[{"related_material":{"record":[{"id":"1666","status":"public","relation":"part_of_dissertation"},{"status":"public","id":"5554","relation":"research_data"}]},"language":[{"iso":"eng"}],"file":[{"date_created":"2019-08-13T08:53:52Z","file_name":"Tugrul_thesis_w_signature_page.pdf","creator":"dernst","date_updated":"2019-08-13T08:53:52Z","file_size":3695257,"checksum":"66cb61a59943e4fb7447c6a86be5ef51","file_id":"6810","access_level":"closed","relation":"main_file","content_type":"application/pdf"},{"file_name":"2016_Tugrul_Thesis.pdf","date_created":"2021-02-22T11:45:20Z","file_size":3880811,"date_updated":"2021-02-22T11:45:20Z","creator":"dernst","success":1,"file_id":"9182","checksum":"293e388d70563760f6b24c3e66283dda","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"month":"07","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Evolution of gene regulation is important for phenotypic evolution and diversity. Sequence-specific binding of regulatory proteins is one of the key regulatory mechanisms determining gene expression. Although there has been intense interest in evolution of regulatory binding sites in the last decades, a theoretical understanding is far from being complete. In this thesis, I aim at a better understanding of the evolution of transcriptional regulatory binding sequences by using biophysical and population genetic models.\r\nIn the first part of the thesis, I discuss how to formulate the evolutionary dynamics of binding se- quences in a single isolated binding site and in promoter/enhancer regions. I develop a theoretical framework bridging between a thermodynamical model for transcription and a mutation-selection-drift model for monomorphic populations. I mainly address the typical evolutionary rates, and how they de- pend on biophysical parameters (e.g. binding length and specificity) and population genetic parameters (e.g. population size and selection strength).\r\nIn the second part of the thesis, I analyse empirical data for a better evolutionary and biophysical understanding of sequence-specific binding of bacterial RNA polymerase. First, I infer selection on regulatory and non-regulatory binding sites of RNA polymerase in the E. coli K12 genome. Second, I infer the chemical potential of RNA polymerase, an important but unknown physical parameter defining the threshold energy for strong binding. Furthermore, I try to understand the relation between the lac promoter sequence diversity and the LacZ activity variation among 20 bacterial isolates by constructing a simple but biophysically motivated gene expression model. Lastly, I lay out a statistical framework to predict adaptive point mutations in de novo promoter evolution in a selection experiment."}],"department":[{"_id":"NiBa"}],"file_date_updated":"2021-02-22T11:45:20Z","ddc":["576"],"date_updated":"2024-02-21T13:50:34Z","supervisor":[{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H","last_name":"Barton","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240"}],"status":"public","type":"dissertation","_id":"1131","date_created":"2018-12-11T11:50:19Z","date_published":"2016-07-01T00:00:00Z","page":"89","day":"01","year":"2016","has_accepted_license":"1","oa":1,"publisher":"Institute of Science and Technology Austria","acknowledgement":"This PhD thesis may not have been completed without the help and care I received from some peo- ple during my PhD life. I am especially grateful to Tiago Paixao, Gasper Tkacik, Nick Barton, not only for their scientific advices but also for their patience and support. I thank Calin Guet and Jonathan Bollback for allowing me to “play around” in their labs and get some experience on experimental evolution. I thank Magdalena Steinrueck and Fabienne Jesse for collaborating and sharing their experimental data with me. I thank Johannes Jaeger for reviewing my thesis. I thank all members of Barton group (aka bartonians) for their feedback, and all workers of IST Austria for making the best working conditions. Lastly, I thank two special women, Nejla Sag ̆lam and Setenay Dog ̆an, for their continuous support and encouragement. I truly had a great chance of having right people around me.","title":"Evolution of transcriptional regulatory sequences","article_processing_charge":"No","publist_id":"6229","author":[{"id":"37C323C6-F248-11E8-B48F-1D18A9856A87","first_name":"Murat","last_name":"Tugrul","orcid":"0000-0002-8523-0758","full_name":"Tugrul, Murat"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Tugrul, Murat. Evolution of Transcriptional Regulatory Sequences. Institute of Science and Technology Austria, 2016.","apa":"Tugrul, M. (2016). Evolution of transcriptional regulatory sequences. Institute of Science and Technology Austria.","ama":"Tugrul M. Evolution of transcriptional regulatory sequences. 2016.","ieee":"M. Tugrul, “Evolution of transcriptional regulatory sequences,” Institute of Science and Technology Austria, 2016.","short":"M. Tugrul, Evolution of Transcriptional Regulatory Sequences, Institute of Science and Technology Austria, 2016.","chicago":"Tugrul, Murat. “Evolution of Transcriptional Regulatory Sequences.” Institute of Science and Technology Austria, 2016.","ista":"Tugrul M. 2016. Evolution of transcriptional regulatory sequences. Institute of Science and Technology Austria."}},{"author":[{"orcid":"0000-0002-8523-0758","full_name":"Tugrul, Murat","last_name":"Tugrul","id":"37C323C6-F248-11E8-B48F-1D18A9856A87","first_name":"Murat"}],"article_processing_charge":"No","file_date_updated":"2020-07-14T12:47:01Z","title":"Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase","department":[{"_id":"NiBa"},{"_id":"JoBo"}],"citation":{"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.","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.","short":"M. Tugrul, (2016).","ieee":"M. Tugrul, “Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase.” Institute of Science and Technology Austria, 2016.","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","ama":"Tugrul M. Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase. 2016. doi:10.15479/AT:ISTA:43"},"date_updated":"2024-02-21T13:50:34Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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"],"_id":"5554","date_published":"2016-05-12T00:00:00Z","related_material":{"record":[{"status":"public","id":"1131","relation":"used_in_publication"}]},"doi":"10.15479/AT:ISTA:43","date_created":"2018-12-12T12:31:30Z","contributor":[{"id":"2C023F40-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","first_name":"Magdalena","last_name":"Steinrück"},{"last_name":"Jesse","id":"4C8C26A4-F248-11E8-B48F-1D18A9856A87","contributor_type":"researcher","first_name":"Fabienne"}],"has_accepted_license":"1","year":"2016","datarep_id":"43","day":"12","file":[{"relation":"main_file","access_level":"open_access","content_type":"application/zip","file_id":"5626","checksum":"1fc0a10bb7ce110fcb5e1fbe3cf0c4e2","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"}],"publisher":"Institute of Science and Technology Austria","oa":1,"month":"05","abstract":[{"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.","lang":"eng"}],"oa_version":"Published Version"},{"article_number":"022803","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Keller-Schmidt S, Tugrul M, Eguíluz V, Hernandez Garcia E, Klemm K. 2015. Anomalous scaling in an age-dependent branching model. Physical Review E Statistical Nonlinear and Soft Matter Physics. 91(2), 022803.","chicago":"Keller-Schmidt, Stephanie, Murat Tugrul, Víctor Eguíluz, Emilio Hernandez Garcia, and Konstantin Klemm. “Anomalous Scaling in an Age-Dependent Branching Model.” Physical Review E Statistical Nonlinear and Soft Matter Physics. American Institute of Physics, 2015. https://doi.org/10.1103/PhysRevE.91.022803.","short":"S. Keller-Schmidt, M. Tugrul, V. Eguíluz, E. Hernandez Garcia, K. Klemm, Physical Review E Statistical Nonlinear and Soft Matter Physics 91 (2015).","ieee":"S. Keller-Schmidt, M. Tugrul, V. Eguíluz, E. Hernandez Garcia, and K. Klemm, “Anomalous scaling in an age-dependent branching model,” Physical Review E Statistical Nonlinear and Soft Matter Physics, vol. 91, no. 2. American Institute of Physics, 2015.","ama":"Keller-Schmidt S, Tugrul M, Eguíluz V, Hernandez Garcia E, Klemm K. Anomalous scaling in an age-dependent branching model. Physical Review E Statistical Nonlinear and Soft Matter Physics. 2015;91(2). doi:10.1103/PhysRevE.91.022803","apa":"Keller-Schmidt, S., Tugrul, M., Eguíluz, V., Hernandez Garcia, E., & Klemm, K. (2015). Anomalous scaling in an age-dependent branching model. Physical Review E Statistical Nonlinear and Soft Matter Physics. American Institute of Physics. https://doi.org/10.1103/PhysRevE.91.022803","mla":"Keller-Schmidt, Stephanie, et al. “Anomalous Scaling in an Age-Dependent Branching Model.” Physical Review E Statistical Nonlinear and Soft Matter Physics, vol. 91, no. 2, 022803, American Institute of Physics, 2015, doi:10.1103/PhysRevE.91.022803."},"title":"Anomalous scaling in an age-dependent branching model","author":[{"first_name":"Stephanie","full_name":"Keller-Schmidt, Stephanie","last_name":"Keller-Schmidt"},{"first_name":"Murat","id":"37C323C6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8523-0758","full_name":"Tugrul, Murat","last_name":"Tugrul"},{"full_name":"Eguíluz, Víctor","last_name":"Eguíluz","first_name":"Víctor"},{"first_name":"Emilio","full_name":"Hernandez Garcia, Emilio","last_name":"Hernandez Garcia"},{"first_name":"Konstantin","full_name":"Klemm, Konstantin","last_name":"Klemm"}],"publist_id":"5213","external_id":{"arxiv":["1012.3298"]},"article_processing_charge":"No","quality_controlled":"1","publisher":"American Institute of Physics","oa":1,"day":"02","publication":"Physical Review E Statistical Nonlinear and Soft Matter Physics","year":"2015","date_published":"2015-02-02T00:00:00Z","doi":"10.1103/PhysRevE.91.022803","date_created":"2018-12-11T11:54:31Z","_id":"1883","status":"public","article_type":"original","type":"journal_article","date_updated":"2021-01-12T06:53:49Z","department":[{"_id":"NiBa"}],"oa_version":"Preprint","abstract":[{"lang":"eng","text":"We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ-α. Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)2. This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.\r\n"}],"month":"02","intvolume":" 91","scopus_import":1,"main_file_link":[{"url":"https://arxiv.org/abs/1012.3298","open_access":"1"}],"language":[{"iso":"eng"}],"publication_status":"published","volume":91,"issue":"2"},{"oa_version":"Published Version","publisher":"Public Library of Science","month":"11","year":"2015","day":"06","date_published":"2015-11-06T00:00:00Z","doi":"10.1371/journal.pgen.1005639.s001","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"1666"}]},"date_created":"2021-07-23T12:00:37Z","_id":"9712","type":"research_data_reference","status":"public","date_updated":"2023-02-23T10:09:08Z","citation":{"mla":"Tugrul, Murat, et al. Other Fitness Models for Comparison & for Interacting TFBSs. Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639.s001.","short":"M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, (2015).","ieee":"M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Other fitness models for comparison & for interacting TFBSs.” Public Library of Science, 2015.","apa":"Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Other fitness models for comparison & for interacting TFBSs. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005639.s001","ama":"Tugrul M, Paixao T, Barton NH, Tkačik G. Other fitness models for comparison & for interacting TFBSs. 2015. doi:10.1371/journal.pgen.1005639.s001","chicago":"Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Other Fitness Models for Comparison & for Interacting TFBSs.” Public Library of Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.s001.","ista":"Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Other fitness models for comparison & for interacting TFBSs, Public Library of Science, 10.1371/journal.pgen.1005639.s001."},"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","author":[{"last_name":"Tugrul","full_name":"Tugrul, Murat","orcid":"0000-0002-8523-0758","id":"37C323C6-F248-11E8-B48F-1D18A9856A87","first_name":"Murat"},{"first_name":"Tiago","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","last_name":"Paixao","orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago"},{"full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H"},{"last_name":"Tkačik","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","department":[{"_id":"NiBa"},{"_id":"CaGu"},{"_id":"GaTk"}],"title":"Other fitness models for comparison & for interacting TFBSs"},{"date_created":"2018-12-11T11:53:21Z","date_published":"2015-11-06T00:00:00Z","doi":"10.1371/journal.pgen.1005639","publication":"PLoS Genetics","day":"06","year":"2015","has_accepted_license":"1","oa":1,"quality_controlled":"1","publisher":"Public Library of Science","title":"Dynamics of transcription factor binding site evolution","author":[{"last_name":"Tugrul","full_name":"Tugrul, Murat","orcid":"0000-0002-8523-0758","first_name":"Murat","id":"37C323C6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Paixao","full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago"},{"first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240"},{"first_name":"Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkacik","orcid":"0000-0002-6699-1455","full_name":"Tkacik, Gasper"}],"publist_id":"5483","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Dynamics of transcription factor binding site evolution. PLoS Genetics. 11(11).","chicago":"Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Dynamics of Transcription Factor Binding Site Evolution.” PLoS Genetics. Public Library of Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.","ama":"Tugrul M, Paixao T, Barton NH, Tkačik G. Dynamics of transcription factor binding site evolution. PLoS Genetics. 2015;11(11). doi:10.1371/journal.pgen.1005639","apa":"Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Dynamics of transcription factor binding site evolution. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005639","ieee":"M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Dynamics of transcription factor binding site evolution,” PLoS Genetics, vol. 11, no. 11. Public Library of Science, 2015.","short":"M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, PLoS Genetics 11 (2015).","mla":"Tugrul, Murat, et al. “Dynamics of Transcription Factor Binding Site Evolution.” PLoS Genetics, vol. 11, no. 11, Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639."},"project":[{"_id":"25B07788-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Limits to selection in biology and in evolutionary computation","grant_number":"250152"}],"ec_funded":1,"issue":"11","volume":11,"related_material":{"record":[{"id":"9712","status":"public","relation":"research_data"},{"id":"1131","status":"public","relation":"dissertation_contains"}]},"language":[{"iso":"eng"}],"file":[{"date_created":"2018-12-12T10:07:58Z","file_name":"IST-2016-463-v1+1_journal.pgen.1005639.pdf","creator":"system","date_updated":"2020-07-14T12:45:10Z","file_size":2580778,"checksum":"a4e72fca5ccf40ddacf4d08c8e46b554","file_id":"4657","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"publication_status":"published","intvolume":" 11","month":"11","scopus_import":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of “pre-sites” or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genomics."}],"file_date_updated":"2020-07-14T12:45:10Z","department":[{"_id":"NiBa"},{"_id":"CaGu"},{"_id":"GaTk"}],"ddc":["576"],"date_updated":"2023-09-07T11:53:49Z","pubrep_id":"463","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":"1666"}]