--- _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' ...