{"publisher":"Elsevier","quality_controlled":"1","citation":{"apa":"Mascolo, E., Körei, R. E., Herrera-Álvarez, S., Guet, C. C., Crocker, J., &#38; Tkačik, G. (2026). Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps. <i>Current Opinion in Genetics &#38; Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.gde.2026.102483\">https://doi.org/10.1016/j.gde.2026.102483</a>","ama":"Mascolo E, Körei RE, Herrera-Álvarez S, Guet CC, Crocker J, Tkačik G. Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps. <i>Current Opinion in Genetics &#38; Development</i>. 2026;99. doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102483\">10.1016/j.gde.2026.102483</a>","chicago":"Mascolo, Elia, Reka E Körei, Santiago Herrera-Álvarez, Calin C Guet, Justin Crocker, and Gašper Tkačik. “Long-Term Evolution of Regulatory DNA Sequences. Part 1: Simulations on Global, Biophysically-Realistic Genotype–Phenotype Maps.” <i>Current Opinion in Genetics &#38; Development</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.gde.2026.102483\">https://doi.org/10.1016/j.gde.2026.102483</a>.","ista":"Mascolo E, Körei RE, Herrera-Álvarez S, Guet CC, Crocker J, Tkačik G. 2026. Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps. Current Opinion in Genetics &#38; Development. 99, 102483.","ieee":"E. Mascolo, R. E. Körei, S. Herrera-Álvarez, C. C. Guet, J. Crocker, and G. Tkačik, “Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps,” <i>Current Opinion in Genetics &#38; Development</i>, vol. 99. Elsevier, 2026.","short":"E. Mascolo, R.E. Körei, S. Herrera-Álvarez, C.C. Guet, J. Crocker, G. Tkačik, Current Opinion in Genetics &#38; Development 99 (2026).","mla":"Mascolo, Elia, et al. “Long-Term Evolution of Regulatory DNA Sequences. Part 1: Simulations on Global, Biophysically-Realistic Genotype–Phenotype Maps.” <i>Current Opinion in Genetics &#38; Development</i>, vol. 99, 102483, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102483\">10.1016/j.gde.2026.102483</a>."},"ddc":["570"],"day":"09","oa_version":"Published Version","article_processing_charge":"Yes (via OA deal)","_id":"21983","scopus_import":"1","article_type":"original","department":[{"_id":"GradSch"},{"_id":"CaGu"},{"_id":"GaTk"}],"intvolume":"        99","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.gde.2026.102483"}],"date_updated":"2026-06-16T12:37:02Z","abstract":[{"text":"Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an individual TF binds arbitrary DNA sequences and how individual binding events on the CRE combine to affect gene expression. These insights can be synthesized into a global, biophysically realistic, and quantitative genotype–phenotype map for gene regulation, a ‘holy grail’ for the application of evolutionary theory. A global map provides a rare opportunity to simulate the long-term evolution of regulatory sequences and pose several fundamental questions: How long does it take to evolve CREs de novo? How many non-trivial regulatory functions exist in sequence space? How connected are they? For which regulatory architecture is CRE evolution most rapid and evolvable? In this article, the first of a two-part series, we briefly review the pertinent modeling and simulation efforts for a unique system that enables close, quantitative, and mechanistic links between biophysics, as well as systems, synthetic, and evolutionary biology.","lang":"eng"}],"title":"Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps","author":[{"last_name":"Mascolo","first_name":"Elia","orcid":"0000-0003-2977-7844","full_name":"Mascolo, Elia","id":"776a6ed0-a053-11f0-8635-80b95e0e0d53"},{"full_name":"Körei, Reka E","id":"50FDE43E-AA30-11E9-A72B-8A12E6697425","first_name":"Reka E","last_name":"Körei"},{"last_name":"Herrera-Álvarez","first_name":"Santiago","full_name":"Herrera-Álvarez, Santiago"},{"orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Crocker, Justin","last_name":"Crocker","first_name":"Justin"},{"full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"date_created":"2026-06-10T07:37:12Z","external_id":{"arxiv":["2601.19681"]},"date_published":"2026-05-09T00:00:00Z","OA_type":"hybrid","corr_author":"1","article_number":"102483","publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"Current Opinion in Genetics & Development","publication_identifier":{"eissn":["1879-0380"],"issn":["0959-437X"]},"status":"public","OA_place":"publisher","volume":99,"type":"journal_article","acknowledgement":"We thank Nick Barton and Noa Ottilie Borst for essential contributions to this manuscript.\r\nE.M. acknowledges support from the APART-USA fellowship, jointly funded by the Austrian Academy of Sciences (ÖAW) and the Institute of Science and Technology Austria (ISTA).\r\nThis study was supported by the European Molecular Biology Laboratory (J.C.); the European Molecular Biology Laboratory Interdisciplinary Postdoc Programme (EIPOD) under the Marie Skłodowska-Curie Actions cofund (S.H.A.).","arxiv":1,"month":"05","has_accepted_license":"1","PlanS_conform":"1","doi":"10.1016/j.gde.2026.102483","oa":1,"year":"2026","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"language":[{"iso":"eng"}]}