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      Short linear motifs – ex nihilo evolution of protein regulation

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          Abstract

          Short sequence motifs are ubiquitous across the three major types of biomolecules: hundreds of classes and thousands of instances of DNA regulatory elements, RNA motifs and protein short linear motifs (SLiMs) have been characterised. The increase in complexity of transcriptional, post-transcriptional and post-translational regulation in higher Eukaryotes has coincided with a significant expansion of motif use. But how did the eukaryotic cell acquire such a vast repertoire of motifs? In this review, we curate the available literature on protein motif evolution and discuss the evidence that suggests SLiMs can be acquired by mutations, insertions and deletions in disordered regions. We propose a mechanism of ex nihilo SLiM evolution – the evolution of a novel SLiM from “nothing” – adding a functional module to a previously non-functional region of protein sequence. In our model, hundreds of motif-binding domains in higher eukaryotic proteins connect simple motif specificities with useful functions to create a large functional motif space. Accessible peptides that match the specificity of these motif-binding domains are continuously created and destroyed by mutations in rapidly evolving disordered regions, creating a dynamic supply of new interactions that may have advantageous phenotypic novelty. This provides a reservoir of diversity to modify existing interaction networks. Evolutionary pressures will act on these motifs to retain beneficial instances. However, most will be lost on an evolutionary timescale as negative selection and genetic drift act on deleterious and neutral motifs respectively. In light of the parallels between the presented model and the evolution of motifs in the regulatory segments of genes and (pre-)mRNAs, we suggest our understanding of regulatory networks would benefit from the creation of a shared model describing the evolution of transcriptional, post-transcriptional and post-translational regulation.

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          TimeTree: a public knowledge-base of divergence times among organisms.

          Biologists and other scientists routinely need to know times of divergence between species and to construct phylogenies calibrated to time (timetrees). Published studies reporting time estimates from molecular data have been increasing rapidly, but the data have been largely inaccessible to the greater community of scientists because of their complexity. TimeTree brings these data together in a consistent format and uses a hierarchical structure, corresponding to the tree of life, to maximize their utility. Results are presented and summarized, allowing users to quickly determine the range and robustness of time estimates and the degree of consensus from the published literature. TimeTree is available at http://www.timetree.net
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            To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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                Author and article information

                Contributors
                norman.davey@ucd.ie
                mcyert@stanford.edu
                alan.moses@utoronto.ca
                Journal
                Cell Commun Signal
                Cell Commun. Signal
                Cell Communication and Signaling : CCS
                BioMed Central (London )
                1478-811X
                21 November 2015
                21 November 2015
                2015
                : 13
                : 43
                Affiliations
                [ ]Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Ireland
                [ ]Department of Biology, Stanford University, Stanford, CA 94305 USA
                [ ]Department of Cell & Systems Biology, University of Toronto, Toronto, Canada
                [ ]Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Canada
                Article
                120
                10.1186/s12964-015-0120-z
                4654906
                26589632
                ac154a2e-62d8-449e-8f60-cfeb25dffb49
                © Davey et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 21 June 2015
                : 13 November 2015
                Categories
                Review
                Custom metadata
                © The Author(s) 2015

                Cell biology
                motifs,short linear motifs,slims,cis-regulatory elements,rna motifs,evolution,modularity,protein evolution

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