N, Neve P. 2014. Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Proceedings of the Royal Society of London Series B Biological Sciences. 281(1794), 20141679.","short":"M. Lagator, N. Colegrave, P. Neve, Proceedings of the Royal Society of London Series B Biological Sciences 281 (2014).","mla":"Lagator, Mato, et al. “Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses.” Proceedings of the Royal Society of London Series B Biological Sciences, vol. 281, no. 1794, 20141679, Royal Society, The, 2014, doi:10.1098/rspb.2014.1679.","chicago":"Lagator, Mato, Nick Colegrave, and Paul Neve. “Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses.” Proceedings of the Royal Society of London Series B Biological Sciences. Royal Society, The, 2014. https://doi.org/10.1098/rspb.2014.1679."},"publication":"Proceedings of the Royal Society of London Series B Biological Sciences","date_published":"2014-09-17T00:00:00Z","type":"journal_article","issue":"1794","abstract":[{"lang":"eng","text":" In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments. "}],"intvolume":" 281","title":"Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses","status":"public","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","_id":"2036","oa_version":"Submitted Version","month":"09","quality_controlled":"1","oa":1,"main_file_link":[{"open_access":"1","url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211454/"}],"language":[{"iso":"eng"}],"doi":"10.1098/rspb.2014.1679","article_number":"20141679","publist_id":"5019","department":[{"_id":"CaGu"}],"publisher":"Royal Society, The","publication_status":"published","acknowledgement":"The project was supported by Leverhulme Trust.","year":"2014","volume":281,"date_updated":"2023-02-23T14:06:44Z","date_created":"2018-12-11T11:55:21Z","related_material":{"record":[{"id":"9741","relation":"research_data","status":"public"}]},"author":[{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato"},{"first_name":"Nick","last_name":"Colegrave","full_name":"Colegrave, Nick"},{"full_name":"Neve, Paul","first_name":"Paul","last_name":"Neve"}]},{"article_processing_charge":"No","month":"08","day":"21","date_published":"2014-08-21T00:00:00Z","doi":"10.5061/dryad.85dn7","main_file_link":[{"url":"https://doi.org/10.5061/dryad.85dn7","open_access":"1"}],"citation":{"ama":"Lagator M, Colegrave N, Neve P. Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. 2014. doi:10.5061/dryad.85dn7","ieee":"M. Lagator, N. Colegrave, and P. Neve, “Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses.” Dryad, 2014.","apa":"Lagator, M., Colegrave, N., & Neve, P. (2014). Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses. Dryad. https://doi.org/10.5061/dryad.85dn7","ista":"Lagator M, Colegrave N, Neve P. 2014. Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses, Dryad, 10.5061/dryad.85dn7.","short":"M. Lagator, N. Colegrave, P. Neve, (2014).","mla":"Lagator, Mato, et al. Data from: Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses. Dryad, 2014, doi:10.5061/dryad.85dn7.","chicago":"Lagator, Mato, Nick Colegrave, and Paul Neve. “Data from: Selection History and Epistatic Interactions Impact Dynamics of Adaptation to Novel Environmental Stresses.” Dryad, 2014. https://doi.org/10.5061/dryad.85dn7."},"oa":1,"abstract":[{"text":"In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments.","lang":"eng"}],"type":"research_data_reference","oa_version":"Published Version","date_updated":"2023-02-23T10:25:31Z","date_created":"2021-07-28T08:48:06Z","related_material":{"record":[{"id":"2036","status":"public","relation":"used_in_publication"}]},"author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"full_name":"Colegrave, Nick","first_name":"Nick","last_name":"Colegrave"},{"full_name":"Neve, Paul","last_name":"Neve","first_name":"Paul"}],"department":[{"_id":"CaGu"}],"publisher":"Dryad","title":"Data from: Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses","status":"public","year":"2014","_id":"9741","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf"}]