--- _id: '1131' 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." 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. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Murat full_name: Tugrul, Murat id: 37C323C6-F248-11E8-B48F-1D18A9856A87 last_name: Tugrul orcid: 0000-0002-8523-0758 citation: ama: Tugrul M. Evolution of transcriptional regulatory sequences. 2016. apa: Tugrul, M. (2016). Evolution of transcriptional regulatory sequences. Institute of Science and Technology Austria. chicago: Tugrul, Murat. “Evolution of Transcriptional Regulatory Sequences.” Institute of Science and Technology Austria, 2016. ieee: M. Tugrul, “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. mla: Tugrul, Murat. 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. date_created: 2018-12-11T11:50:19Z date_published: 2016-07-01T00:00:00Z date_updated: 2024-02-21T13:50:34Z day: '01' ddc: - '576' degree_awarded: PhD department: - _id: NiBa file: - access_level: closed checksum: 66cb61a59943e4fb7447c6a86be5ef51 content_type: application/pdf creator: dernst date_created: 2019-08-13T08:53:52Z date_updated: 2019-08-13T08:53:52Z file_id: '6810' file_name: Tugrul_thesis_w_signature_page.pdf file_size: 3695257 relation: main_file - access_level: open_access checksum: 293e388d70563760f6b24c3e66283dda content_type: application/pdf creator: dernst date_created: 2021-02-22T11:45:20Z date_updated: 2021-02-22T11:45:20Z file_id: '9182' file_name: 2016_Tugrul_Thesis.pdf file_size: 3880811 relation: main_file success: 1 file_date_updated: 2021-02-22T11:45:20Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '89' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria publist_id: '6229' related_material: record: - id: '1666' relation: part_of_dissertation status: public - id: '5554' relation: research_data status: public status: public supervisor: - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 title: Evolution of transcriptional regulatory sequences type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2016' ... --- _id: '5554' 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." article_processing_charge: No author: - first_name: Murat full_name: Tugrul, Murat id: 37C323C6-F248-11E8-B48F-1D18A9856A87 last_name: Tugrul orcid: 0000-0002-8523-0758 citation: 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 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. ieee: M. Tugrul, “Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase.” Institute of Science and Technology Austria, 2016. 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). contributor: - contributor_type: researcher first_name: Magdalena id: 2C023F40-F248-11E8-B48F-1D18A9856A87 last_name: Steinrück - contributor_type: researcher first_name: Fabienne id: 4C8C26A4-F248-11E8-B48F-1D18A9856A87 last_name: Jesse datarep_id: '43' date_created: 2018-12-12T12:31:30Z date_published: 2016-05-12T00:00:00Z date_updated: 2024-02-21T13:50:34Z day: '12' department: - _id: NiBa - _id: JoBo doi: 10.15479/AT:ISTA:43 file: - access_level: open_access checksum: 1fc0a10bb7ce110fcb5e1fbe3cf0c4e2 content_type: application/zip creator: system date_created: 2018-12-12T13:03:08Z date_updated: 2020-07-14T12:47:01Z file_id: '5626' file_name: IST-2016-43-v1+1_DATA_MTugrul_PhDThesis_Chapter3.zip file_size: 1123495 relation: main_file file_date_updated: 2020-07-14T12:47:01Z has_accepted_license: '1' keyword: - RNAP binding - de novo promoter evolution - lac promoter license: https://creativecommons.org/publicdomain/zero/1.0/ month: '05' oa: 1 oa_version: Published Version publisher: Institute of Science and Technology Austria related_material: record: - id: '1131' relation: used_in_publication status: public status: public title: Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase 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) type: research_data user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2016' ... --- _id: '1883' 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" article_number: '022803' article_processing_charge: No article_type: original author: - first_name: Stephanie full_name: Keller-Schmidt, Stephanie last_name: Keller-Schmidt - first_name: Murat full_name: Tugrul, Murat id: 37C323C6-F248-11E8-B48F-1D18A9856A87 last_name: Tugrul orcid: 0000-0002-8523-0758 - first_name: Víctor full_name: Eguíluz, Víctor last_name: Eguíluz - first_name: Emilio full_name: Hernandez Garcia, Emilio last_name: Hernandez Garcia - first_name: Konstantin full_name: Klemm, Konstantin last_name: Klemm citation: 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 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. 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. 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. 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. short: S. Keller-Schmidt, M. Tugrul, V. Eguíluz, E. Hernandez Garcia, K. Klemm, Physical Review E Statistical Nonlinear and Soft Matter Physics 91 (2015). date_created: 2018-12-11T11:54:31Z date_published: 2015-02-02T00:00:00Z date_updated: 2021-01-12T06:53:49Z day: '02' department: - _id: NiBa doi: 10.1103/PhysRevE.91.022803 external_id: arxiv: - '1012.3298' intvolume: ' 91' issue: '2' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1012.3298 month: '02' oa: 1 oa_version: Preprint publication: Physical Review E Statistical Nonlinear and Soft Matter Physics publication_status: published publisher: American Institute of Physics publist_id: '5213' quality_controlled: '1' scopus_import: 1 status: public title: Anomalous scaling in an age-dependent branching model type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 91 year: '2015' ... --- _id: '9712' article_processing_charge: No author: - first_name: Murat full_name: Tugrul, Murat id: 37C323C6-F248-11E8-B48F-1D18A9856A87 last_name: Tugrul orcid: 0000-0002-8523-0758 - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 citation: 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 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 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. ieee: M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Other fitness models for comparison & for interacting TFBSs.” Public Library of Science, 2015. 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. 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). date_created: 2021-07-23T12:00:37Z date_published: 2015-11-06T00:00:00Z date_updated: 2023-02-23T10:09:08Z day: '06' department: - _id: NiBa - _id: CaGu - _id: GaTk doi: 10.1371/journal.pgen.1005639.s001 month: '11' oa_version: Published Version publisher: Public Library of Science related_material: record: - id: '1666' relation: used_in_publication status: public status: public title: Other fitness models for comparison & for interacting TFBSs type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2015' ... --- _id: '1666' 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. author: - first_name: Murat full_name: Tugrul, Murat id: 37C323C6-F248-11E8-B48F-1D18A9856A87 last_name: Tugrul orcid: 0000-0002-8523-0758 - first_name: Tiago full_name: Paixao, Tiago id: 2C5658E6-F248-11E8-B48F-1D18A9856A87 last_name: Paixao orcid: 0000-0003-2361-3953 - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Gasper full_name: Tkacik, Gasper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkacik orcid: 0000-0002-6699-1455 citation: 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 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. 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. ista: Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Dynamics of transcription factor binding site evolution. PLoS Genetics. 11(11). 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. short: M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, PLoS Genetics 11 (2015). date_created: 2018-12-11T11:53:21Z date_published: 2015-11-06T00:00:00Z date_updated: 2023-09-07T11:53:49Z day: '06' ddc: - '576' department: - _id: NiBa - _id: CaGu - _id: GaTk doi: 10.1371/journal.pgen.1005639 ec_funded: 1 file: - access_level: open_access checksum: a4e72fca5ccf40ddacf4d08c8e46b554 content_type: application/pdf creator: system date_created: 2018-12-12T10:07:58Z date_updated: 2020-07-14T12:45:10Z file_id: '4657' file_name: IST-2016-463-v1+1_journal.pgen.1005639.pdf file_size: 2580778 relation: main_file file_date_updated: 2020-07-14T12:45:10Z has_accepted_license: '1' intvolume: ' 11' issue: '11' language: - iso: eng month: '11' oa: 1 oa_version: Published Version project: - _id: 25B07788-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '250152' name: Limits to selection in biology and in evolutionary computation publication: PLoS Genetics publication_status: published publisher: Public Library of Science publist_id: '5483' pubrep_id: '463' quality_controlled: '1' related_material: record: - id: '9712' relation: research_data status: public - id: '1131' relation: dissertation_contains status: public scopus_import: 1 status: public title: Dynamics of transcription factor binding site evolution tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 11 year: '2015' ...