{"acknowledgement":"TFs regulate gene expression by binding to specific sequences in the promoter regions of their target genes. Promoters often contain multiple copies of the same TF binding sites. How does this multiplicity evolve? One possibility is that individuals with multiple, redundant binding sites have higher fitness. However, nonadaptive processes are also likely to be important. Here, we develop a mathematical model of the evolution of TF binding sites to help us disentangle how different evolutionary mechanisms contribute to the evolution of binding site redundancy and multiplicity. We show that recombination is expected to promote the evolution of multiple binding sites. This prediction is corroborated by genome-wide data from yeast. Another important factor in the evolution of multiplicity predicted in our analysis is TF promiscuity, that is, the ability of a TF to bind to multiple sequences. In addition, our analysis indicated that direct selection can have large effects on the evolution of redundancy and multiplicity. Data from yeast identified selection for changes in expression level as a candidate mechanism for the evolution of multiple binding sites. We conclude that, although selection may play a major role in the evolution of multiplicity in regulatory regions, nonadaptive forces can also lead to high levels of multiplicity.","tmp":{"short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png"},"doi":"10.1371/journal.pcbi.1000848","citation":{"ieee":"T. Paixao and R. Azevedo, “Redundancy and the Evolution of Cis Regulatory Element Multiplicity,” <i>PLoS Computational Biology</i>, vol. 6, no. 7. Public Library of Science, 2011.","ama":"Paixao T, Azevedo R. Redundancy and the Evolution of Cis Regulatory Element Multiplicity. <i>PLoS Computational Biology</i>. 2011;6(7). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1000848\">10.1371/journal.pcbi.1000848</a>","chicago":"Paixao, Tiago, and Ricardo Azevedo. “Redundancy and the Evolution of Cis Regulatory Element Multiplicity.” <i>PLoS Computational Biology</i>. Public Library of Science, 2011. <a href=\"https://doi.org/10.1371/journal.pcbi.1000848\">https://doi.org/10.1371/journal.pcbi.1000848</a>.","mla":"Paixao, Tiago, and Ricardo Azevedo. “Redundancy and the Evolution of Cis Regulatory Element Multiplicity.” <i>PLoS Computational Biology</i>, vol. 6, no. 7, Public Library of Science, 2011, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1000848\">10.1371/journal.pcbi.1000848</a>.","ista":"Paixao T, Azevedo R. 2011. Redundancy and the Evolution of Cis Regulatory Element Multiplicity. PLoS Computational Biology. 6(7).","apa":"Paixao, T., &#38; Azevedo, R. (2011). Redundancy and the Evolution of Cis Regulatory Element Multiplicity. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1000848\">https://doi.org/10.1371/journal.pcbi.1000848</a>","short":"T. Paixao, R. Azevedo, PLoS Computational Biology 6 (2011)."},"publication_status":"published","issue":"7","extern":1,"publisher":"Public Library of Science","publist_id":"3861","intvolume":"         6","title":"Redundancy and the Evolution of Cis Regulatory Element Multiplicity","_id":"2897","quality_controlled":0,"volume":6,"month":"01","date_updated":"2021-01-12T07:00:33Z","date_created":"2018-12-11T12:00:13Z","publication":"PLoS Computational Biology","status":"public","type":"journal_article","day":"01","year":"2011","date_published":"2011-01-01T00:00:00Z","author":[{"orcid":"0000-0003-2361-3953","full_name":"Tiago Paixao","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago"},{"first_name":"Ricardo","last_name":"Azevedo","full_name":"Azevedo, Ricardo B"}]}