Afanasyeva, A., Bockwoldt, M., Cooney, C. et al. (2 more authors) (2018) Human long intrinsically disordered protein regions are frequent targets of positive selection. Genome research, 28 (7). pp. 975-982. ISSN 1088-9051
Abstract
Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher-order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here we address this question by investigating the evolutionary pattern of more than 6,600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a-priori knowledge of disordered protein regions and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs 4-fold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Authors. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Animal and Plant Sciences (Sheffield) |
Funding Information: | Funder Grant number LEVERHULME TRUST (THE) ECF-2015-453 NATURAL ENVIRONMENT RESEARCH COUNCIL NE/N013832/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Jun 2018 15:28 |
Last Modified: | 20 Apr 2021 08:43 |
Status: | Published |
Publisher: | Cold Spring Harbor Laboratory Press |
Refereed: | Yes |
Identification Number: | 10.1101/gr.232645.117 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:131675 |