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Lagator <i>et al.</i>, “Predicting bacterial promoter function and evolution from random sequences,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","ista":"Lagator M, Sarikas S, Steinrück M, Toledo-Aparicio D, Bollback JP, Guet CC, Tkačik G. 2022. Predicting bacterial promoter function and evolution from random sequences. eLife. 11, e64543.","mla":"Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>, vol. 11, e64543, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>.","short":"M. Lagator, S. Sarikas, M. Steinrück, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022).","chicago":"Lagator, Mato, Srdjan Sarikas, Magdalena Steinrück, David Toledo-Aparicio, Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>.","ama":"Lagator M, Sarikas S, Steinrück M, et al. Predicting bacterial promoter function and evolution from random sequences. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>","apa":"Lagator, M., Sarikas, S., Steinrück, M., Toledo-Aparicio, D., Bollback, J. P., Guet, C. C., &#38; Tkačik, G. (2022). Predicting bacterial promoter function and evolution from random sequences. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>"},"external_id":{"pmid":["35080492"],"isi":["000751104400001"]},"quality_controlled":"1","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"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"author":[{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator"},{"last_name":"Sarikas","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","first_name":"Srdjan","full_name":"Sarikas, Srdjan"},{"full_name":"Steinrück, Magdalena","last_name":"Steinrück","orcid":"0000-0003-1229-9719","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","first_name":"Magdalena"},{"first_name":"David","last_name":"Toledo-Aparicio","full_name":"Toledo-Aparicio, David"},{"last_name":"Bollback","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P"},{"last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik","full_name":"Tkačik, Gašper"}],"title":"Predicting bacterial promoter function and evolution from random sequences","corr_author":"1","license":"https://creativecommons.org/licenses/by/4.0/","type":"journal_article","publication_identifier":{"eissn":["2050-084X"]},"date_published":"2022-01-26T00:00:00Z","pmid":1,"_id":"10736","intvolume":"        11","article_number":"e64543","date_created":"2022-02-06T23:01:32Z","scopus_import":"1","language":[{"iso":"eng"}],"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.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"article_type":"original","publisher":"eLife Sciences Publications"},{"publist_id":"8029","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publisher":"Institute of Science and Technology Austria","date_published":"2018-10-30T00:00:00Z","alternative_title":["ISTA Thesis"],"_id":"26","page":"109","OA_place":"publisher","date_created":"2018-12-11T11:44:14Z","language":[{"iso":"eng"}],"related_material":{"record":[{"id":"704","status":"public","relation":"part_of_dissertation"}]},"title":"The influence of sequence context on the evolution of bacterial gene expression","corr_author":"1","type":"dissertation","publication_identifier":{"issn":["2663-337X"]},"abstract":[{"text":"Expression of genes is a fundamental molecular phenotype that is subject to evolution by different types of mutations. Both the rate and the effect of mutations may depend on the DNA sequence context of a particular gene or a particular promoter sequence. In this thesis I investigate the nature of this dependence using simple genetic systems in Escherichia coli. With these systems I explore the evolution of constitutive gene expression from random starting sequences at different loci on the chromosome and at different locations in sequence space. First, I dissect chromosomal neighborhood effects that underlie locus-dependent differences in the potential of a gene under selection to become more highly expressed. Next, I find that the effects of point mutations in promoter sequences are dependent on sequence context, and that an existing energy matrix model performs poorly in predicting relative expression of unrelated sequences. Finally, I show that a substantial fraction of random sequences contain functional promoters and I present an extended thermodynamic model that predicts promoter strength in full sequence space. Taken together, these results provide new insights and guides on how to integrate information on sequence context to improve our qualitative and quantitative understanding of bacterial gene expression, with implications for rapid evolution of drug resistance, de novo evolution of genes, and horizontal gene transfer.","lang":"eng"}],"department":[{"_id":"CaGu"}],"author":[{"full_name":"Steinrück, Magdalena","last_name":"Steinrück","first_name":"Magdalena","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1229-9719"}],"has_accepted_license":"1","citation":{"ieee":"M. Steinrück, “The influence of sequence context on the evolution of bacterial gene expression,” Institute of Science and Technology Austria, 2018.","apa":"Steinrück, M. (2018). <i>The influence of sequence context on the evolution of bacterial gene expression</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:th1059\">https://doi.org/10.15479/AT:ISTA:th1059</a>","ama":"Steinrück M. The influence of sequence context on the evolution of bacterial gene expression. 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th1059\">10.15479/AT:ISTA:th1059</a>","short":"M. Steinrück, The Influence of Sequence Context on the Evolution of Bacterial Gene Expression, Institute of Science and Technology Austria, 2018.","ista":"Steinrück M. 2018. The influence of sequence context on the evolution of bacterial gene expression. Institute of Science and Technology Austria.","mla":"Steinrück, Magdalena. <i>The Influence of Sequence Context on the Evolution of Bacterial Gene Expression</i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:th1059\">10.15479/AT:ISTA:th1059</a>.","chicago":"Steinrück, Magdalena. “The Influence of Sequence Context on the Evolution of Bacterial Gene Expression.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:th1059\">https://doi.org/10.15479/AT:ISTA:th1059</a>."},"year":"2018","supervisor":[{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"month":"10","degree_awarded":"PhD","ddc":["576","579"],"publication_status":"published","status":"public","doi":"10.15479/AT:ISTA:th1059","date_updated":"2026-04-08T14:15:35Z","pubrep_id":"1059","article_processing_charge":"No","day":"30","file":[{"creator":"dernst","date_updated":"2020-07-14T12:45:43Z","file_size":9190845,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2019-02-08T10:51:22Z","embargo_to":"open_access","file_name":"Thesis_Steinrueck_final.docx","file_id":"5941","checksum":"413cbce1cd1debeae3abe2a25dbc70d1","access_level":"closed","relation":"source_file"},{"file_id":"5942","file_name":"Thesis_Steinrueck_final.pdf","date_created":"2019-02-08T10:51:22Z","relation":"main_file","checksum":"3def8b7854c8b42d643597ce0215efac","access_level":"open_access","date_updated":"2021-02-11T11:17:14Z","file_size":7521973,"creator":"dernst","embargo":"2019-11-02","content_type":"application/pdf"}],"file_date_updated":"2021-02-11T11:17:14Z","oa":1,"oa_version":"Published Version"},{"license":"https://creativecommons.org/publicdomain/zero/1.0/","date_updated":"2025-09-10T11:06:52Z","type":"research_data","ddc":["576"],"related_material":{"record":[{"status":"public","relation":"research_paper","id":"704"}]},"doi":"10.15479/AT:ISTA:65","title":"Fastq files for \"Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection\"","status":"public","oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","image":"/images/cc_0.png","name":"Creative Commons Public Domain Dedication (CC0 1.0)","short":"CC0 (1.0)"},"department":[{"_id":"CaGu"}],"oa_version":"Published Version","author":[{"full_name":"Steinrück, Magdalena","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1229-9719","first_name":"Magdalena","last_name":"Steinrück"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C"}],"abstract":[{"lang":"eng","text":"Compressed Fastq files with whole-genome sequencing data of IS-wt strain D and clones from four evolved populations (A11, C08, C10, D08). 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Steinrück, C.C. Guet, (2017).","mla":"Steinrück, Magdalena, and Calin C. Guet. <i>Fastq Files for “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.”</i> Institute of Science and Technology Austria, 2017, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:65\">10.15479/AT:ISTA:65</a>.","ista":"Steinrück M, Guet CC. 2017. Fastq files for ‘Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:65\">10.15479/AT:ISTA:65</a>.","ama":"Steinrück M, Guet CC. Fastq files for “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.” 2017. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:65\">10.15479/AT:ISTA:65</a>","apa":"Steinrück, M., &#38; Guet, C. C. (2017). Fastq files for “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:65\">https://doi.org/10.15479/AT:ISTA:65</a>","ieee":"M. Steinrück and C. C. Guet, “Fastq files for ‘Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.’” Institute of Science and Technology Austria, 2017."},"year":"2017","has_accepted_license":"1","datarep_id":"65","date_created":"2018-12-12T12:31:33Z","month":"04","date_published":"2017-04-11T00:00:00Z","_id":"5564"},{"_id":"704","intvolume":"         6","article_number":"e25100","date_published":"2017-07-25T00:00:00Z","language":[{"iso":"eng"}],"date_created":"2018-12-11T11:48:01Z","scopus_import":"1","publist_id":"6990","isi":1,"publisher":"eLife Sciences Publications","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","quality_controlled":"1","abstract":[{"lang":"eng","text":"How the organization of genes on a chromosome shapes adaptation is essential for understanding evolutionary paths. Here, we investigate how adaptation to rapidly increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance gene inserted at different positions of the Escherichia coli chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene amplifications from other up-mutations, we track in real-time adaptive changes in expression of the drug-resistance gene. We find that the relative contribution of several mutation types differs systematically between loci due to properties of neighboring genes: essentiality, expression, orientation, termination, and presence of duplicates. These properties determine rate and fitness effects of gene amplification, deletions, and mutations compromising transcriptional termination. Thus, the adaptive potential of a gene under selection is a system-property with a complex genetic basis that is specific for each chromosomal locus, and it can be inferred from detailed functional and genomic data."}],"author":[{"full_name":"Steinrück, Magdalena","orcid":"0000-0003-1229-9719","first_name":"Magdalena","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","last_name":"Steinrück"},{"orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","full_name":"Guet, Calin C"}],"department":[{"_id":"CaGu"}],"tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"title":"Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection","related_material":{"record":[{"id":"5564","status":"public","relation":"popular_science"},{"relation":"dissertation_contains","status":"public","id":"26"}]},"type":"journal_article","corr_author":"1","publication_identifier":{"issn":["2050-084X"]},"month":"07","publication":"eLife","has_accepted_license":"1","year":"2017","citation":{"ieee":"M. Steinrück and C. C. Guet, “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","short":"M. Steinrück, C.C. Guet, ELife 6 (2017).","mla":"Steinrück, Magdalena, and Calin C. Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” <i>ELife</i>, vol. 6, e25100, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/eLife.25100\">10.7554/eLife.25100</a>.","ista":"Steinrück M, Guet CC. 2017. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 6, e25100.","chicago":"Steinrück, Magdalena, and Calin C Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/eLife.25100\">https://doi.org/10.7554/eLife.25100</a>.","ama":"Steinrück M, Guet CC. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/eLife.25100\">10.7554/eLife.25100</a>","apa":"Steinrück, M., &#38; Guet, C. C. (2017). 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