Proteome-wide signatures of function in highly diverged intrinsically disordered regions
Intrinsically disordered regions make up a large part of the proteome, but the sequence-to-function relationship in these regions is poorly understood, in part because the primary amino acid sequences of these regions are poorly conserved in alignments. Here we use an evolutionary approach to detect...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/46883 |
| _version_ | 1811201303240507392 |
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| author | Taraneh Zarin Bob Strome Alex N Nguyen Ba Simon Alberti Julie D Forman-Kay Alan M Moses |
| author_facet | Taraneh Zarin Bob Strome Alex N Nguyen Ba Simon Alberti Julie D Forman-Kay Alan M Moses |
| author_sort | Taraneh Zarin |
| collection | DOAJ |
| description | Intrinsically disordered regions make up a large part of the proteome, but the sequence-to-function relationship in these regions is poorly understood, in part because the primary amino acid sequences of these regions are poorly conserved in alignments. Here we use an evolutionary approach to detect molecular features that are preserved in the amino acid sequences of orthologous intrinsically disordered regions. We find that most disordered regions contain multiple molecular features that are preserved, and we define these as ‘evolutionary signatures’ of disordered regions. We demonstrate that intrinsically disordered regions with similar evolutionary signatures can rescue function in vivo, and that groups of intrinsically disordered regions with similar evolutionary signatures are strongly enriched for functional annotations and phenotypes. We propose that evolutionary signatures can be used to predict function for many disordered regions from their amino acid sequences. |
| first_indexed | 2024-04-12T02:18:42Z |
| format | Article |
| id | doaj.art-1ef704afc0bf411db20f5fbcef6b58fb |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:18:42Z |
| publishDate | 2019-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1ef704afc0bf411db20f5fbcef6b58fb2022-12-22T03:52:10ZengeLife Sciences Publications LtdeLife2050-084X2019-07-01810.7554/eLife.46883Proteome-wide signatures of function in highly diverged intrinsically disordered regionsTaraneh Zarin0https://orcid.org/0000-0003-1253-3843Bob Strome1Alex N Nguyen Ba2Simon Alberti3https://orcid.org/0000-0003-4017-6505Julie D Forman-Kay4https://orcid.org/0000-0001-8265-972XAlan M Moses5https://orcid.org/0000-0003-3118-3121Department of Cell and Systems Biology, University of Toronto, Toronto, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, CanadaDepartment of Organismic and Evolutionary Biology, Harvard University, Cambridge, United StatesMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, Dresden, GermanyProgram in Molecular Medicine, Hospital for Sick Children, Toronto, Canada; Department of Biochemistry, University of Toronto, Toronto, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, Canada; Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Canada; Department of Computer Science, University of Toronto, Toronto, CanadaIntrinsically disordered regions make up a large part of the proteome, but the sequence-to-function relationship in these regions is poorly understood, in part because the primary amino acid sequences of these regions are poorly conserved in alignments. Here we use an evolutionary approach to detect molecular features that are preserved in the amino acid sequences of orthologous intrinsically disordered regions. We find that most disordered regions contain multiple molecular features that are preserved, and we define these as ‘evolutionary signatures’ of disordered regions. We demonstrate that intrinsically disordered regions with similar evolutionary signatures can rescue function in vivo, and that groups of intrinsically disordered regions with similar evolutionary signatures are strongly enriched for functional annotations and phenotypes. We propose that evolutionary signatures can be used to predict function for many disordered regions from their amino acid sequences.https://elifesciences.org/articles/46883evolutionpurifying selectionclusteringmitochondial targeting signalsunstructured proteinmolecular features |
| spellingShingle | Taraneh Zarin Bob Strome Alex N Nguyen Ba Simon Alberti Julie D Forman-Kay Alan M Moses Proteome-wide signatures of function in highly diverged intrinsically disordered regions eLife evolution purifying selection clustering mitochondial targeting signals unstructured protein molecular features |
| title | Proteome-wide signatures of function in highly diverged intrinsically disordered regions |
| title_full | Proteome-wide signatures of function in highly diverged intrinsically disordered regions |
| title_fullStr | Proteome-wide signatures of function in highly diverged intrinsically disordered regions |
| title_full_unstemmed | Proteome-wide signatures of function in highly diverged intrinsically disordered regions |
| title_short | Proteome-wide signatures of function in highly diverged intrinsically disordered regions |
| title_sort | proteome wide signatures of function in highly diverged intrinsically disordered regions |
| topic | evolution purifying selection clustering mitochondial targeting signals unstructured protein molecular features |
| url | https://elifesciences.org/articles/46883 |
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