{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T01:39:30Z","timestamp":1775612370879,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012028","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000}}],"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Intrinsically disordered regions (IDRs) are segments of proteins without stable three-dimensional structures. As this flexibility allows them to interact with diverse binding partners, IDRs play key roles in cell signaling and gene expression. Despite the prevalence and importance of IDRs in eukaryotic proteomes and various biological processes, associating them with specific molecular functions remains a significant challenge due to their high rates of sequence evolution. However, by comparing the observed values of various IDR-associated properties against those generated under a simulated model of evolution, a recent study found most IDRs across the entire yeast proteome contain conserved features. Furthermore, it showed clusters of IDRs with common \u201cevolutionary signatures,\u201d <jats:italic>i<\/jats:italic>.<jats:italic>e<\/jats:italic>. patterns of conserved features, were associated with specific biological functions. To determine if similar patterns of conservation are found in the IDRs of other systems, in this work we applied a series of phylogenetic models to over 7,500 orthologous IDRs identified in the <jats:italic>Drosophila<\/jats:italic> genome to dissect the forces driving their evolution. By comparing models of constrained and unconstrained continuous trait evolution using the Brownian motion and Ornstein-Uhlenbeck models, respectively, we identified signals of widespread constraint, indicating conservation of distributed features is mechanism of IDR evolution common to multiple biological systems. In contrast to the previous study in yeast, however, we observed limited evidence of IDR clusters with specific biological functions, which suggests a more complex relationship between evolutionary constraints and function in the IDRs of multicellular organisms.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012028","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T17:52:14Z","timestamp":1714067534000},"page":"e1012028","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Evolutionary analyses of intrinsically disordered regions reveal widespread signals of conservation"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6407-3298","authenticated-orcid":true,"given":"Marc D.","family":"Singleton","sequence":"first","affiliation":[]},{"given":"Michael B.","family":"Eisen","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"pcbi.1012028.ref001","article-title":"The molecular basis for cellular function of intrinsically disordered protein regions","author":"AS Holehouse","year":"2023","journal-title":"Nature Reviews Molecular Cell Biology"},{"issue":"2","key":"pcbi.1012028.ref002","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.tibs.2011.11.002","article-title":"Intrinsic disorder: Signaling via highly specific but short-lived association","volume":"37","author":"HX Zhou","year":"2012","journal-title":"Trends in Biochemical Sciences"},{"issue":"1","key":"pcbi.1012028.ref003","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nrm3920","article-title":"Intrinsically disordered proteins in cellular signalling and regulation","volume":"16","author":"PE Wright","year":"2014","journal-title":"Nature Reviews Molecular Cell Biology"},{"issue":"20","key":"pcbi.1012028.ref004","doi-asserted-by":"crossref","first-page":"5129","DOI":"10.1111\/j.1742-4658.2005.04948.x","article-title":"Flexible nets. 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