[{"date_created":"2022-02-06T23:01:32Z","article_number":"e64543","author":[{"first_name":"Mato","full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator"},{"full_name":"Sarikas, Srdjan","first_name":"Srdjan","last_name":"Sarikas","id":"35F0286E-F248-11E8-B48F-1D18A9856A87"},{"id":"2C023F40-F248-11E8-B48F-1D18A9856A87","last_name":"Steinrück","first_name":"Magdalena","full_name":"Steinrück, Magdalena","orcid":"0000-0003-1229-9719"},{"last_name":"Toledo-Aparicio","first_name":"David","full_name":"Toledo-Aparicio, David"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback","first_name":"Jonathan P","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612"},{"last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C"},{"first_name":"Gašper","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik"}],"type":"journal_article","file_date_updated":"2022-02-07T07:14:09Z","file":[{"date_updated":"2022-02-07T07:14:09Z","relation":"main_file","date_created":"2022-02-07T07:14:09Z","checksum":"decdcdf600ff51e9a9703b49ca114170","file_id":"10739","file_name":"2022_ELife_Lagator.pdf","content_type":"application/pdf","access_level":"open_access","success":1,"file_size":5604343,"creator":"cchlebak"}],"citation":{"short":"M. Lagator, S. Sarikas, M. Steinrück, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022).","apa":"Lagator, M., Sarikas, S., Steinrück, 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","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.” ELife, vol. 11, e64543, eLife Sciences Publications, 2022, doi:10.7554/eLife.64543.","ama":"Lagator M, Sarikas S, Steinrück M, et al. Predicting bacterial promoter function and evolution from random sequences. eLife. 2022;11. doi:10.7554/eLife.64543","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.” ELife. eLife Sciences Publications, 2022. 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."},"project":[{"grant_number":"648440","call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer"}],"publication_status":"published","status":"public","publication":"eLife","scopus_import":"1","has_accepted_license":"1","ddc":["576"],"pmid":1,"date_published":"2022-01-26T00:00:00Z","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"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"}],"intvolume":" 11","article_processing_charge":"No","ec_funded":1,"oa":1,"language":[{"iso":"eng"}],"external_id":{"pmid":["35080492"],"isi":["000751104400001"]},"volume":11,"date_updated":"2025-03-31T16:00:23Z","quality_controlled":"1","publication_identifier":{"eissn":["2050-084X"]},"fulldoi":"https://doi.org/10.7554/eLife.64543","isi":1,"oa_version":"Published Version","year":"2022","day":"26","title":"Predicting bacterial promoter function and evolution from random sequences","corr_author":"1","_id":"10736","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.","publisher":"eLife Sciences Publications","doi":"10.7554/eLife.64543","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"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"01","article_type":"original"},{"publication_status":"published","project":[{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"citation":{"short":"I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik, C.C. Guet, Nature Ecology & Evolution 4 (2020) 612–625.","apa":"Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik, G., & Guet, C. C. (2020). Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. Springer Nature. https://doi.org/10.1038/s41559-020-1132-7","ieee":"I. Tomanek et al., “Gene amplification as a form of population-level gene expression regulation,” Nature Ecology & Evolution, vol. 4, no. 4. Springer Nature, pp. 612–625, 2020.","ama":"Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 2020;4(4):612-625. doi:10.1038/s41559-020-1132-7","mla":"Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution, vol. 4, no. 4, Springer Nature, 2020, pp. 612–25, doi:10.1038/s41559-020-1132-7.","chicago":"Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution. Springer Nature, 2020. https://doi.org/10.1038/s41559-020-1132-7.","ista":"Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC. 2020. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 4(4), 612–625."},"file":[{"date_created":"2020-10-09T09:56:01Z","relation":"main_file","checksum":"ef3bbf42023e30b2c24a6278025d2040","file_id":"8640","date_updated":"2020-10-09T09:56:01Z","content_type":"application/pdf","file_name":"2020_NatureEcolEvo_Tomanek.pdf","creator":"dernst","access_level":"open_access","success":1,"file_size":745242}],"file_date_updated":"2020-10-09T09:56:01Z","type":"journal_article","author":[{"full_name":"Tomanek, Isabella","orcid":"0000-0001-6197-363X","first_name":"Isabella","last_name":"Tomanek","id":"3981F020-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Rok","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","last_name":"Grah"},{"last_name":"Lagator","first_name":"M.","full_name":"Lagator, M."},{"first_name":"A. M. C.","full_name":"Andersson, A. M. C.","last_name":"Andersson"},{"last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","first_name":"Jonathan P"},{"last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","first_name":"Gašper"},{"last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C"}],"issue":"4","page":"612-625","date_created":"2020-04-08T15:20:53Z","language":[{"iso":"eng"}],"external_id":{"pmid":["32152532"],"isi":["000519008300005"]},"oa":1,"article_processing_charge":"No","abstract":[{"text":"Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature.","lang":"eng"}],"intvolume":" 4","date_published":"2020-04-01T00:00:00Z","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"pmid":1,"ddc":["570"],"scopus_import":"1","has_accepted_license":"1","status":"public","publication":"Nature Ecology & Evolution","oa_version":"Submitted Version","isi":1,"fulldoi":"https://doi.org/10.1038/s41559-020-1132-7","quality_controlled":"1","publication_identifier":{"issn":["2397-334X"]},"date_updated":"2026-09-13T22:30:56Z","volume":4,"article_type":"original","month":"04","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1038/s41559-020-1132-7","related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/"}],"record":[{"relation":"research_data","id":"7016","status":"public"},{"status":"public","id":"7383","relation":"research_data"},{"status":"public","id":"8155","relation":"dissertation_contains"},{"status":"public","id":"8653","relation":"used_in_publication"}]},"_id":"7652","acknowledgement":"We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences) Fellowship of the Austrian Academy of Sciences.","publisher":"Springer Nature","title":"Gene amplification as a form of population-level gene expression regulation","day":"01","year":"2020"},{"date_created":"2021-08-09T13:10:02Z","author":[{"id":"35F78294-F248-11E8-B48F-1D18A9856A87","last_name":"Payne","first_name":"Pavel","full_name":"Payne, Pavel","orcid":"0000-0002-2711-9453"},{"full_name":"Geyrhofer, Lukas","first_name":"Lukas","last_name":"Geyrhofer"},{"last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H","first_name":"Nicholas H"},{"last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","first_name":"Jonathan P"}],"type":"research_data_reference","date_updated":"2025-04-15T08:17:50Z","fulldoi":"https://doi.org/10.5061/dryad.42n44","citation":{"ama":"Payne P, Geyrhofer L, Barton NH, Bollback JP. Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations. 2018. doi:10.5061/dryad.42n44","chicago":"Payne, Pavel, Lukas Geyrhofer, Nicholas H Barton, and Jonathan P Bollback. “Data from: CRISPR-Based Herd Immunity Limits Phage Epidemics in Bacterial Populations.” Dryad, 2018. https://doi.org/10.5061/dryad.42n44.","mla":"Payne, Pavel, et al. Data from: CRISPR-Based Herd Immunity Limits Phage Epidemics in Bacterial Populations. Dryad, 2018, doi:10.5061/dryad.42n44.","ieee":"P. Payne, L. Geyrhofer, N. H. Barton, and J. P. Bollback, “Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations.” Dryad, 2018.","ista":"Payne P, Geyrhofer L, Barton NH, Bollback JP. 2018. Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations, Dryad, 10.5061/dryad.42n44.","apa":"Payne, P., Geyrhofer, L., Barton, N. H., & Bollback, J. P. (2018). Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations. Dryad. https://doi.org/10.5061/dryad.42n44","short":"P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, (2018)."},"oa_version":"Published Version","year":"2018","day":"12","title":"Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations","status":"public","_id":"9840","related_material":{"record":[{"relation":"used_in_publication","id":"423","status":"public"}]},"publisher":"Dryad","doi":"10.5061/dryad.42n44","main_file_link":[{"url":"https://doi.org/10.5061/dryad.42n44","open_access":"1"}],"date_published":"2018-03-12T00:00:00Z","month":"03","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","abstract":[{"lang":"eng","text":"Herd immunity, a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes. Even though bacteria have evolved multiple immune systems against their phage pathogens, herd immunity in bacteria remains unexplored. Here we experimentally demonstrate that herd immunity arises during phage epidemics in structured and unstructured Escherichia coli populations consisting of differing frequencies of susceptible and resistant cells harboring CRISPR immunity. In addition, we develop a mathematical model that quantifies how herd immunity is affected by spatial population structure, bacterial growth rate, and phage replication rate. Using our model we infer a general epidemiological rule describing the relative speed of an epidemic in partially resistant spatially structured populations. Our experimental and theoretical findings indicate that herd immunity may be important in bacterial communities, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity."}],"article_processing_charge":"No","oa":1},{"day":"09","year":"2018","title":"CRISPR-based herd immunity can limit phage epidemics in bacterial populations","doi":"10.7554/eLife.32035","_id":"423","related_material":{"record":[{"status":"public","relation":"research_data","id":"9840"}]},"acknowledgement":"We are grateful to Remy Chait for his help and assistance with establishing our experimental setups and to Tobias Bergmiller for valuable insights into some specific experimental details. We thank Luciano Marraffini for donating us the pCas9 plasmid used in this study. We also want to express our gratitude to Seth Barribeau, Andrea Betancourt, Călin Guet, Mato Lagator, Tiago Paixão and Maroš Pleška for valuable discussions on the manuscript. Finally, we would like to thank the \r\neditors and reviewers for their helpful comments and suggestions.","publisher":"eLife Sciences Publications","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"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","month":"03","volume":7,"date_updated":"2025-03-31T16:00:24Z","quality_controlled":"1","fulldoi":"https://doi.org/10.7554/eLife.32035","isi":1,"oa_version":"Published Version","publication":"eLife","publist_id":"7400","status":"public","ddc":["576"],"has_accepted_license":"1","scopus_import":"1","intvolume":" 7","abstract":[{"lang":"eng","text":"Herd immunity, a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes. Even though bacteria have evolved multiple immune systems against their phage pathogens, herd immunity in bacteria remains unexplored. Here we experimentally demonstrate that herd immunity arises during phage epidemics in structured and unstructured Escherichia coli populations consisting of differing frequencies of susceptible and resistant cells harboring CRISPR immunity. In addition, we develop a mathematical model that quantifies how herd immunity is affected by spatial population structure, bacterial growth rate, and phage replication rate. Using our model we infer a general epidemiological rule describing the relative speed of an epidemic in partially resistant spatially structured populations. Our experimental and theoretical findings indicate that herd immunity may be important in bacterial communities, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity."}],"date_published":"2018-03-09T00:00:00Z","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"external_id":{"isi":["000431035800001"]},"language":[{"iso":"eng"}],"oa":1,"article_processing_charge":"No","ec_funded":1,"date_created":"2018-12-11T11:46:23Z","article_number":"e32035","type":"journal_article","author":[{"last_name":"Payne","id":"35F78294-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2711-9453","full_name":"Payne, Pavel","first_name":"Pavel"},{"first_name":"Lukas","full_name":"Geyrhofer, Lukas","last_name":"Geyrhofer"},{"last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","first_name":"Nicholas H"},{"orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"file_date_updated":"2020-07-14T12:46:25Z","citation":{"ista":"Payne P, Geyrhofer L, Barton NH, Bollback JP. 2018. CRISPR-based herd immunity can limit phage epidemics in bacterial populations. eLife. 7, e32035.","ieee":"P. Payne, L. Geyrhofer, N. H. Barton, and J. P. Bollback, “CRISPR-based herd immunity can limit phage epidemics in bacterial populations,” eLife, vol. 7. eLife Sciences Publications, 2018.","ama":"Payne P, Geyrhofer L, Barton NH, Bollback JP. CRISPR-based herd immunity can limit phage epidemics in bacterial populations. eLife. 2018;7. doi:10.7554/eLife.32035","chicago":"Payne, Pavel, Lukas Geyrhofer, Nicholas H Barton, and Jonathan P Bollback. “CRISPR-Based Herd Immunity Can Limit Phage Epidemics in Bacterial Populations.” ELife. eLife Sciences Publications, 2018. https://doi.org/10.7554/eLife.32035.","mla":"Payne, Pavel, et al. “CRISPR-Based Herd Immunity Can Limit Phage Epidemics in Bacterial Populations.” ELife, vol. 7, e32035, eLife Sciences Publications, 2018, doi:10.7554/eLife.32035.","apa":"Payne, P., Geyrhofer, L., Barton, N. H., & Bollback, J. P. (2018). CRISPR-based herd immunity can limit phage epidemics in bacterial populations. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.32035","short":"P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, ELife 7 (2018)."},"file":[{"file_name":"2018_eLife_Payne.pdf","content_type":"application/pdf","access_level":"open_access","file_size":3533881,"creator":"dernst","date_updated":"2020-07-14T12:46:25Z","date_created":"2018-12-17T10:36:07Z","relation":"main_file","file_id":"5689","checksum":"447cf6e680bdc3c01062a8737d876569"}],"project":[{"grant_number":"648440","call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer"}],"publication_status":"published"},{"publist_id":"7987","publication":"Nature Ecology and Evolution","status":"public","has_accepted_license":"1","scopus_import":"1","ddc":["570"],"department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"JoBo"}],"date_published":"2018-09-10T00:00:00Z","intvolume":" 2","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"}],"ec_funded":1,"article_processing_charge":"No","oa":1,"language":[{"iso":"eng"}],"external_id":{"isi":["000447947600021"]},"date_created":"2018-12-11T11:44:27Z","page":"1633 - 1643","author":[{"last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7777-546X","full_name":"Igler, Claudia","first_name":"Claudia"},{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato","full_name":"Lagator, Mato"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455","full_name":"Tkacik, Gasper"},{"last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P"},{"first_name":"Calin C","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet"}],"issue":"10","type":"journal_article","file_date_updated":"2020-07-14T12:47:37Z","file":[{"creator":"dernst","access_level":"open_access","file_size":1135973,"content_type":"application/pdf","file_name":"2018_NatureEcology_Igler.pdf","relation":"main_file","date_created":"2020-05-14T11:28:52Z","checksum":"383a2e2c944a856e2e821ec8e7bf71b6","file_id":"7830","date_updated":"2020-07-14T12:47:37Z"}],"citation":{"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","short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology and Evolution 2 (2018) 1633–1643.","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","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.","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.","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.","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. 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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.","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","ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","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","short":"M. Lagator, S. Sarikas, H. Acar, J.P. Bollback, C.C. Guet, ELife 6 (2017)."},"scopus_import":"1","has_accepted_license":"1","ddc":["576"],"publist_id":"7244","status":"public","publication":"eLife","ec_funded":1,"article_processing_charge":"No","oa":1,"external_id":{"isi":["000425868200001"]},"language":[{"iso":"eng"}],"date_published":"2017-11-13T00:00:00Z","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. "}],"intvolume":" 6","fulldoi":"https://doi.org/10.7554/eLife.28921","publication_identifier":{"issn":["2050-084X"]},"quality_controlled":"1","date_updated":"2025-09-11T07:40:30Z","volume":6,"oa_version":"Published Version","isi":1,"_id":"570","publisher":"eLife Sciences Publications","doi":"10.7554/eLife.28921","title":"Regulatory network structure determines patterns of intermolecular epistasis","corr_author":"1","year":"2017","day":"13","month":"11","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","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"}},{"file":[{"checksum":"59cdd4400fb41280122d414fea971546","file_id":"5306","relation":"main_file","date_created":"2018-12-12T10:17:49Z","date_updated":"2020-07-14T12:48:16Z","creator":"system","file_size":2441529,"access_level":"open_access","content_type":"application/pdf","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf"},{"date_updated":"2020-07-14T12:48:16Z","checksum":"b69024880558b858eb8c5d47a92b6377","file_id":"5307","date_created":"2018-12-12T10:17:50Z","relation":"main_file","file_size":3752660,"access_level":"open_access","creator":"system","file_name":"IST-2017-841-v1+2_elife-25192-figures-v2.pdf","content_type":"application/pdf"}],"pubrep_id":"841","citation":{"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","short":"M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017).","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.","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.","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","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."},"publication_status":"published","project":[{"grant_number":"618091","call_identifier":"FP7","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"},{"name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734"},{"grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer"}],"author":[{"last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato","first_name":"Mato"},{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","first_name":"Tiago","full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","first_name":"Nicholas H","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback","first_name":"Jonathan P","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"type":"journal_article","date_created":"2018-12-11T11:49:23Z","article_number":"e25192","file_date_updated":"2020-07-14T12:48:16Z","ec_funded":1,"article_processing_charge":"Yes","oa":1,"language":[{"iso":"eng"}],"external_id":{"isi":["000404024800001"]},"date_published":"2017-05-18T00:00:00Z","department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"abstract":[{"lang":"eng","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."}],"intvolume":" 6","publist_id":"6460","publication":"eLife","status":"public","scopus_import":"1","has_accepted_license":"1","ddc":["576"],"isi":1,"oa_version":"Published Version","date_updated":"2025-07-10T12:01:50Z","volume":6,"fulldoi":"https://doi.org/10.7554/eLife.25192","quality_controlled":"1","publication_identifier":{"issn":["2050-084X"]},"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"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"05","title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","year":"2017","day":"18","_id":"954","publisher":"eLife Sciences Publications","doi":"10.7554/eLife.25192"},{"title":"Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family","day":"04","year":"2017","doi":"10.1098/rsif.2016.0139","_id":"1077","related_material":{"record":[{"status":"public","id":"9864","relation":"research_data"}]},"publisher":"Royal Society","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"},"month":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2026-08-27T12:09:33Z","volume":14,"fulldoi":"https://doi.org/10.1098/rsif.2016.0139","quality_controlled":"1","publication_identifier":{"issn":["1742-5689"]},"isi":1,"oa_version":"Published Version","publist_id":"6303","status":"public","publication":"Journal of the Royal Society Interface","ddc":["570"],"scopus_import":"1","has_accepted_license":"1","oa":1,"external_id":{"isi":["000393380400001"]},"language":[{"iso":"eng"}],"article_processing_charge":"Yes (in subscription journal)","ec_funded":1,"abstract":[{"text":"Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the fX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.","lang":"eng"}],"intvolume":" 14","date_published":"2017-01-04T00:00:00Z","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"type":"journal_article","issue":"126","author":[{"first_name":"Rodrigo A","orcid":"0000-0002-5837-2793","full_name":"Fernandes Redondo, Rodrigo A","id":"409D5C96-F248-11E8-B48F-1D18A9856A87","last_name":"Fernandes Redondo"},{"id":"2A181218-F248-11E8-B48F-1D18A9856A87","last_name":"Vladar","first_name":"Harold","full_name":"Vladar, Harold","orcid":"0000-0002-5985-7653"},{"full_name":"Włodarski, Tomasz","first_name":"Tomasz","last_name":"Włodarski"},{"orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"article_number":"20160139","date_created":"2018-12-11T11:50:01Z","file_date_updated":"2019-01-18T09:14:02Z","citation":{"ista":"Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. 2017. Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. Journal of the Royal Society Interface. 14(126), 20160139.","mla":"Fernandes Redondo, Rodrigo A., et al. “Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family.” Journal of the Royal Society Interface, vol. 14, no. 126, 20160139, Royal Society, 2017, doi:10.1098/rsif.2016.0139.","ama":"Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. Journal of the Royal Society Interface. 2017;14(126). doi:10.1098/rsif.2016.0139","chicago":"Fernandes Redondo, Rodrigo A, Harold de Vladar, Tomasz Włodarski, and Jonathan P Bollback. “Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family.” Journal of the Royal Society Interface. Royal Society, 2017. https://doi.org/10.1098/rsif.2016.0139.","ieee":"R. A. Fernandes Redondo, H. de Vladar, T. Włodarski, and J. P. Bollback, “Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family,” Journal of the Royal Society Interface, vol. 14, no. 126. Royal Society, 2017.","apa":"Fernandes Redondo, R. A., de Vladar, H., Włodarski, T., & Bollback, J. P. (2017). Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. Journal of the Royal Society Interface. Royal Society. https://doi.org/10.1098/rsif.2016.0139","short":"R.A. Fernandes Redondo, H. de Vladar, T. Włodarski, J.P. Bollback, Journal of the Royal Society Interface 14 (2017)."},"file":[{"file_size":1092015,"access_level":"open_access","success":1,"creator":"dernst","content_type":"application/pdf","file_name":"2017_JRSI_Redondo.pdf","date_updated":"2019-01-18T09:14:02Z","file_id":"5843","date_created":"2019-01-18T09:14:02Z","relation":"main_file"}],"publication_status":"published","project":[{"name":"Limits to selection in biology and in evolutionary computation","grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"name":"Selective Barriers to Horizontal Gene Transfer","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"648440"}]},{"citation":{"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","short":"M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769.","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.","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.","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."},"pubrep_id":"588","file":[{"checksum":"1f456ce1d2aa2f67176a1709f9702ecf","file_id":"4751","relation":"main_file","date_created":"2018-12-12T10:09:27Z","date_updated":"2020-07-14T12:44:53Z","file_name":"IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf","content_type":"application/pdf","creator":"system","file_size":648115,"access_level":"open_access"}],"project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"}],"publication_status":"published","page":"761 - 769","date_created":"2018-12-11T11:51:57Z","type":"journal_article","author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","last_name":"Lagator","first_name":"Mato","full_name":"Lagator, Mato"},{"id":"46613666-F248-11E8-B48F-1D18A9856A87","last_name":"Igler","first_name":"Claudia","full_name":"Igler, Claudia"},{"last_name":"Moreno","full_name":"Moreno, Anaisa","first_name":"Anaisa"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"issue":"3","file_date_updated":"2020-07-14T12:44:53Z","abstract":[{"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.","lang":"eng"}],"intvolume":" 33","department":[{"_id":"CaGu"},{"_id":"JoBo"}],"date_published":"2016-03-01T00:00:00Z","language":[{"iso":"eng"}],"external_id":{"isi":["000371219500014"]},"oa":1,"article_processing_charge":"No","ec_funded":1,"status":"public","publication":"Molecular Biology and Evolution","publist_id":"5772","ddc":["570","576"],"scopus_import":"1","has_accepted_license":"1","isi":1,"oa_version":"Published Version","volume":33,"date_updated":"2025-09-18T14:11:47Z","quality_controlled":"1","fulldoi":"https://doi.org/10.1093/molbev/msv269","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"},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"03","day":"01","year":"2016","corr_author":"1","title":"Epistatic interactions in the arabinose cis-regulatory element","doi":"10.1093/molbev/msv269","publisher":"Oxford University Press","_id":"1427"},{"oa_version":"Published Version","citation":{"short":"R.A. Fernandes Redondo, H. de Vladar, T. Włodarski, J.P. Bollback, (2016).","apa":"Fernandes Redondo, R. A., de Vladar, H., Włodarski, T., & Bollback, J. P. (2016). Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. The Royal Society. https://doi.org/10.6084/m9.figshare.4315652.v1","mla":"Fernandes Redondo, Rodrigo A., et al. Data from Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family. The Royal Society, 2016, doi:10.6084/m9.figshare.4315652.v1.","ama":"Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family. 2016. doi:10.6084/m9.figshare.4315652.v1","chicago":"Fernandes Redondo, Rodrigo A, Harold de Vladar, Tomasz Włodarski, and Jonathan P Bollback. “Data from Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the ΦX174 Phage Family.” The Royal Society, 2016. https://doi.org/10.6084/m9.figshare.4315652.v1.","ieee":"R. A. Fernandes Redondo, H. de Vladar, T. Włodarski, and J. P. Bollback, “Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family.” The Royal Society, 2016.","ista":"Fernandes Redondo RA, de Vladar H, Włodarski T, Bollback JP. 2016. Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family, The Royal Society, 10.6084/m9.figshare.4315652.v1."},"fulldoi":"https://doi.org/10.6084/m9.figshare.4315652.v1","date_created":"2021-08-10T08:29:47Z","author":[{"last_name":"Fernandes Redondo","id":"409D5C96-F248-11E8-B48F-1D18A9856A87","full_name":"Fernandes Redondo, Rodrigo A","orcid":"0000-0002-5837-2793","first_name":"Rodrigo A"},{"last_name":"de Vladar","id":"2A181218-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5985-7653","full_name":"de Vladar, Harold","first_name":"Harold"},{"last_name":"Włodarski","first_name":"Tomasz","full_name":"Włodarski, Tomasz"},{"last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P"}],"date_updated":"2026-08-27T12:09:34Z","type":"research_data_reference","date_published":"2016-12-14T00:00:00Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"12","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"abstract":[{"lang":"eng","text":"Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by, first, reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima."}],"article_processing_charge":"No","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.6084/m9.figshare.4315652.v1"}],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"1077"}]},"_id":"9864","publisher":"The Royal Society","doi":"10.6084/m9.figshare.4315652.v1","year":"2016","day":"14","title":"Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family","status":"public"},{"publication":"BMC Genomics","publist_id":"5009","status":"public","has_accepted_license":"1","scopus_import":"1","ddc":["570"],"article_processing_charge":"No","external_id":{"isi":["000341528300001"]},"oa":1,"language":[{"iso":"eng"}],"date_published":"2014-08-08T00:00:00Z","department":[{"_id":"JoBo"}],"abstract":[{"text":"Background: CRISPR is a microbial immune system likely to be involved in host-parasite coevolution. It functions using target sequences encoded by the bacterial genome, which interfere with invading nucleic acids using a homology-dependent system. The system also requires protospacer associated motifs (PAMs), short motifs close to the target sequence that are required for interference in CRISPR types I and II. Here, we investigate whether PAMs are depleted in phage genomes due to selection pressure to escape recognition.Results: To this end, we analyzed two data sets. Phages infecting all bacterial hosts were analyzed first, followed by a detailed analysis of phages infecting the genus Streptococcus, where PAMs are best understood. We use two different measures of motif underrepresentation that control for codon bias and the frequency of submotifs. We compare phages infecting species with a particular CRISPR type to those infecting species without that type. Since only known PAMs were investigated, the analysis is restricted to CRISPR types I-C and I-E and in Streptococcus to types I-C and II. We found evidence for PAM depletion in Streptococcus phages infecting hosts with CRISPR type I-C, in Vibrio phages infecting hosts with CRISPR type I-E and in Streptococcus thermopilus phages infecting hosts with type II-A, known as CRISPR3.Conclusions: The observed motif depletion in phages with hosts having CRISPR can be attributed to selection rather than to mutational bias, as mutational bias should affect the phages of all hosts. This observation implies that the CRISPR system has been efficient in the groups discussed here.","lang":"eng"}],"intvolume":" 15","issue":"1","author":[{"id":"2BB22BC2-F248-11E8-B48F-1D18A9856A87","last_name":"Kupczok","first_name":"Anne","full_name":"Kupczok, Anne"},{"full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"type":"journal_article","date_created":"2018-12-11T11:55:23Z","article_number":"663","file_date_updated":"2020-07-14T12:45:26Z","pubrep_id":"396","file":[{"content_type":"application/pdf","file_name":"IST-2015-396-v1+1_1471-2164-15-663.pdf","creator":"system","access_level":"open_access","file_size":1489769,"date_created":"2018-12-12T10:11:24Z","relation":"main_file","checksum":"3f6d2776b90a842a28359cc957d3d04b","file_id":"4878","date_updated":"2020-07-14T12:45:26Z"}],"citation":{"ista":"Kupczok A, Bollback JP. 2014. Motif depletion in bacteriophages infecting hosts with CRISPR systems. BMC Genomics. 15(1), 663.","mla":"Kupczok, Anne, and Jonathan P. Bollback. “Motif Depletion in Bacteriophages Infecting Hosts with CRISPR Systems.” BMC Genomics, vol. 15, no. 1, 663, BioMed Central, 2014, doi:10.1186/1471-2164-15-663.","ieee":"A. Kupczok and J. P. Bollback, “Motif depletion in bacteriophages infecting hosts with CRISPR systems,” BMC Genomics, vol. 15, no. 1. BioMed Central, 2014.","ama":"Kupczok A, Bollback JP. Motif depletion in bacteriophages infecting hosts with CRISPR systems. BMC Genomics. 2014;15(1). doi:10.1186/1471-2164-15-663","chicago":"Kupczok, Anne, and Jonathan P Bollback. “Motif Depletion in Bacteriophages Infecting Hosts with CRISPR Systems.” BMC Genomics. BioMed Central, 2014. https://doi.org/10.1186/1471-2164-15-663.","short":"A. Kupczok, J.P. Bollback, BMC Genomics 15 (2014).","apa":"Kupczok, A., & Bollback, J. P. (2014). Motif depletion in bacteriophages infecting hosts with CRISPR systems. BMC Genomics. BioMed Central. https://doi.org/10.1186/1471-2164-15-663"},"publication_status":"published","title":"Motif depletion in bacteriophages infecting hosts with CRISPR systems","corr_author":"1","year":"2014","day":"08","publisher":"BioMed Central","_id":"2042","doi":"10.1186/1471-2164-15-663","tmp":{"name":"Creative Commons Public Domain Dedication (CC0 1.0)","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","short":"CC0 (1.0)","image":"/images/cc_0.png"},"month":"08","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","date_updated":"2025-09-29T11:52:17Z","volume":15,"fulldoi":"https://doi.org/10.1186/1471-2164-15-663","quality_controlled":"1","isi":1,"oa_version":"Published Version"},{"file_date_updated":"2020-07-14T12:45:40Z","date_created":"2018-12-11T11:57:30Z","author":[{"first_name":"Rodrigo A","orcid":"0000-0002-5837-2793","full_name":"Fernandes Redondo, Rodrigo A","id":"409D5C96-F248-11E8-B48F-1D18A9856A87","last_name":"Fernandes Redondo"},{"first_name":"Anne","full_name":"Kupczok, Anne","id":"2BB22BC2-F248-11E8-B48F-1D18A9856A87","last_name":"Kupczok"},{"id":"2DB195CA-F248-11E8-B48F-1D18A9856A87","last_name":"Stift","first_name":"Gertraud","full_name":"Stift, Gertraud"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback","first_name":"Jonathan P","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612"}],"issue":"3","type":"journal_article","publication_status":"published","pubrep_id":"398","file":[{"relation":"main_file","date_created":"2018-12-12T10:17:36Z","checksum":"0751ec74b695567e0cdf02aaf9c26829","file_id":"5291","date_updated":"2020-07-14T12:45:40Z","creator":"system","access_level":"open_access","file_size":130026,"content_type":"application/pdf","file_name":"IST-2015-398-v1+1_Genome_Announc.-2013-Redondo-.pdf"}],"citation":{"apa":"Fernandes Redondo, R. A., Kupczok, A., Stift, G., & Bollback, J. P. (2013). Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis. Genome Announcements. American Society for Microbiology. https://doi.org/10.1128/genomeA.00216-13","short":"R.A. Fernandes Redondo, A. Kupczok, G. Stift, J.P. Bollback, Genome Announcements 1 (2013).","ista":"Fernandes Redondo RA, Kupczok A, Stift G, Bollback JP. 2013. Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis. Genome Announcements. 1(3).","chicago":"Fernandes Redondo, Rodrigo A, Anne Kupczok, Gertraud Stift, and Jonathan P Bollback. “Complete Genome Sequence of the Novel Phage MG-B1 Infecting Bacillus Weihenstephanensis.” Genome Announcements. American Society for Microbiology, 2013. https://doi.org/10.1128/genomeA.00216-13.","ieee":"R. A. Fernandes Redondo, A. Kupczok, G. Stift, and J. P. Bollback, “Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis,” Genome Announcements, vol. 1, no. 3. American Society for Microbiology, 2013.","mla":"Fernandes Redondo, Rodrigo A., et al. “Complete Genome Sequence of the Novel Phage MG-B1 Infecting Bacillus Weihenstephanensis.” Genome Announcements, vol. 1, no. 3, American Society for Microbiology, 2013, doi:10.1128/genomeA.00216-13.","ama":"Fernandes Redondo RA, Kupczok A, Stift G, Bollback JP. Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis. Genome Announcements. 2013;1(3). doi:10.1128/genomeA.00216-13"},"has_accepted_license":"1","scopus_import":1,"ddc":["576"],"publication":"Genome Announcements","status":"public","publist_id":"4516","department":[{"_id":"JoBo"},{"_id":"LifeSc"}],"date_published":"2013-06-13T00:00:00Z","abstract":[{"text":"Here, we describe a novel virulent bacteriophage that infects Bacillus weihenstephanensis, isolated from soil in Austria. It is the first phage to be discovered that infects this species. Here, we present the complete genome sequence of this podovirus. ","lang":"eng"}],"intvolume":" 1","oa":1,"language":[{"iso":"eng"}],"quality_controlled":"1","fulldoi":"https://doi.org/10.1128/genomeA.00216-13","volume":1,"date_updated":"2024-10-09T20:55:15Z","oa_version":"Published Version","publisher":"American Society for Microbiology","_id":"2410","doi":"10.1128/genomeA.00216-13","year":"2013","day":"13","title":"Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis","corr_author":"1","month":"06","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"language":[{"iso":"eng"}],"oa":1,"external_id":{"isi":["000321524500001"]},"article_processing_charge":"No","abstract":[{"lang":"eng","text":"Background: The CRISPR/Cas system is known to act as an adaptive and heritable immune system in Eubacteria and Archaea. Immunity is encoded in an array of spacer sequences. Each spacer can provide specific immunity to invasive elements that carry the same or a similar sequence. Even in closely related strains, spacer content is very dynamic and evolves quickly. Standard models of nucleotide evolutioncannot be applied to quantify its rate of change since processes other than single nucleotide changes determine its evolution.Methods We present probabilistic models that are specific for spacer content evolution. They account for the different processes of insertion and deletion. Insertions can be constrained to occur on one end only or are allowed to occur throughout the array. One deletion event can affect one spacer or a whole fragment of adjacent spacers. Parameters of the underlying models are estimated for a pair of arrays by maximum likelihood using explicit ancestor enumeration.Results Simulations show that parameters are well estimated on average under the models presented here. There is a bias in the rate estimation when including fragment deletions. The models also estimate times between pairs of strains. But with increasing time, spacer overlap goes to zero, and thus there is an upper bound on the distance that can be estimated. Spacer content similarities are displayed in a distance based phylogeny using the estimated times.We use the presented models to analyze different Yersinia pestis data sets and find that the results among them are largely congruent. The models also capture the variation in diversity of spacers among the data sets. A comparison of spacer-based phylogenies and Cas gene phylogenies shows that they resolve very different time scales for this data set.Conclusions The simulations and data analyses show that the presented models are useful for quantifying spacer content evolution and for displaying spacer content similarities of closely related strains in a phylogeny. This allows for comparisons of different CRISPR arrays or for comparisons between CRISPR arrays and nucleotide substitution rates."}],"intvolume":" 13","department":[{"_id":"JoBo"}],"date_published":"2013-02-26T00:00:00Z","publist_id":"4514","publication":"BMC Evolutionary Biology","status":"public","ddc":["576"],"scopus_import":"1","has_accepted_license":"1","citation":{"short":"A. Kupczok, J.P. Bollback, BMC Evolutionary Biology 13 (2013) 54–54.","apa":"Kupczok, A., & Bollback, J. P. (2013). Probabilistic models for CRISPR spacer content evolution . BMC Evolutionary Biology. BioMed Central. https://doi.org/10.1186/1471-2148-13-54","chicago":"Kupczok, Anne, and Jonathan P Bollback. “Probabilistic Models for CRISPR Spacer Content Evolution .” BMC Evolutionary Biology. BioMed Central, 2013. https://doi.org/10.1186/1471-2148-13-54.","ieee":"A. Kupczok and J. P. Bollback, “Probabilistic models for CRISPR spacer content evolution ,” BMC Evolutionary Biology, vol. 13, no. 1. BioMed Central, pp. 54–54, 2013.","ama":"Kupczok A, Bollback JP. Probabilistic models for CRISPR spacer content evolution . BMC Evolutionary Biology. 2013;13(1):54-54. doi:10.1186/1471-2148-13-54","mla":"Kupczok, Anne, and Jonathan P. Bollback. “Probabilistic Models for CRISPR Spacer Content Evolution .” BMC Evolutionary Biology, vol. 13, no. 1, BioMed Central, 2013, pp. 54–54, doi:10.1186/1471-2148-13-54.","ista":"Kupczok A, Bollback JP. 2013. Probabilistic models for CRISPR spacer content evolution . BMC Evolutionary Biology. 13(1), 54–54."},"pubrep_id":"397","file":[{"file_size":518729,"access_level":"open_access","creator":"system","content_type":"application/pdf","file_name":"IST-2015-397-v1+1_1471-2148-13-54.pdf","date_updated":"2020-07-14T12:45:40Z","checksum":"029c7e0b198c19312b66ecce3cabb22f","file_id":"5268","relation":"main_file","date_created":"2018-12-12T10:17:15Z"}],"publication_status":"published","type":"journal_article","issue":"1","author":[{"full_name":"Kupczok, Anne","first_name":"Anne","last_name":"Kupczok","id":"2BB22BC2-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"page":"54 - 54","date_created":"2018-12-11T11:57:31Z","file_date_updated":"2020-07-14T12:45:40Z","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"},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"02","corr_author":"1","title":"Probabilistic models for CRISPR spacer content evolution ","day":"26","year":"2013","doi":"10.1186/1471-2148-13-54","_id":"2412","publisher":"BioMed Central","isi":1,"oa_version":"Published Version","date_updated":"2025-09-29T14:15:59Z","volume":13,"fulldoi":"https://doi.org/10.1186/1471-2148-13-54","quality_controlled":"1"},{"file_date_updated":"2020-07-14T12:46:36Z","issue":"1","author":[{"last_name":"Ward","full_name":"Ward, Melissa","first_name":"Melissa"},{"last_name":"Lycett","full_name":"Lycett, Samantha","first_name":"Samantha"},{"first_name":"Dorita","full_name":"Avila, Dorita","last_name":"Avila"},{"orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Leigh Brown, Andrew","first_name":"Andrew","last_name":"Leigh Brown"}],"type":"journal_article","date_created":"2018-12-11T11:46:49Z","article_number":"222","publication_status":"published","pubrep_id":"941","file":[{"file_name":"IST-2018-941-v1+1_2013_Bollback_Evolutionary_interactionspdf.pdf","content_type":"application/pdf","creator":"system","access_level":"open_access","file_size":1150052,"date_created":"2018-12-12T10:08:59Z","relation":"main_file","file_id":"4722","checksum":"52cf48a7c1794676ae8b0029573a84a9","date_updated":"2020-07-14T12:46:36Z"}],"citation":{"ista":"Ward M, Lycett S, Avila D, Bollback JP, Leigh Brown A. 2013. Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza. BMC Evolutionary Biology. 13(1), 222.","ieee":"M. Ward, S. Lycett, D. Avila, J. P. Bollback, and A. Leigh Brown, “Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza,” BMC Evolutionary Biology, vol. 13, no. 1. BioMed Central, 2013.","mla":"Ward, Melissa, et al. “Evolutionary Interactions between Haemagglutinin and Neuraminidase in Avian Influenza.” BMC Evolutionary Biology, vol. 13, no. 1, 222, BioMed Central, 2013, doi:10.1186/1471-2148-13-222.","ama":"Ward M, Lycett S, Avila D, Bollback JP, Leigh Brown A. Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza. BMC Evolutionary Biology. 2013;13(1). doi:10.1186/1471-2148-13-222","chicago":"Ward, Melissa, Samantha Lycett, Dorita Avila, Jonathan P Bollback, and Andrew Leigh Brown. “Evolutionary Interactions between Haemagglutinin and Neuraminidase in Avian Influenza.” BMC Evolutionary Biology. BioMed Central, 2013. https://doi.org/10.1186/1471-2148-13-222.","short":"M. Ward, S. Lycett, D. Avila, J.P. Bollback, A. Leigh Brown, BMC Evolutionary Biology 13 (2013).","apa":"Ward, M., Lycett, S., Avila, D., Bollback, J. P., & Leigh Brown, A. (2013). Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza. BMC Evolutionary Biology. BioMed Central. https://doi.org/10.1186/1471-2148-13-222"},"scopus_import":"1","has_accepted_license":"1","ddc":["576"],"publication":"BMC Evolutionary Biology","status":"public","publist_id":"7320","article_processing_charge":"No","oa":1,"language":[{"iso":"eng"}],"external_id":{"isi":["000326620200001"]},"department":[{"_id":"JoBo"}],"date_published":"2013-10-09T00:00:00Z","intvolume":" 13","abstract":[{"text":"Background: Reassortment between the RNA segments encoding haemagglutinin (HA) and neuraminidase (NA), the major antigenic influenza proteins, produces viruses with novel HA and NA subtype combinations and has preceded the emergence of pandemic strains. It has been suggested that productive viral infection requires a balance in the level of functional activity of HA and NA, arising from their closely interacting roles in the viral life cycle, and that this functional balance could be mediated by genetic changes in the HA and NA. Here, we investigate how the selective pressure varies for H7 avian influenza HA on different NA subtype backgrounds. Results: By extending Bayesian stochastic mutational mapping methods to calculate the ratio of the rate of non-synonymous change to the rate of synonymous change (d N/d S), we found the average d N/d S across the avian influenza H7 HA1 region to be significantly greater on an N2 NA subtype background than on an N1, N3 or N7 background. Observed differences in evolutionary rates of H7 HA on different NA subtype backgrounds could not be attributed to underlying differences between avian host species or virus pathogenicity. Examination of d N/d S values for each subtype on a site-by-site basis indicated that the elevated d N/d S on the N2 NA background was a result of increased selection, rather than a relaxation of selective constraint. Conclusions: Our results are consistent with the hypothesis that reassortment exposes influenza HA to significant changes in selective pressure through genetic interactions with NA. Such epistatic effects might be explicitly accounted for in future models of influenza evolution.","lang":"eng"}],"fulldoi":"https://doi.org/10.1186/1471-2148-13-222","quality_controlled":"1","date_updated":"2025-09-30T07:28:51Z","volume":13,"oa_version":"Published Version","isi":1,"_id":"500","publisher":"BioMed Central","acknowledgement":"This work was supported by the Biotechnology and Biological Sciences Research Council, the Government of the Republic of Panama, the Interdisciplinary Centre for Human and Avian Influenza Research (www.ichair-flu.org) funded by the Scottish Funding Council, and the Institute for Science and Technology Austria.\r\nCC BY 2.0\r\n","doi":"10.1186/1471-2148-13-222","title":"Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza","year":"2013","day":"09","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","month":"10","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"}},{"day":"09","year":"2010","status":"public","publication":"Genome Biology and Evolution","publist_id":"1100","title":"Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation","doi":"10.1093/gbe/evq031","_id":"4358","publisher":"Oxford University Press","extern":1,"intvolume":" 2","abstract":[{"lang":"eng","text":"Phenotypic biotyping has traditionally been used to differentiate bacteria occupying distinct ecological niches such as host species. For example, the capacity of Staphylococcus aureus from sheep to coagulate ruminant plasma, reported over 60 years ago, led to the description of small ruminant and bovine S. aureus ecovars. The great majority of small ruminant isolates are represented by a single, widespread clonal complex (CC133) of S. aureus, but its evolutionary origin and the molecular basis for its host tropism remain unknown. Here, we provide evidence that the CC133 clone evolved as the result of a human to ruminant host jump followed by adaptive genome diversification. Comparative whole-genome sequencing revealed molecular evidence for host adaptation including gene decay and diversification of proteins involved in host-pathogen interactions. Importantly, several novel mobile genetic elements encoding virulence proteins with attenuated or enhanced activity in ruminants were widely distributed in CC133 isolates, suggesting a key role in its host-specific interactions. To investigate this further, we examined the activity of a novel staphylococcal pathogenicity island (SaPIov2) found in the great majority of CC133 isolates which encodes a variant of the chromosomally encoded von Willebrand-binding protein (vWbp(Sov2)), previously demonstrated to have coagulase activity for human plasma. Remarkably, we discovered that SaPIov2 confers the ability to coagulate ruminant plasma suggesting an important role in ruminant disease pathogenesis and revealing the origin of a defining phenotype of the classical S. aureus biotyping scheme. Taken together, these data provide broad new insights into the origin and molecular basis of S. aureus ruminant host specificity."}],"date_published":"2010-06-09T00:00:00Z","month":"06","page":"454 - 466","volume":2,"date_created":"2018-12-11T12:08:27Z","type":"journal_article","date_updated":"2021-01-12T07:56:23Z","author":[{"first_name":"Caitriona","full_name":"Guinane, Caitriona M","last_name":"Guinane"},{"last_name":"Ben Zakour","first_name":"Nouri","full_name":"Ben Zakour, Nouri L"},{"last_name":"Tormo Mas","first_name":"Maria","full_name":"Tormo-Mas, Maria A"},{"full_name":"Weinert, Lucy A","first_name":"Lucy","last_name":"Weinert"},{"full_name":"Lowder, Bethan V","first_name":"Bethan","last_name":"Lowder"},{"last_name":"Cartwright","first_name":"Robyn","full_name":"Cartwright, Robyn A"},{"last_name":"Smyth","full_name":"Smyth, Davida S","first_name":"Davida"},{"last_name":"Smyth","full_name":"Smyth, Cyril J","first_name":"Cyril"},{"full_name":"Lindsay, Jodi A","first_name":"Jodi","last_name":"Lindsay"},{"last_name":"Gould","full_name":"Gould, Katherine A","first_name":"Katherine"},{"full_name":"Witney, Adam","first_name":"Adam","last_name":"Witney"},{"last_name":"Hinds","full_name":"Hinds, Jason","first_name":"Jason"},{"orcid":"0000-0002-4624-4612","full_name":"Jonathan Bollback","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Rambaut, Andrew","first_name":"Andrew","last_name":"Rambaut"},{"last_name":"Penades","full_name":"Penades, Jose R","first_name":"Jose"},{"first_name":"J Ross","full_name":"Fitzgerald, J Ross","last_name":"Fitzgerald"}],"quality_controlled":0,"fulldoi":"https://doi.org/10.1093/gbe/evq031","citation":{"ista":"Guinane C, Ben Zakour N, Tormo Mas M, Weinert L, Lowder B, Cartwright R, Smyth D, Smyth C, Lindsay J, Gould K, Witney A, Hinds J, Bollback JP, Rambaut A, Penades J, Fitzgerald JR. 2010. Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation. Genome Biology and Evolution. 2, 454–466.","ama":"Guinane C, Ben Zakour N, Tormo Mas M, et al. Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation. Genome Biology and Evolution. 2010;2:454-466. doi:10.1093/gbe/evq031","chicago":"Guinane, Caitriona, Nouri Ben Zakour, Maria Tormo Mas, Lucy Weinert, Bethan Lowder, Robyn Cartwright, Davida Smyth, et al. “Evolutionary Genomics of Staphylococcus Aureus Reveals Insights into the Origin and Molecular Basis of Ruminant Host Adaptation.” Genome Biology and Evolution. Oxford University Press, 2010. https://doi.org/10.1093/gbe/evq031.","mla":"Guinane, Caitriona, et al. “Evolutionary Genomics of Staphylococcus Aureus Reveals Insights into the Origin and Molecular Basis of Ruminant Host Adaptation.” Genome Biology and Evolution, vol. 2, Oxford University Press, 2010, pp. 454–66, doi:10.1093/gbe/evq031.","ieee":"C. Guinane et al., “Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation,” Genome Biology and Evolution, vol. 2. Oxford University Press, pp. 454–466, 2010.","short":"C. Guinane, N. Ben Zakour, M. Tormo Mas, L. Weinert, B. Lowder, R. Cartwright, D. Smyth, C. Smyth, J. Lindsay, K. Gould, A. Witney, J. Hinds, J.P. Bollback, A. Rambaut, J. Penades, J.R. Fitzgerald, Genome Biology and Evolution 2 (2010) 454–466.","apa":"Guinane, C., Ben Zakour, N., Tormo Mas, M., Weinert, L., Lowder, B., Cartwright, R., … Fitzgerald, J. R. (2010). Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation. Genome Biology and Evolution. Oxford University Press. https://doi.org/10.1093/gbe/evq031"},"publication_status":"published"},{"publication_status":"published","citation":{"short":"J.P. Bollback, J. Huelsenbeck, Genetics 181 (2009) 225–234.","apa":"Bollback, J. P., & Huelsenbeck, J. (2009). Parallel genetic evolution within and between bacteriophage species of varying degrees of divergence. Genetics. Genetics Society of America. https://doi.org/10.1534/genetics.107.085225","ama":"Bollback JP, Huelsenbeck J. Parallel genetic evolution within and between bacteriophage species of varying degrees of divergence. Genetics. 2009;181(1):225-234. doi:10.1534/genetics.107.085225","mla":"Bollback, Jonathan P., and John Huelsenbeck. “Parallel Genetic Evolution within and between Bacteriophage Species of Varying Degrees of Divergence.” Genetics, vol. 181, no. 1, Genetics Society of America, 2009, pp. 225–34, doi:10.1534/genetics.107.085225.","ieee":"J. P. Bollback and J. Huelsenbeck, “Parallel genetic evolution within and between bacteriophage species of varying degrees of divergence,” Genetics, vol. 181, no. 1. Genetics Society of America, pp. 225–234, 2009.","chicago":"Bollback, Jonathan P, and John Huelsenbeck. “Parallel Genetic Evolution within and between Bacteriophage Species of Varying Degrees of Divergence.” Genetics. Genetics Society of America, 2009. https://doi.org/10.1534/genetics.107.085225.","ista":"Bollback JP, Huelsenbeck J. 2009. Parallel genetic evolution within and between bacteriophage species of varying degrees of divergence. Genetics. 181(1), 225–234."},"quality_controlled":0,"fulldoi":"https://doi.org/10.1534/genetics.107.085225","page":"225 - 234","volume":181,"date_created":"2018-12-11T12:08:26Z","type":"journal_article","date_updated":"2021-01-12T07:56:22Z","author":[{"first_name":"Jonathan P","orcid":"0000-0002-4624-4612","full_name":"Jonathan Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback"},{"full_name":"Huelsenbeck, John P","first_name":"John","last_name":"Huelsenbeck"}],"issue":"1","abstract":[{"text":"Parallel evolution is the acquisition of identical adaptive traits in independently evolving populations. Understanding whether the genetic changes underlying adaptation to a common selective environment are parallel within and between species is interesting because it sheds light on the degree of evolutionary constraints. If parallel evolution is perfect, then the implication is that forces such as functional constraints, epistasis, and pleiotropy play an important role in shaping the outcomes of adaptive evolution. In addition, population genetic theory predicts that the probability of parallel evolution will decline with an increase in the number of adaptive solutions-if a single adaptive solution exists, then parallel evolution will be observed among highly divergent species. For this reason, it is predicted that close relatives-which likely overlap more in the details of their adaptive solutions-will show more parallel evolution. By adapting three related bacteriophage species to a novel environment we find (1) a high rate of parallel genetic evolution at orthologous nucleotide and amino acid residues within species, (2) parallel beneficial mutations do not occur in a common order in which they fix or appear in an evolving population, (3) low rates of parallel evolution and convergent evolution between species, and (4) the probability of parallel and convergent evolution between species is strongly effected by divergence.","lang":"eng"}],"intvolume":" 181","month":"01","date_published":"2009-01-01T00:00:00Z","extern":1,"doi":"10.1534/genetics.107.085225","publisher":"Genetics Society of America","_id":"4357","day":"01","year":"2009","status":"public","publication":"Genetics","publist_id":"1101","title":"Parallel genetic evolution within and between bacteriophage species of varying degrees of divergence"},{"month":"05","date_published":"2008-05-01T00:00:00Z","abstract":[{"lang":"eng","text":"We develop a new method for estimating effective population sizes, Ne, and selection coefficients, s, from time-series data of allele frequencies sampled from a single diallelic locus. The method is based on calculating transition probabilities, using a numerical solution of the diffusion process, and assuming independent binomial sampling from this diffusion process at each time point. We apply the method in two example applications. First, we estimate selection coefficients acting on the CCR5-Δ32 mutation on the basis of published samples of contemporary and ancient human DNA. We show that the data are compatible with the assumption of s = 0, although moderate amounts of selection acting on this mutation cannot be excluded. In our second example, we estimate the selection coefficient acting on a mutation segregating in an experimental phage population. We show that the selection coefficient acting on this mutation is ~0.43."}],"intvolume":" 179","oa":1,"main_file_link":[{"open_access":"1","url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2390626"}],"extern":1,"_id":"3435","publisher":"Genetics Society of America","doi":"10.1534/genetics.107.085019","year":"2008","day":"01","title":"Estimation of 2Nes From Temporal Allele Frequency Data","status":"public","publication":"Genetics","publist_id":"2965","publication_status":"published","citation":{"ista":"Bollback JP, York T, Nielsen R. 2008. Estimation of 2Nes From Temporal Allele Frequency Data. Genetics. 179(1), 497–502.","mla":"Bollback, Jonathan P., et al. “Estimation of 2Nes From Temporal Allele Frequency Data.” Genetics, vol. 179, no. 1, Genetics Society of America, 2008, pp. 497–502, doi:10.1534/genetics.107.085019.","ama":"Bollback JP, York T, Nielsen R. Estimation of 2Nes From Temporal Allele Frequency Data. Genetics. 2008;179(1):497-502. doi:10.1534/genetics.107.085019","ieee":"J. P. Bollback, T. York, and R. Nielsen, “Estimation of 2Nes From Temporal Allele Frequency Data,” Genetics, vol. 179, no. 1. Genetics Society of America, pp. 497–502, 2008.","chicago":"Bollback, Jonathan P, Thomas York, and Rasmus Nielsen. “Estimation of 2Nes From Temporal Allele Frequency Data.” Genetics. Genetics Society of America, 2008. https://doi.org/10.1534/genetics.107.085019.","short":"J.P. Bollback, T. York, R. Nielsen, Genetics 179 (2008) 497–502.","apa":"Bollback, J. P., York, T., & Nielsen, R. (2008). Estimation of 2Nes From Temporal Allele Frequency Data. Genetics. Genetics Society of America. https://doi.org/10.1534/genetics.107.085019"},"quality_controlled":0,"fulldoi":"https://doi.org/10.1534/genetics.107.085019","volume":179,"date_created":"2018-12-11T12:03:19Z","page":"497 - 502","author":[{"orcid":"0000-0002-4624-4612","full_name":"Jonathan Bollback","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"York","first_name":"Thomas","full_name":"York, Thomas L"},{"full_name":"Nielsen, Rasmus","first_name":"Rasmus","last_name":"Nielsen"}],"issue":"1","type":"journal_article","date_updated":"2021-01-12T07:43:27Z"},{"volume":2,"date_created":"2018-12-11T12:08:25Z","author":[{"last_name":"Binladen","full_name":"Binladen, Jonas","first_name":"Jonas"},{"last_name":"Gilbert","full_name":"Gilbert, M Thomas","first_name":"M Thomas"},{"last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Jonathan Bollback","orcid":"0000-0002-4624-4612","first_name":"Jonathan P"},{"first_name":"Frank","full_name":"Panitz, Frank","last_name":"Panitz"},{"last_name":"Bendixen","full_name":"Bendixen, Christian","first_name":"Christian"},{"first_name":"Rasmus","full_name":"Nielsen, Rasmus","last_name":"Nielsen"},{"last_name":"Willerslev","full_name":"Willerslev, Eske","first_name":"Eske"}],"issue":"2","type":"journal_article","date_updated":"2021-01-12T07:56:21Z","quality_controlled":0,"fulldoi":"https://doi.org/10.1371/journal.pone.0000197","citation":{"apa":"Binladen, J., Gilbert, M. T., Bollback, J. P., Panitz, F., Bendixen, C., Nielsen, R., & Willerslev, E. (2007). The use of coded PCR primers enables high-throughput sequencing of multiple homolog amplification products by 454 parallel sequencing. PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0000197","short":"J. Binladen, M.T. Gilbert, J.P. Bollback, F. Panitz, C. Bendixen, R. Nielsen, E. Willerslev, PLoS One 2 (2007).","mla":"Binladen, Jonas, et al. “The Use of Coded PCR Primers Enables High-Throughput Sequencing of Multiple Homolog Amplification Products by 454 Parallel Sequencing.” PLoS One, vol. 2, no. 2, Public Library of Science, 2007, doi:10.1371/journal.pone.0000197.","ama":"Binladen J, Gilbert MT, Bollback JP, et al. The use of coded PCR primers enables high-throughput sequencing of multiple homolog amplification products by 454 parallel sequencing. PLoS One. 2007;2(2). doi:10.1371/journal.pone.0000197","ieee":"J. Binladen et al., “The use of coded PCR primers enables high-throughput sequencing of multiple homolog amplification products by 454 parallel sequencing,” PLoS One, vol. 2, no. 2. Public Library of Science, 2007.","chicago":"Binladen, Jonas, M Thomas Gilbert, Jonathan P Bollback, Frank Panitz, Christian Bendixen, Rasmus Nielsen, and Eske Willerslev. “The Use of Coded PCR Primers Enables High-Throughput Sequencing of Multiple Homolog Amplification Products by 454 Parallel Sequencing.” PLoS One. Public Library of Science, 2007. https://doi.org/10.1371/journal.pone.0000197.","ista":"Binladen J, Gilbert MT, Bollback JP, Panitz F, Bendixen C, Nielsen R, Willerslev E. 2007. The use of coded PCR primers enables high-throughput sequencing of multiple homolog amplification products by 454 parallel sequencing. PLoS One. 2(2)."},"publication_status":"published","year":"2007","day":"14","title":"The use of coded PCR primers enables high-throughput sequencing of multiple homolog amplification products by 454 parallel sequencing","publication":"PLoS One","status":"public","publist_id":"1105","publisher":"Public Library of Science","_id":"4353","acknowledgement":"JB and EW were supported by the Wellcome Trust, UK, the Carlsberg Foundation, DK, and the National Science Foundation, DK. MTPG acknowledges the Marie Curie Actions FP6-MEIF-CT-2005-025002 ‘FORMAPLEX’ grant for funding his research. JPB and RN were funded by the Danish FSS and the National Science Foundation, DK. None of the sponsors or funders have had any influence on the data or manuscript presented here.","doi":"10.1371/journal.pone.0000197","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"},"extern":1,"month":"02","date_published":"2007-02-14T00:00:00Z","intvolume":" 2","abstract":[{"lang":"eng","text":"BACKGROUND: The invention of the Genome Sequence 20 DNA Sequencing System (454 parallel sequencing platform) has enabled the rapid and high-volume production of sequence data. Until now, however, individual emulsion PCR (emPCR) reactions and subsequent sequencing runs have been unable to combine template DNA from multiple individuals, as homologous sequences cannot be subsequently assigned to their original sources. METHODOLOGY: We use conventional PCR with 5'-nucleotide tagged primers to generate homologous DNA amplification products from multiple specimens, followed by sequencing through the high-throughput Genome Sequence 20 DNA Sequencing System (GS20, Roche/454 Life Sciences). Each DNA sequence is subsequently traced back to its individual source through 5'tag-analysis. CONCLUSIONS: We demonstrate that this new approach enables the assignment of virtually all the generated DNA sequences to the correct source once sequencing anomalies are accounted for (miss-assignment rate<0.4%). Therefore, the method enables accurate sequencing and assignment of homologous DNA sequences from multiple sources in single high-throughput GS20 run. We observe a bias in the distribution of the differently tagged primers that is dependent on the 5' nucleotide of the tag. In particular, primers 5' labelled with a cytosine are heavily overrepresented among the final sequences, while those 5' labelled with a thymine are strongly underrepresented. A weaker bias also exists with regards to the distribution of the sequences as sorted by the second nucleotide of the dinucleotide tags. As the results are based on a single GS20 run, the general applicability of the approach requires confirmation. However, our experiments demonstrate that 5'primer tagging is a useful method in which the sequencing power of the GS20 can be applied to PCR-based assays of multiple homologous PCR products. The new approach will be of value to a broad range of research areas, such as those of comparative genomics, complete mitochondrial analyses, population genetics, and phylogenetics."}]},{"author":[{"full_name":"Freyhult, Eva K","first_name":"Eva","last_name":"Freyhult"},{"orcid":"0000-0002-4624-4612","full_name":"Jonathan Bollback","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Paul","full_name":"Gardner, Paul P","last_name":"Gardner"}],"issue":"1","date_updated":"2021-01-12T07:56:21Z","type":"journal_article","date_created":"2018-12-11T12:08:25Z","volume":17,"page":"117 - 25","fulldoi":"https://doi.org/10.1101/gr.5890907","quality_controlled":0,"citation":{"short":"E. Freyhult, J.P. Bollback, P. Gardner, Genome Research 17 (2007) 117–25.","apa":"Freyhult, E., Bollback, J. P., & Gardner, P. (2007). Exploring genomic dark matter: a critical assessment of the performance of homology search methods on noncoding RNA. Genome Research. Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/gr.5890907","ista":"Freyhult E, Bollback JP, Gardner P. 2007. Exploring genomic dark matter: a critical assessment of the performance of homology search methods on noncoding RNA. Genome Research. 17(1), 117–25.","chicago":"Freyhult, Eva, Jonathan P Bollback, and Paul Gardner. “Exploring Genomic Dark Matter: A Critical Assessment of the Performance of Homology Search Methods on Noncoding RNA.” Genome Research. Cold Spring Harbor Laboratory Press, 2007. https://doi.org/10.1101/gr.5890907.","ama":"Freyhult E, Bollback JP, Gardner P. Exploring genomic dark matter: a critical assessment of the performance of homology search methods on noncoding RNA. Genome Research. 2007;17(1):117-125. doi:10.1101/gr.5890907","ieee":"E. Freyhult, J. P. Bollback, and P. Gardner, “Exploring genomic dark matter: a critical assessment of the performance of homology search methods on noncoding RNA,” Genome Research, vol. 17, no. 1. Cold Spring Harbor Laboratory Press, pp. 117–25, 2007.","mla":"Freyhult, Eva, et al. “Exploring Genomic Dark Matter: A Critical Assessment of the Performance of Homology Search Methods on Noncoding RNA.” Genome Research, vol. 17, no. 1, Cold Spring Harbor Laboratory Press, 2007, pp. 117–25, doi:10.1101/gr.5890907."},"publication_status":"published","title":"Exploring genomic dark matter: a critical assessment of the performance of homology search methods on noncoding RNA","publication":"Genome Research","publist_id":"1106","status":"public","year":"2007","day":"01","_id":"4354","publisher":"Cold Spring Harbor Laboratory Press","doi":"10.1101/gr.5890907","extern":1,"main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1716261","open_access":"0"}],"month":"01","date_published":"2007-01-01T00:00:00Z","abstract":[{"text":"Homology search is one of the most ubiquitous bioinformatic tasks, yet it is unknown how effective the currently available tools are for identifying noncoding RNAs (ncRNAs). In this work, we use reliable ncRNA data sets to assess the effectiveness of methods such as BLAST, FASTA, HMMer, and Infernal. Surprisingly, the most popular homology search methods are often the least accurate. As a result, many studies have used inappropriate tools for their analyses. On the basis of our results, we suggest homology search strategies using the currently available tools and some directions for future development.","lang":"eng"}],"intvolume":" 17"}]