[{"day":"09","publication":"eLife","has_accepted_license":"1","isi":1,"year":"2018","date_published":"2018-03-09T00:00:00Z","doi":"10.7554/eLife.32035","date_created":"2018-12-11T11:46:23Z","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.","quality_controlled":"1","publisher":"eLife Sciences Publications","oa":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"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.","short":"P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, ELife 7 (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","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","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.","ista":"Payne P, Geyrhofer L, Barton NH, Bollback JP. 2018. CRISPR-based herd immunity can limit phage epidemics in bacterial populations. eLife. 7, e32035.","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."},"title":"CRISPR-based herd immunity can limit phage epidemics in bacterial populations","publist_id":"7400","author":[{"id":"35F78294-F248-11E8-B48F-1D18A9856A87","first_name":"Pavel","last_name":"Payne","full_name":"Payne, Pavel","orcid":"0000-0002-2711-9453"},{"first_name":"Lukas","full_name":"Geyrhofer, Lukas","last_name":"Geyrhofer"},{"full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","last_name":"Bollback"}],"external_id":{"isi":["000431035800001"]},"article_processing_charge":"No","article_number":"e32035","project":[{"_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440"}],"file":[{"creator":"dernst","file_size":3533881,"date_updated":"2020-07-14T12:46:25Z","file_name":"2018_eLife_Payne.pdf","date_created":"2018-12-17T10:36:07Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"5689","checksum":"447cf6e680bdc3c01062a8737d876569"}],"language":[{"iso":"eng"}],"publication_status":"published","related_material":{"record":[{"status":"public","id":"9840","relation":"research_data"}]},"volume":7,"ec_funded":1,"oa_version":"Published Version","abstract":[{"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.","lang":"eng"}],"month":"03","intvolume":" 7","scopus_import":"1","ddc":["576"],"date_updated":"2023-09-11T12:49:17Z","file_date_updated":"2020-07-14T12:46:25Z","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"_id":"423","status":"public","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"}},{"_id":"9840","status":"public","type":"research_data_reference","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","citation":{"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.","short":"P. Payne, L. Geyrhofer, N.H. Barton, J.P. Bollback, (2018).","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","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","mla":"Payne, Pavel, et al. Data from: CRISPR-Based Herd Immunity Limits Phage Epidemics in Bacterial Populations. Dryad, 2018, doi:10.5061/dryad.42n44.","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.","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."},"date_updated":"2023-09-11T12:49:17Z","title":"Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"author":[{"first_name":"Pavel","id":"35F78294-F248-11E8-B48F-1D18A9856A87","full_name":"Payne, Pavel","orcid":"0000-0002-2711-9453","last_name":"Payne"},{"full_name":"Geyrhofer, Lukas","last_name":"Geyrhofer","first_name":"Lukas"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H","last_name":"Barton"},{"first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P"}],"article_processing_charge":"No","oa_version":"Published Version","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."}],"month":"03","publisher":"Dryad","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.42n44"}],"day":"12","year":"2018","related_material":{"record":[{"relation":"used_in_publication","id":"423","status":"public"}]},"date_published":"2018-03-12T00:00:00Z","doi":"10.5061/dryad.42n44","date_created":"2021-08-09T13:10:02Z"},{"day":"10","publication":"Nature Ecology and Evolution","isi":1,"has_accepted_license":"1","year":"2018","date_published":"2018-09-10T00:00:00Z","doi":"10.1038/s41559-018-0651-y","date_created":"2018-12-11T11:44:27Z","page":"1633 - 1643","quality_controlled":"1","publisher":"Nature Publishing Group","oa":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"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.","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","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","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.","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2(10), 1633–1643.","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."},"title":"Evolutionary potential of transcription factors for gene regulatory rewiring","publist_id":"7987","author":[{"full_name":"Igler, Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia"},{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","full_name":"Lagator, Mato","last_name":"Lagator"},{"last_name":"Tkacik","full_name":"Tkacik, Gasper","orcid":"0000-0002-6699-1455","first_name":"Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","last_name":"Bollback"},{"last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"isi":["000447947600021"]},"article_processing_charge":"No","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer"},{"_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)","grant_number":"24573"}],"file":[{"checksum":"383a2e2c944a856e2e821ec8e7bf71b6","file_id":"7830","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2018_NatureEcology_Igler.pdf","date_created":"2020-05-14T11:28:52Z","creator":"dernst","file_size":1135973,"date_updated":"2020-07-14T12:47:37Z"}],"language":[{"iso":"eng"}],"publication_status":"published","volume":2,"related_material":{"record":[{"id":"5585","status":"public","relation":"popular_science"},{"relation":"dissertation_contains","id":"6371","status":"public"}]},"issue":"10","ec_funded":1,"oa_version":"Submitted Version","abstract":[{"lang":"eng","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."}],"month":"09","intvolume":" 2","scopus_import":"1","ddc":["570"],"date_updated":"2024-03-27T23:30:48Z","file_date_updated":"2020-07-14T12:47:37Z","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"JoBo"}],"_id":"67","status":"public","type":"journal_article","article_type":"original"},{"publication_status":"published","publication_identifier":{"issn":["2050084X"]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"5096","checksum":"273ab17f33305e4eaafd911ff88e7c5b","date_updated":"2020-07-14T12:47:10Z","file_size":8453470,"creator":"system","date_created":"2018-12-12T10:14:42Z","file_name":"IST-2017-918-v1+1_elife-28921-figures-v3.pdf"},{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"5097","checksum":"b433f90576c7be597cd43367946f8e7f","date_updated":"2020-07-14T12:47:10Z","file_size":1953221,"creator":"system","date_created":"2018-12-12T10:14:43Z","file_name":"IST-2017-918-v1+2_elife-28921-v3.pdf"}],"ec_funded":1,"volume":6,"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. "}],"oa_version":"Published Version","scopus_import":1,"intvolume":" 6","month":"11","date_updated":"2021-01-12T08:03:15Z","ddc":["576"],"file_date_updated":"2020-07-14T12:47:10Z","department":[{"_id":"CaGu"},{"_id":"JoBo"},{"_id":"NiBa"}],"_id":"570","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","pubrep_id":"918","status":"public","year":"2017","has_accepted_license":"1","publication":"eLife","day":"13","date_created":"2018-12-11T11:47:14Z","date_published":"2017-11-13T00:00:00Z","doi":"10.7554/eLife.28921","oa":1,"quality_controlled":"1","publisher":"eLife Sciences Publications","citation":{"ista":"Lagator M, Sarikas S, Acar H, Bollback JP, Guet CC. 2017. Regulatory network structure determines patterns of intermolecular epistasis. eLife. 6, e28921.","chicago":"Lagator, Mato, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, and Calin C Guet. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.28921.","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","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).","ieee":"M. Lagator, S. Sarikas, H. Acar, J. P. Bollback, and C. C. Guet, “Regulatory network structure determines patterns of intermolecular epistasis,” eLife, vol. 6. eLife Sciences Publications, 2017.","mla":"Lagator, Mato, et al. “Regulatory Network Structure Determines Patterns of Intermolecular Epistasis.” ELife, vol. 6, e28921, eLife Sciences Publications, 2017, doi:10.7554/eLife.28921."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publist_id":"7244","author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"last_name":"Sarikas","full_name":"Sarikas, Srdjan","first_name":"Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Hande","id":"2DDF136A-F248-11E8-B48F-1D18A9856A87","full_name":"Acar, Hande","orcid":"0000-0003-1986-9753","last_name":"Acar"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","last_name":"Bollback"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet"}],"title":"Regulatory network structure determines patterns of intermolecular epistasis","article_number":"e28921","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425"}]},{"page":"83","date_published":"2017-02-01T00:00:00Z","date_created":"2019-04-09T15:16:45Z","has_accepted_license":"1","publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","year":"2017","file":[{"relation":"main_file","access_level":"closed","content_type":"application/pdf","checksum":"a0fc5c26a89c0ea759947ffba87d0d8f","file_id":"6292","creator":"dernst","file_size":3025175,"date_updated":"2020-07-14T12:47:27Z","file_name":"thesis_pavel_payne_final_w_signature_page.pdf","date_created":"2019-04-09T15:15:32Z"},{"creator":"dernst","file_size":3111536,"date_updated":"2021-02-22T13:45:59Z","file_name":"2017_Payne_Thesis.pdf","date_created":"2021-02-22T13:45:59Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"checksum":"af531e921a7f64a9e0af4cd8783b2226","file_id":"9187"}],"day":"01","language":[{"iso":"eng"}],"alternative_title":["ISTA Thesis"],"publisher":"Institute of Science and Technology Austria","oa":1,"month":"02","abstract":[{"lang":"eng","text":"Bacteria and their pathogens – phages – are the most abundant living entities on Earth. Throughout their coevolution, bacteria have evolved multiple immune systems to overcome the ubiquitous threat from the phages. Although the molecu- lar details of these immune systems’ functions are relatively well understood, their epidemiological consequences for the phage-bacterial communities have been largely neglected. In this thesis we employed both experimental and theoretical methods to explore whether herd and social immunity may arise in bacterial popu- lations. Using our experimental system consisting of Escherichia coli strains with a CRISPR based immunity to the T7 phage we show that herd immunity arises in phage-bacterial communities and that it is accentuated when the populations are spatially structured. By fitting a mathematical model, we inferred expressions for the herd immunity threshold and the velocity of spread of a phage epidemic in partially resistant bacterial populations, which both depend on the bacterial growth rate, phage burst size and phage latent period. We also investigated the poten- tial for social immunity in Streptococcus thermophilus and its phage 2972 using a bioinformatic analysis of potentially coding short open reading frames with a signalling signature, encoded within the CRISPR associated genes. Subsequently, we tested one identified potentially signalling peptide and found that its addition to a phage-challenged culture increases probability of survival of bacteria two fold, although the results were only marginally significant. Together, these results demonstrate that the ubiquitous arms races between bacteria and phages have further consequences at the level of the population."}],"oa_version":"Published Version","author":[{"orcid":"0000-0002-2711-9453","full_name":"Payne, Pavel","last_name":"Payne","first_name":"Pavel","id":"35F78294-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"title":"Bacterial herd and social immunity to phages","file_date_updated":"2021-02-22T13:45:59Z","supervisor":[{"last_name":"Bollback","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H","last_name":"Barton","first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-07T12:00:00Z","citation":{"mla":"Payne, Pavel. Bacterial Herd and Social Immunity to Phages. Institute of Science and Technology Austria, 2017.","ama":"Payne P. Bacterial herd and social immunity to phages. 2017.","apa":"Payne, P. (2017). Bacterial herd and social immunity to phages. Institute of Science and Technology Austria.","short":"P. Payne, Bacterial Herd and Social Immunity to Phages, Institute of Science and Technology Austria, 2017.","ieee":"P. Payne, “Bacterial herd and social immunity to phages,” Institute of Science and Technology Austria, 2017.","chicago":"Payne, Pavel. “Bacterial Herd and Social Immunity to Phages.” Institute of Science and Technology Austria, 2017.","ista":"Payne P. 2017. Bacterial herd and social immunity to phages. Institute of Science and Technology Austria."},"ddc":["570"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","type":"dissertation","status":"public","_id":"6291"},{"ec_funded":1,"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"c62257a7bff0c5f39e1abffc6bfcca5c","file_id":"5252","date_updated":"2020-07-14T12:48:10Z","file_size":3417773,"creator":"system","date_created":"2018-12-12T10:17:00Z","file_name":"IST-2017-857-v1+1_thesis_fabienne.pdf"},{"creator":"dernst","file_size":215899,"date_updated":"2020-07-14T12:48:10Z","file_name":"2017_thesis_Jesse_source.tex","date_created":"2019-04-05T08:51:59Z","relation":"source_file","access_level":"closed","content_type":"application/x-tex","checksum":"fc87d7d72fce52824a3ae7dcad0413a8","file_id":"6212"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"publication_status":"published","degree_awarded":"PhD","month":"08","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"text":"The lac operon is a classic model system for bacterial gene regulation, and has been studied extensively in E. coli, a classic model organism. However, not much is known about E. coli’s ecology and life outside the laboratory, in particular in soil and water environments. The natural diversity of the lac operon outside the laboratory, its role in the ecology of E. coli and the selection pressures it is exposed to, are similarly unknown.\r\nIn Chapter Two of this thesis, I explore the genetic diversity, phylogenetic history and signatures of selection of the lac operon across 20 natural isolates of E. coli and divergent clades of Escherichia. I found that complete lac operons were present in all isolates examined, which in all but one case were functional. The lac operon phylogeny conformed to the whole-genome phylogeny of the divergent Escherichia clades, which excludes horizontal gene transfer as an explanation for the presence of functional lac operons in these clades. All lac operon genes showed a signature of purifying selection; this signature was strongest for the lacY gene. Lac operon genes of human and environmental isolates showed similar signatures of selection, except the lacZ gene, which showed a stronger signature of selection in environmental isolates.\r\nIn Chapter Three, I try to identify the natural genetic variation relevant for phenotype and fitness in the lac operon, comparing growth rate on lactose and LacZ activity of the lac operons of these wild isolates in a common genetic background. Sequence variation in the lac promoter region, upstream of the -10 and -35 RNA polymerase binding motif, predicted variation in LacZ activity at full induction, using a thermodynamic model of polymerase binding (Tugrul, 2016). However, neither variation in LacZ activity, nor RNA polymerase binding predicted by the model correlated with variation in growth rate. Lac operons of human and environmental isolates did not differ systematically in either growth rate on lactose or LacZ protein activity, suggesting that these lac operons have been exposed to similar selection pressures. We thus have no evidence that the phenotypic variation we measured is relevant for fitness.\r\nTo start assessing the effect of genomic background on the growth phenotype conferred by the lac operon, I compared growth on minimal medium with lactose between lac operon constructs and the corresponding original isolates, I found that maximal growth rate was determined by genomic background, with almost all backgrounds conferring higher growth rates than lab strain K12 MG1655. However, I found no evidence that the lactose concentration at which growth was half maximal depended on genomic background.","lang":"eng"}],"file_date_updated":"2020-07-14T12:48:10Z","department":[{"_id":"JoBo"}],"ddc":["576","577","579"],"supervisor":[{"orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","last_name":"Bollback","first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-07T12:01:21Z","status":"public","pubrep_id":"857","type":"dissertation","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"820","doi":"10.15479/AT:ISTA:th_857","date_published":"2017-08-25T00:00:00Z","date_created":"2018-12-11T11:48:41Z","page":"87","day":"25","has_accepted_license":"1","year":"2017","publisher":"Institute of Science and Technology Austria","oa":1,"acknowledgement":"ERC H2020 programme (grant agreement no. 648440)\r\nThanks to Jon Bollback for giving me the chance to do this work, for sharing the ideas that lay at the basis of this work, for his honesty and openness, showing himself to me as a person and not just as a boss. Thanks to Nick Barton for his guidance at the last stage, reading and commenting extensively on several versions of this manuscript, and for his encouragement; thanks to both Jon and Nick for their kindness and patience. Thanks to Erik van Nimwegen and Calin Guet for their time and willingness to be in my thesis committee, and to Erik van Nimwegen especially for agreeing to enter my thesis committee at the last moment, and for his very sharp, helpful and relevant comments during and after the defense. Thanks to my collaborators and discussion partners: Anne Kupczok, for her guidance, ideas and discussions during the construction of the manuscript of Chapter Two, and her comments on the manuscript; Georg Rieckh for making me aware of the issue of parameter identifiability, suggesting how to solve it, and for his unfortunate idea to start the plasmid enterprise in the first place; Murat Tugrul for sharing his model, for his enthusiasm, and his comments on Chapter Three; Srdjan Sarikas for his collaboration on the Monod model fitting, fast forwarding the analysis to turbo speed and making beautiful figures, and making the discussion fun on top of it all; Vanessa Barone for her last minute comments, especially on Chapter Three, providing a sharp and very helpful experimentalist perspective at the last moment; Maros Pleska and Marjon de Vos for their comments on the manuscript of Chapter Two; Gasper Tkacik for his crucial input on the relation between growth rate and lactose concentration; Bor Kavcic for his input on growth rate modeling and error propagation. Thanks to the Bollback, Bollenbach, Barton, Guet and Tkacik group members for both pro- viding an inspiring and supportive scientific environment to work in, as well as a lot of warmth and colour to everyday life. And thanks to the friends I found here, to the people who were there for me and to the people who changed my life, making it stranger and more beautiful than I could have imagined, Maros, Vanessa, Tade, Suzi, Andrej, Peter, Tiago, Kristof, Karin, Irene, Misha, Mato, Guillaume and Zanin. ","title":"The lac operon in the wild","publist_id":"6829","author":[{"full_name":"Jesse, Fabienne","last_name":"Jesse","id":"4C8C26A4-F248-11E8-B48F-1D18A9856A87","first_name":"Fabienne"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Jesse, Fabienne. “The Lac Operon in the Wild.” Institute of Science and Technology Austria, 2017. https://doi.org/10.15479/AT:ISTA:th_857.","ista":"Jesse F. 2017. The lac operon in the wild. Institute of Science and Technology Austria.","mla":"Jesse, Fabienne. The Lac Operon in the Wild. Institute of Science and Technology Austria, 2017, doi:10.15479/AT:ISTA:th_857.","short":"F. Jesse, The Lac Operon in the Wild, Institute of Science and Technology Austria, 2017.","ieee":"F. Jesse, “The lac operon in the wild,” Institute of Science and Technology Austria, 2017.","ama":"Jesse F. The lac operon in the wild. 2017. doi:10.15479/AT:ISTA:th_857","apa":"Jesse, F. (2017). The lac operon in the wild. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_857"},"project":[{"call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440"}]},{"ddc":["570"],"date_updated":"2023-09-20T11:56:34Z","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"file_date_updated":"2019-01-18T09:14:02Z","_id":"1077","status":"public","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"file":[{"file_name":"2017_JRSI_Redondo.pdf","date_created":"2019-01-18T09:14:02Z","creator":"dernst","file_size":1092015,"date_updated":"2019-01-18T09:14:02Z","success":1,"file_id":"5843","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["17425689"]},"publication_status":"published","issue":"126","volume":14,"related_material":{"record":[{"id":"9864","status":"public","relation":"research_data"}]},"ec_funded":1,"oa_version":"Published Version","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 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."}],"month":"01","intvolume":" 14","scopus_import":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"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 of London, 2017. https://doi.org/10.1098/rsif.2016.0139.","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 of London, 2017, doi: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).","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 of London, 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 of London. https://doi.org/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"},"title":"Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family","author":[{"first_name":"Rodrigo A","id":"409D5C96-F248-11E8-B48F-1D18A9856A87","last_name":"Fernandes Redondo","full_name":"Fernandes Redondo, Rodrigo A","orcid":"0000-0002-5837-2793"},{"orcid":"0000-0002-5985-7653","full_name":"Vladar, Harold","last_name":"Vladar","id":"2A181218-F248-11E8-B48F-1D18A9856A87","first_name":"Harold"},{"first_name":"Tomasz","last_name":"Włodarski","full_name":"Włodarski, Tomasz"},{"last_name":"Bollback","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P"}],"publist_id":"6303","external_id":{"isi":["000393380400001"]},"article_processing_charge":"Yes (in subscription journal)","article_number":"20160139","project":[{"grant_number":"250152","name":"Limits to selection in biology and in evolutionary computation","_id":"25B07788-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"day":"04","publication":"Journal of the Royal Society Interface","isi":1,"has_accepted_license":"1","year":"2017","date_published":"2017-01-04T00:00:00Z","doi":"10.1098/rsif.2016.0139","date_created":"2018-12-11T11:50:01Z","publisher":"Royal Society of London","quality_controlled":"1","oa":1},{"quality_controlled":"1","publisher":"eLife Sciences Publications","oa":1,"isi":1,"has_accepted_license":"1","year":"2017","day":"18","publication":"eLife","date_published":"2017-05-18T00:00:00Z","doi":"10.7554/eLife.25192","date_created":"2018-12-11T11:49:23Z","article_number":"e25192","project":[{"grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"},{"_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440"}],"citation":{"chicago":"Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192.","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.","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.","short":"M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017).","apa":"Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192","ama":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 2017;6. doi:10.7554/eLife.25192"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publist_id":"6460","author":[{"first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato","last_name":"Lagator"},{"last_name":"Paixao","full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago"},{"orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H"},{"last_name":"Bollback","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"article_processing_charge":"Yes","external_id":{"isi":["000404024800001"]},"title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","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."}],"oa_version":"Published Version","scopus_import":"1","month":"05","intvolume":" 6","publication_identifier":{"issn":["2050084X"]},"publication_status":"published","file":[{"creator":"system","date_updated":"2020-07-14T12:48:16Z","file_size":2441529,"date_created":"2018-12-12T10:17:49Z","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"59cdd4400fb41280122d414fea971546","file_id":"5306"},{"file_name":"IST-2017-841-v1+2_elife-25192-figures-v2.pdf","date_created":"2018-12-12T10:17:50Z","file_size":3752660,"date_updated":"2020-07-14T12:48:16Z","creator":"system","file_id":"5307","checksum":"b69024880558b858eb8c5d47a92b6377","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"volume":6,"ec_funded":1,"_id":"954","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","pubrep_id":"841","date_updated":"2023-09-22T10:01:17Z","ddc":["576"],"department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"file_date_updated":"2020-07-14T12:48:16Z"},{"ec_funded":1,"volume":33,"issue":"3","publication_status":"published","language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"1f456ce1d2aa2f67176a1709f9702ecf","file_id":"4751","date_updated":"2020-07-14T12:44:53Z","file_size":648115,"creator":"system","date_created":"2018-12-12T10:09:27Z","file_name":"IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf"}],"scopus_import":1,"intvolume":" 33","month":"03","abstract":[{"lang":"eng","text":"Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner."}],"oa_version":"Published Version","file_date_updated":"2020-07-14T12:44:53Z","department":[{"_id":"CaGu"},{"_id":"JoBo"}],"date_updated":"2021-01-12T06:50:39Z","ddc":["570","576"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","pubrep_id":"588","status":"public","_id":"1427","page":"761 - 769","date_created":"2018-12-11T11:51:57Z","doi":"10.1093/molbev/msv269","date_published":"2016-03-01T00:00:00Z","year":"2016","has_accepted_license":"1","publication":"Molecular Biology and Evolution","day":"01","oa":1,"quality_controlled":"1","publisher":"Oxford University Press","author":[{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator","full_name":"Lagator, Mato"},{"last_name":"Igler","full_name":"Igler, Claudia","first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Anaisa","last_name":"Moreno","full_name":"Moreno, Anaisa"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","last_name":"Bollback"}],"publist_id":"5772","title":"Epistatic interactions in the arabinose cis-regulatory element","citation":{"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.","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.","short":"M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769.","apa":"Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016). Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269","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"},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"}]},{"month":"12","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"text":"Horizontal gene transfer (HGT), the lateral acquisition of genes across existing species\r\nboundaries, is a major evolutionary force shaping microbial genomes that facilitates\r\nadaptation to new environments as well as resistance to antimicrobial drugs. As such,\r\nunderstanding the mechanisms and constraints that determine the outcomes of HGT\r\nevents is crucial to understand the dynamics of HGT and to design better strategies to\r\novercome the challenges that originate from it.\r\nFollowing the insertion and expression of a newly transferred gene, the success of an\r\nHGT event will depend on the fitness effect it has on the recipient (host) cell. Therefore,\r\npredicting the impact of HGT on the genetic composition of a population critically\r\ndepends on the distribution of fitness effects (DFE) of horizontally transferred genes.\r\nHowever, to date, we have little knowledge of the DFE of newly transferred genes, and\r\nhence little is known about the shape and scale of this distribution.\r\nIt is particularly important to better understand the selective barriers that determine\r\nthe fitness effects of newly transferred genes. In spite of substantial bioinformatics\r\nefforts to identify horizontally transferred genes and selective barriers, a systematic\r\nexperimental approach to elucidate the roles of different selective barriers in defining\r\nthe fate of a transfer event has largely been absent. Similarly, although the fact that\r\nenvironment might alter the fitness effect of a horizontally transferred gene may seem\r\nobvious, little attention has been given to it in a systematic experimental manner.\r\nIn this study, we developed a systematic experimental approach that consists of\r\ntransferring 44 arbitrarily selected Salmonella typhimurium orthologous genes into an\r\nEscherichia coli host, and estimating the fitness effects of these transferred genes at a\r\nconstant expression level by performing competition assays against the wild type.\r\nIn chapter 2, we performed one-to-one competition assays between a mutant strain\r\ncarrying a transferred gene and the wild type strain. By using flow cytometry we\r\nestimated selection coefficients for the transferred genes with a precision level of 10-3,and obtained the DFE of horizontally transferred genes. We then investigated if these\r\nfitness effects could be predicted by any of the intrinsic properties of the genes, namely,\r\nfunctional category, degree of complexity (protein-protein interactions), GC content,\r\ncodon usage and length. Our analyses revealed that the functional category and length\r\nof the genes act as potential selective barriers. Finally, using the same procedure with\r\nthe endogenous E. coli orthologs of these 44 genes, we demonstrated that gene dosage is\r\nthe most prominent selective barrier to HGT.\r\nIn chapter 3, using the same set of genes we investigated the role of environment on the\r\nsuccess of HGT events. Under six different environments with different levels of stress\r\nwe performed more complex competition assays, where we mixed all 44 mutant strains\r\ncarrying transferred genes with the wild type strain. To estimate the fitness effects of\r\ngenes relative to wild type we used next generation sequencing. We found that the DFEs\r\nof horizontally transferred genes are highly dependent on the environment, with\r\nabundant gene–by-environment interactions. Furthermore, we demonstrated a\r\nrelationship between average fitness effect of a gene across all environments and its\r\nenvironmental variance, and thus its predictability. Finally, in spite of the fitness effects\r\nof genes being highly environment-dependent, we still observed a common shape of\r\nDFEs across all tested environments.","lang":"eng"}],"ec_funded":1,"language":[{"iso":"eng"}],"file":[{"file_id":"6814","checksum":"94bbbc754c36115bf37f8fc11fad43c4","content_type":"application/pdf","relation":"main_file","access_level":"closed","file_name":"PhDThesis_HandeAcar_1230.pdf","date_created":"2019-08-13T11:17:50Z","file_size":3682711,"date_updated":"2019-08-13T11:17:50Z","creator":"dernst"},{"creator":"dernst","file_size":3682711,"date_updated":"2021-02-22T11:51:13Z","file_name":"2016_Thesis_HandeAcar.pdf","date_created":"2021-02-22T11:51:13Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_id":"9184","checksum":"94bbbc754c36115bf37f8fc11fad43c4"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"status":"public","type":"dissertation","_id":"1121","department":[{"_id":"JoBo"}],"file_date_updated":"2021-02-22T11:51:13Z","ddc":["570"],"date_updated":"2023-09-07T11:42:26Z","supervisor":[{"orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P"}],"oa":1,"publisher":"Institute of Science and Technology Austria","acknowledgement":"This study was supported by European Research Council ERC CoG 2014 – EVOLHGT,\r\nunder the grant number 648440.\r\n\r\nIt is a pleasure to thank the many people who made this thesis possible.\r\nI would like to first thank my advisor, Jonathan Paul Bollback for providing guidance in\r\nall aspects of my life, encouragement, sound advice, and good teaching over the last six\r\nyears.\r\nI would also like to thank the members of my dissertation committee – Călin C. Guet\r\nand John F. Baines – not only for their time and guidance, but for their intellectual\r\ncontributions to my development as a scientist.\r\nI would like to thank Flavia Gama and Rodrigo Redondo who have taught me all the\r\nskills in the laboratory with their graciousness and friendship. Also special thanks to\r\nBollback group for their support and for providing a stimulating and fun environment:\r\nIsabella Tomanek, Fabienne Jesse, Claudia Igler, and Pavel Payne.\r\nJerneja Beslagic is not only an amazing assistant, she also has a smile brighter and\r\nwarmer than the sunshine, bringing happiness to every moment. Always keep your light\r\nNeja, I will miss our invaluable chatters a lot.","date_created":"2018-12-11T11:50:16Z","date_published":"2016-12-01T00:00:00Z","page":"75","day":"01","year":"2016","has_accepted_license":"1","project":[{"grant_number":"648440","name":"Selective Barriers to Horizontal Gene Transfer","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"title":"Selective barriers to horizontal gene transfer","article_processing_charge":"No","author":[{"id":"2DDF136A-F248-11E8-B48F-1D18A9856A87","first_name":"Hande","full_name":"Acar, Hande","orcid":"0000-0003-1986-9753","last_name":"Acar"}],"publist_id":"6239","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Acar, Hande. Selective Barriers to Horizontal Gene Transfer. Institute of Science and Technology Austria, 2016.","apa":"Acar, H. (2016). Selective barriers to horizontal gene transfer. Institute of Science and Technology Austria.","ama":"Acar H. Selective barriers to horizontal gene transfer. 2016.","ieee":"H. Acar, “Selective barriers to horizontal gene transfer,” Institute of Science and Technology Austria, 2016.","short":"H. Acar, Selective Barriers to Horizontal Gene Transfer, Institute of Science and Technology Austria, 2016.","chicago":"Acar, Hande. “Selective Barriers to Horizontal Gene Transfer.” Institute of Science and Technology Austria, 2016.","ista":"Acar H. 2016. Selective barriers to horizontal gene transfer. Institute of Science and Technology Austria."}},{"month":"12","main_file_link":[{"url":"https://doi.org/10.6084/m9.figshare.4315652.v1","open_access":"1"}],"oa":1,"publisher":"The Royal Society","oa_version":"Published Version","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."}],"date_created":"2021-08-10T08:29:47Z","doi":"10.6084/m9.figshare.4315652.v1","related_material":{"record":[{"id":"1077","status":"public","relation":"used_in_publication"}]},"date_published":"2016-12-14T00:00:00Z","day":"14","year":"2016","status":"public","type":"research_data_reference","_id":"9864","title":"Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"article_processing_charge":"No","author":[{"last_name":"Fernandes Redondo","orcid":"0000-0002-5837-2793","full_name":"Fernandes Redondo, Rodrigo A","id":"409D5C96-F248-11E8-B48F-1D18A9856A87","first_name":"Rodrigo A"},{"last_name":"de Vladar","full_name":"de Vladar, Harold","orcid":"0000-0002-5985-7653","id":"2A181218-F248-11E8-B48F-1D18A9856A87","first_name":"Harold"},{"full_name":"Włodarski, Tomasz","last_name":"Włodarski","first_name":"Tomasz"},{"last_name":"Bollback","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","citation":{"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","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","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.","short":"R.A. Fernandes Redondo, H. de Vladar, T. Włodarski, J.P. Bollback, (2016).","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.","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.","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."},"date_updated":"2023-09-20T11:56:33Z"},{"has_accepted_license":"1","year":"2016","datarep_id":"43","file":[{"creator":"system","file_size":1123495,"date_updated":"2020-07-14T12:47:01Z","file_name":"IST-2016-43-v1+1_DATA_MTugrul_PhDThesis_Chapter3.zip","date_created":"2018-12-12T13:03:08Z","relation":"main_file","access_level":"open_access","content_type":"application/zip","file_id":"5626","checksum":"1fc0a10bb7ce110fcb5e1fbe3cf0c4e2"}],"day":"12","related_material":{"record":[{"id":"1131","status":"public","relation":"used_in_publication"}]},"doi":"10.15479/AT:ISTA:43","date_published":"2016-05-12T00:00:00Z","license":"https://creativecommons.org/publicdomain/zero/1.0/","contributor":[{"first_name":"Magdalena","contributor_type":"researcher","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","last_name":"Steinrück"},{"id":"4C8C26A4-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","first_name":"Fabienne","last_name":"Jesse"}],"date_created":"2018-12-12T12:31:30Z","abstract":[{"lang":"eng","text":"The data stored here is used in Murat Tugrul's PhD thesis (Chapter 3), which is related to the evolution of bacterial RNA polymerase binding.\r\nMagdalena Steinrueck (PhD Student in Calin Guet's group at IST Austria) performed the experiments and created the data on de novo promoter evolution. Fabienne Jesse (PhD Student in Jon Bollback's group at IST Austria) performed the experiments and created the data on lac promoter evolution."}],"oa_version":"Published Version","publisher":"Institute of Science and Technology Austria","oa":1,"month":"05","citation":{"mla":"Tugrul, Murat. Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase. Institute of Science and Technology Austria, 2016, doi:10.15479/AT:ISTA:43.","ama":"Tugrul M. Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase. 2016. doi:10.15479/AT:ISTA:43","apa":"Tugrul, M. (2016). Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:43","short":"M. Tugrul, (2016).","ieee":"M. Tugrul, “Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase.” Institute of Science and Technology Austria, 2016.","chicago":"Tugrul, Murat. “Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase.” Institute of Science and Technology Austria, 2016. https://doi.org/10.15479/AT:ISTA:43.","ista":"Tugrul M. 2016. Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase, Institute of Science and Technology Austria, 10.15479/AT:ISTA:43."},"date_updated":"2024-02-21T13:50:34Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"id":"37C323C6-F248-11E8-B48F-1D18A9856A87","first_name":"Murat","full_name":"Tugrul, Murat","orcid":"0000-0002-8523-0758","last_name":"Tugrul"}],"article_processing_charge":"No","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"title":"Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase","file_date_updated":"2020-07-14T12:47:01Z","_id":"5554","type":"research_data","tmp":{"image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)","short":"CC0 (1.0)"},"status":"public","keyword":["RNAP binding","de novo promoter evolution","lac promoter"]},{"abstract":[{"text":"In the 1960s-1980s, determination of bacterial growth rates was an important tool in microbial genetics, biochemistry, molecular biology, and microbial physiology. The exciting technical developments of the 1990s and the 2000s eclipsed that tool; as a result, many investigators today lack experience with growth rate measurements. Recently, investigators in a number of areas have started to use measurements of bacterial growth rates for a variety of purposes. Those measurements have been greatly facilitated by the availability of microwell plate readers that permit the simultaneous measurements on up to 384 different cultures. Only the exponential (logarithmic) portions of the resulting growth curves are useful for determining growth rates, and manual determination of that portion and calculation of growth rates can be tedious for high-throughput purposes. Here, we introduce the program GrowthRates that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase. GrowthRates is freely available for Macintosh, Windows, and Linux.We discuss the effects of culture volume, the classical bacterial growth curve, and the differences between determinations in rich media and minimal (mineral salts) media. This protocol covers calibration of the plate reader, growth of culture inocula for both rich and minimal media, and experimental setup. As a guide to reliability, we report typical day-to-day variation in growth rates and variation within experiments with respect to position of wells within the plates.","lang":"eng"}],"oa_version":"None","pmid":1,"scopus_import":"1","intvolume":" 31","month":"01","publication_status":"published","publication_identifier":{"issn":["0737-4038"],"eissn":["1537-1719"]},"language":[{"iso":"eng"}],"volume":31,"issue":"1","_id":"1902","article_type":"original","type":"journal_article","status":"public","date_updated":"2022-06-07T11:08:13Z","department":[{"_id":"JoBo"}],"quality_controlled":"1","publisher":"Oxford University Press","year":"2014","publication":"Molecular Biology and Evolution","day":"01","page":"232 - 238","date_created":"2018-12-11T11:54:37Z","doi":"10.1093/molbev/mst187","date_published":"2014-01-01T00:00:00Z","citation":{"chicago":"Hall, Barry, Hande Acar, Anna Nandipati, and Miriam Barlow. “Growth Rates Made Easy.” Molecular Biology and Evolution. Oxford University Press, 2014. https://doi.org/10.1093/molbev/mst187.","ista":"Hall B, Acar H, Nandipati A, Barlow M. 2014. Growth rates made easy. Molecular Biology and Evolution. 31(1), 232–238.","mla":"Hall, Barry, et al. “Growth Rates Made Easy.” Molecular Biology and Evolution, vol. 31, no. 1, Oxford University Press, 2014, pp. 232–38, doi:10.1093/molbev/mst187.","short":"B. Hall, H. Acar, A. Nandipati, M. Barlow, Molecular Biology and Evolution 31 (2014) 232–238.","ieee":"B. Hall, H. Acar, A. Nandipati, and M. Barlow, “Growth rates made easy,” Molecular Biology and Evolution, vol. 31, no. 1. Oxford University Press, pp. 232–238, 2014.","ama":"Hall B, Acar H, Nandipati A, Barlow M. Growth rates made easy. Molecular Biology and Evolution. 2014;31(1):232-238. doi:10.1093/molbev/mst187","apa":"Hall, B., Acar, H., Nandipati, A., & Barlow, M. (2014). Growth rates made easy. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/mst187"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","external_id":{"pmid":["24170494"]},"publist_id":"5193","author":[{"first_name":"Barry","full_name":"Hall, Barry","last_name":"Hall"},{"first_name":"Hande","id":"2DDF136A-F248-11E8-B48F-1D18A9856A87","full_name":"Acar, Hande","orcid":"0000-0003-1986-9753","last_name":"Acar"},{"first_name":"Anna","last_name":"Nandipati","full_name":"Nandipati, Anna"},{"full_name":"Barlow, Miriam","last_name":"Barlow","first_name":"Miriam"}],"title":"Growth rates made easy"},{"publisher":"BioMed Central","quality_controlled":"1","oa":1,"date_published":"2014-08-08T00:00:00Z","doi":"10.1186/1471-2164-15-663","date_created":"2018-12-11T11:55:23Z","day":"08","publication":"BMC Genomics","has_accepted_license":"1","year":"2014","article_number":"663","title":"Motif depletion in bacteriophages infecting hosts with CRISPR systems","publist_id":"5009","author":[{"first_name":"Anne","id":"2BB22BC2-F248-11E8-B48F-1D18A9856A87","full_name":"Kupczok, Anne","last_name":"Kupczok"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P","last_name":"Bollback","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P"}],"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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","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","short":"A. Kupczok, J.P. Bollback, BMC Genomics 15 (2014).","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.","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.","ista":"Kupczok A, Bollback JP. 2014. Motif depletion in bacteriophages infecting hosts with CRISPR systems. BMC Genomics. 15(1), 663."},"month":"08","intvolume":" 15","scopus_import":1,"oa_version":"Published Version","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"}],"issue":"1","volume":15,"file":[{"date_updated":"2020-07-14T12:45:26Z","file_size":1489769,"creator":"system","date_created":"2018-12-12T10:11:24Z","file_name":"IST-2015-396-v1+1_1471-2164-15-663.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"3f6d2776b90a842a28359cc957d3d04b","file_id":"4878"}],"language":[{"iso":"eng"}],"publication_status":"published","status":"public","pubrep_id":"396","type":"journal_article","tmp":{"image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","name":"Creative Commons Public Domain Dedication (CC0 1.0)","short":"CC0 (1.0)"},"_id":"2042","department":[{"_id":"JoBo"}],"file_date_updated":"2020-07-14T12:45:26Z","ddc":["570"],"date_updated":"2021-01-12T06:54:56Z"},{"oa":1,"quality_controlled":"1","publisher":"BioMed Central","page":"54 - 54","date_created":"2018-12-11T11:57:31Z","date_published":"2013-02-26T00:00:00Z","doi":"10.1186/1471-2148-13-54","year":"2013","has_accepted_license":"1","publication":"BMC Evolutionary Biology","day":"26","publist_id":"4514","author":[{"full_name":"Kupczok, Anne","last_name":"Kupczok","first_name":"Anne","id":"2BB22BC2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","last_name":"Bollback"}],"title":"Probabilistic models for CRISPR spacer content evolution ","citation":{"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.","ista":"Kupczok A, Bollback JP. 2013. Probabilistic models for CRISPR spacer content evolution . BMC Evolutionary Biology. 13(1), 54–54.","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.","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","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","short":"A. Kupczok, J.P. Bollback, BMC Evolutionary Biology 13 (2013) 54–54.","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":1,"intvolume":" 13","month":"02","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."}],"oa_version":"Published Version","issue":"1","volume":13,"publication_status":"published","language":[{"iso":"eng"}],"file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"029c7e0b198c19312b66ecce3cabb22f","file_id":"5268","creator":"system","date_updated":"2020-07-14T12:45:40Z","file_size":518729,"date_created":"2018-12-12T10:17:15Z","file_name":"IST-2015-397-v1+1_1471-2148-13-54.pdf"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","pubrep_id":"397","status":"public","_id":"2412","file_date_updated":"2020-07-14T12:45:40Z","department":[{"_id":"JoBo"}],"date_updated":"2021-01-12T06:57:20Z","ddc":["576"]},{"type":"journal_article","status":"public","pubrep_id":"398","_id":"2410","department":[{"_id":"JoBo"},{"_id":"LifeSc"}],"file_date_updated":"2020-07-14T12:45:40Z","date_updated":"2021-01-12T06:57:19Z","ddc":["576"],"scopus_import":1,"month":"06","intvolume":" 1","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"}],"oa_version":"Published Version","issue":"3","volume":1,"publication_status":"published","file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"5291","checksum":"0751ec74b695567e0cdf02aaf9c26829","creator":"system","file_size":130026,"date_updated":"2020-07-14T12:45:40Z","file_name":"IST-2015-398-v1+1_Genome_Announc.-2013-Redondo-.pdf","date_created":"2018-12-12T10:17:36Z"}],"language":[{"iso":"eng"}],"author":[{"last_name":"Fernandes Redondo","full_name":"Fernandes Redondo, Rodrigo A","orcid":"0000-0002-5837-2793","id":"409D5C96-F248-11E8-B48F-1D18A9856A87","first_name":"Rodrigo A"},{"last_name":"Kupczok","full_name":"Kupczok, Anne","first_name":"Anne","id":"2BB22BC2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Stift, Gertraud","last_name":"Stift","first_name":"Gertraud","id":"2DB195CA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bollback","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"4516","title":"Complete genome sequence of the novel phage MG-B1 infecting bacillus weihenstephanensis","citation":{"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.","short":"R.A. Fernandes Redondo, A. Kupczok, G. Stift, J.P. Bollback, Genome Announcements 1 (2013).","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.","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","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","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","publisher":"American Society for Microbiology","oa":1,"date_published":"2013-06-13T00:00:00Z","doi":"10.1128/genomeA.00216-13","date_created":"2018-12-11T11:57:30Z","has_accepted_license":"1","year":"2013","day":"13","publication":"Genome Announcements"},{"volume":13,"issue":"1","language":[{"iso":"eng"}],"file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"4722","checksum":"52cf48a7c1794676ae8b0029573a84a9","creator":"system","date_updated":"2020-07-14T12:46:36Z","file_size":1150052,"date_created":"2018-12-12T10:08:59Z","file_name":"IST-2018-941-v1+1_2013_Bollback_Evolutionary_interactionspdf.pdf"}],"publication_status":"published","intvolume":" 13","month":"10","scopus_import":1,"oa_version":"Published Version","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"}],"department":[{"_id":"JoBo"}],"file_date_updated":"2020-07-14T12:46:36Z","ddc":["576"],"date_updated":"2021-01-12T08:01:08Z","pubrep_id":"941","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","_id":"500","date_created":"2018-12-11T11:46:49Z","doi":"10.1186/1471-2148-13-222","date_published":"2013-10-09T00:00:00Z","publication":"BMC Evolutionary Biology","day":"09","year":"2013","has_accepted_license":"1","oa":1,"publisher":"BioMed Central","quality_controlled":"1","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","title":"Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza","author":[{"first_name":"Melissa","full_name":"Ward, Melissa","last_name":"Ward"},{"full_name":"Lycett, Samantha","last_name":"Lycett","first_name":"Samantha"},{"last_name":"Avila","full_name":"Avila, Dorita","first_name":"Dorita"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P","last_name":"Bollback","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612"},{"first_name":"Andrew","full_name":"Leigh Brown, Andrew","last_name":"Leigh Brown"}],"publist_id":"7320","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","short":"M. Ward, S. Lycett, D. Avila, J.P. Bollback, A. Leigh Brown, BMC Evolutionary Biology 13 (2013).","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","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","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.","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.","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."},"article_number":"222"},{"doi":"10.1644/12-MAMM-A-169.1","date_published":"2013-12-01T00:00:00Z","date_created":"2018-12-11T11:46:49Z","page":"1331 - 1345","day":"01","publication":"Journal of Mammalogy","has_accepted_license":"1","year":"2013","quality_controlled":"1","publisher":"Oxford University Press","oa":1,"title":"A new species of tapir from the Amazon","author":[{"full_name":"Cozzuol, Mario","last_name":"Cozzuol","first_name":"Mario"},{"full_name":"Clozato, Camila","last_name":"Clozato","first_name":"Camila"},{"first_name":"Elizete","full_name":"Holanda, Elizete","last_name":"Holanda"},{"full_name":"Rodrigues, Flávio","last_name":"Rodrigues","first_name":"Flávio"},{"first_name":"Samuel","last_name":"Nienow","full_name":"Nienow, Samuel"},{"last_name":"De Thoisy","full_name":"De Thoisy, Benoit","first_name":"Benoit"},{"last_name":"Fernandes Redondo","full_name":"Fernandes Redondo, Rodrigo A","orcid":"0000-0002-5837-2793","id":"409D5C96-F248-11E8-B48F-1D18A9856A87","first_name":"Rodrigo A"},{"first_name":"Fabrício","last_name":"Santos","full_name":"Santos, Fabrício"}],"publist_id":"7319","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Cozzuol, Mario, Camila Clozato, Elizete Holanda, Flávio Rodrigues, Samuel Nienow, Benoit De Thoisy, Rodrigo A Fernandes Redondo, and Fabrício Santos. “A New Species of Tapir from the Amazon.” Journal of Mammalogy. Oxford University Press, 2013. https://doi.org/10.1644/12-MAMM-A-169.1.","ista":"Cozzuol M, Clozato C, Holanda E, Rodrigues F, Nienow S, De Thoisy B, Fernandes Redondo RA, Santos F. 2013. A new species of tapir from the Amazon. Journal of Mammalogy. 94(6), 1331–1345.","mla":"Cozzuol, Mario, et al. “A New Species of Tapir from the Amazon.” Journal of Mammalogy, vol. 94, no. 6, Oxford University Press, 2013, pp. 1331–45, doi:10.1644/12-MAMM-A-169.1.","ieee":"M. Cozzuol et al., “A new species of tapir from the Amazon,” Journal of Mammalogy, vol. 94, no. 6. Oxford University Press, pp. 1331–1345, 2013.","short":"M. Cozzuol, C. Clozato, E. Holanda, F. Rodrigues, S. Nienow, B. De Thoisy, R.A. Fernandes Redondo, F. Santos, Journal of Mammalogy 94 (2013) 1331–1345.","apa":"Cozzuol, M., Clozato, C., Holanda, E., Rodrigues, F., Nienow, S., De Thoisy, B., … Santos, F. (2013). A new species of tapir from the Amazon. Journal of Mammalogy. Oxford University Press. https://doi.org/10.1644/12-MAMM-A-169.1","ama":"Cozzuol M, Clozato C, Holanda E, et al. A new species of tapir from the Amazon. Journal of Mammalogy. 2013;94(6):1331-1345. doi:10.1644/12-MAMM-A-169.1"},"volume":94,"issue":"6","file":[{"date_updated":"2020-07-14T12:46:36Z","file_size":1040765,"creator":"system","date_created":"2018-12-12T10:12:59Z","file_name":"IST-2018-940-v1+1_2013_Redondo_A_new.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"8007815078dccac21ecd1cf73a269dc6","file_id":"4980"}],"language":[{"iso":"eng"}],"publication_status":"published","month":"12","intvolume":" 94","scopus_import":1,"oa_version":"Published Version","abstract":[{"text":"All known species of extant tapirs are allopatric: 1 in southeastern Asia and 3 in Central and South America. The fossil record for tapirs, however, is much wider in geographical range, including Europe, Asia, and North and South America, going back to the late Oligocene, making the present distribution a relict of the original one. We here describe a new species of living Tapirus from the Amazon rain forest, the 1st since T. bairdii Gill, 1865, and the 1st new Perissodactyla in more than 100 years, from both morphological and molecular characters. It is shorter in stature than T. terrestris (Linnaeus, 1758) and has distinctive skull morphology, and it is basal to the clade formed by T. terrestris and T. pinchaque (Roulin, 1829). This highlights the unrecognized biodiversity in western Amazonia, where the biota faces increasing threats. Local peoples have long recognized our new species, suggesting a key role for traditional knowledge in understanding the biodiversity of the region.","lang":"eng"}],"department":[{"_id":"JoBo"}],"file_date_updated":"2020-07-14T12:46:36Z","ddc":["570"],"date_updated":"2021-01-12T08:01:09Z","status":"public","pubrep_id":"940","type":"journal_article","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"_id":"501"},{"citation":{"short":"E. Tarazona Santos, M. Machado, W. Magalhães, R. Chen, F. Lyon, L. Burdett, A. Crenshaw, C. Fabbri, L. Pereira, L. Pinto, R.A. Fernandes Redondo, B. Sestanovich, M. Yeager, S. Chanock, Molecular Biology and Evolution 30 (2013) 2157–2167.","ieee":"E. Tarazona Santos et al., “Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications,” Molecular Biology and Evolution, vol. 30, no. 9. Oxford University Press, pp. 2157–2167, 2013.","apa":"Tarazona Santos, E., Machado, M., Magalhães, W., Chen, R., Lyon, F., Burdett, L., … Chanock, S. (2013). Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/mst119","ama":"Tarazona Santos E, Machado M, Magalhães W, et al. Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications. Molecular Biology and Evolution. 2013;30(9):2157-2167. doi:10.1093/molbev/mst119","mla":"Tarazona Santos, Eduardo, et al. “Evolutionary Dynamics of the Human NADPH Oxidase Genes CYBB, CYBA, NCF2, and NCF4: Functional Implications.” Molecular Biology and Evolution, vol. 30, no. 9, Oxford University Press, 2013, pp. 2157–67, doi:10.1093/molbev/mst119.","ista":"Tarazona Santos E, Machado M, Magalhães W, Chen R, Lyon F, Burdett L, Crenshaw A, Fabbri C, Pereira L, Pinto L, Fernandes Redondo RA, Sestanovich B, Yeager M, Chanock S. 2013. Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications. Molecular Biology and Evolution. 30(9), 2157–2167.","chicago":"Tarazona Santos, Eduardo, Moara Machado, Wagner Magalhães, Renee Chen, Fernanda Lyon, Laurie Burdett, Andrew Crenshaw, et al. “Evolutionary Dynamics of the Human NADPH Oxidase Genes CYBB, CYBA, NCF2, and NCF4: Functional Implications.” Molecular Biology and Evolution. Oxford University Press, 2013. https://doi.org/10.1093/molbev/mst119."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Tarazona Santos","full_name":"Tarazona Santos, Eduardo","first_name":"Eduardo"},{"first_name":"Moara","full_name":"Machado, Moara","last_name":"Machado"},{"full_name":"Magalhães, Wagner","last_name":"Magalhães","first_name":"Wagner"},{"first_name":"Renee","full_name":"Chen, Renee","last_name":"Chen"},{"last_name":"Lyon","full_name":"Lyon, Fernanda","first_name":"Fernanda"},{"first_name":"Laurie","full_name":"Burdett, Laurie","last_name":"Burdett"},{"first_name":"Andrew","last_name":"Crenshaw","full_name":"Crenshaw, Andrew"},{"first_name":"Cristina","last_name":"Fabbri","full_name":"Fabbri, Cristina"},{"first_name":"Latife","last_name":"Pereira","full_name":"Pereira, Latife"},{"last_name":"Pinto","full_name":"Pinto, Laelia","first_name":"Laelia"},{"id":"409D5C96-F248-11E8-B48F-1D18A9856A87","first_name":"Rodrigo A","full_name":"Fernandes Redondo, Rodrigo A","orcid":"0000-0002-5837-2793","last_name":"Fernandes Redondo"},{"full_name":"Sestanovich, Ben","last_name":"Sestanovich","first_name":"Ben"},{"full_name":"Yeager, Meredith","last_name":"Yeager","first_name":"Meredith"},{"full_name":"Chanock, Stephen","last_name":"Chanock","first_name":"Stephen"}],"publist_id":"7310","external_id":{"pmid":["23821607"]},"title":"Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications","quality_controlled":"1","publisher":"Oxford University Press","oa":1,"year":"2013","day":"01","publication":"Molecular Biology and Evolution","page":"2157 - 2167","doi":"10.1093/molbev/mst119","date_published":"2013-09-01T00:00:00Z","date_created":"2018-12-11T11:46:52Z","_id":"508","type":"journal_article","status":"public","date_updated":"2021-01-12T08:01:12Z","department":[{"_id":"JoBo"}],"abstract":[{"text":"The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.","lang":"eng"}],"oa_version":"Submitted Version","pmid":1,"scopus_import":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748357/","open_access":"1"}],"month":"09","intvolume":" 30","publication_status":"published","language":[{"iso":"eng"}],"issue":"9","volume":30},{"page":"1319 - 1334","date_published":"2012-05-01T00:00:00Z","doi":"10.1093/molbev/msr285","date_created":"2018-12-11T11:57:30Z","has_accepted_license":"1","year":"2012","day":"01","publication":"Molecular Biology and Evolution","quality_controlled":"1","publisher":"Oxford University Press","oa":1,"publist_id":"4515","author":[{"last_name":"Ebersberger","full_name":"Ebersberger, Ingo","first_name":"Ingo"},{"first_name":"Ricardo","last_name":"De Matos Simoes","full_name":"De Matos Simoes, Ricardo"},{"last_name":"Kupczok","full_name":"Kupczok, Anne","first_name":"Anne","id":"2BB22BC2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gube, Matthias","last_name":"Gube","first_name":"Matthias"},{"full_name":"Kothe, Erika","last_name":"Kothe","first_name":"Erika"},{"last_name":"Voigt","full_name":"Voigt, Kerstin","first_name":"Kerstin"},{"full_name":"Von Haeseler, Arndt","last_name":"Von Haeseler","first_name":"Arndt"}],"title":"A consistent phylogenetic backbone for the fungi","citation":{"mla":"Ebersberger, Ingo, et al. “A Consistent Phylogenetic Backbone for the Fungi.” Molecular Biology and Evolution, vol. 29, no. 5, Oxford University Press, 2012, pp. 1319–34, doi:10.1093/molbev/msr285.","apa":"Ebersberger, I., De Matos Simoes, R., Kupczok, A., Gube, M., Kothe, E., Voigt, K., & Von Haeseler, A. (2012). A consistent phylogenetic backbone for the fungi. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msr285","ama":"Ebersberger I, De Matos Simoes R, Kupczok A, et al. A consistent phylogenetic backbone for the fungi. Molecular Biology and Evolution. 2012;29(5):1319-1334. doi:10.1093/molbev/msr285","short":"I. Ebersberger, R. De Matos Simoes, A. Kupczok, M. Gube, E. Kothe, K. Voigt, A. Von Haeseler, Molecular Biology and Evolution 29 (2012) 1319–1334.","ieee":"I. Ebersberger et al., “A consistent phylogenetic backbone for the fungi,” Molecular Biology and Evolution, vol. 29, no. 5. Oxford University Press, pp. 1319–1334, 2012.","chicago":"Ebersberger, Ingo, Ricardo De Matos Simoes, Anne Kupczok, Matthias Gube, Erika Kothe, Kerstin Voigt, and Arndt Von Haeseler. “A Consistent Phylogenetic Backbone for the Fungi.” Molecular Biology and Evolution. Oxford University Press, 2012. https://doi.org/10.1093/molbev/msr285.","ista":"Ebersberger I, De Matos Simoes R, Kupczok A, Gube M, Kothe E, Voigt K, Von Haeseler A. 2012. A consistent phylogenetic backbone for the fungi. Molecular Biology and Evolution. 29(5), 1319–1334."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","issue":"5","volume":29,"publication_status":"published","file":[{"file_size":754922,"date_updated":"2020-07-14T12:45:40Z","creator":"system","file_name":"IST-2015-384-v1+1_Mol_Biol_Evol-2012-Ebersberger-1319-34.pdf","date_created":"2018-12-12T10:13:30Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_id":"5013","checksum":"d565dcac27d1736c0c378ea6fcf22d69"}],"language":[{"iso":"eng"}],"scopus_import":1,"month":"05","intvolume":" 29","abstract":[{"lang":"eng","text":"The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data-a common practice in phylogenomic analyses-introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses."}],"oa_version":"Published Version","department":[{"_id":"JoBo"}],"file_date_updated":"2020-07-14T12:45:40Z","date_updated":"2021-01-12T06:57:19Z","ddc":["570","576"],"type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"status":"public","pubrep_id":"384","_id":"2411"}]