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Proteome-wide signatures of function in highly diverged intrinsically disordered regions

View ORCID ProfileTaraneh Zarin, Bob Strome, Alex N Nguyen Ba, Simon Alberti, Julie D Forman-Kay, Alan M Moses
doi: https://doi.org/10.1101/578716
Taraneh Zarin
Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
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  • ORCID record for Taraneh Zarin
Bob Strome
Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
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Alex N Nguyen Ba
Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
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Simon Alberti
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, GermanyTechnische Universität Dresden, Center for Molecular and Cellular Bioengineering, Biotechnology Center, Dresden, Germany
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Julie D Forman-Kay
Program in Molecular Medicine, Hospital for Sick Children, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, Canada
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Alan M Moses
Department of Cell and Systems Biology, University of Toronto, Toronto, CanadaDepartment of Ecology and Evolutionary Biology, University of Toronto, Toronto, CanadaDepartment of Computer Science, University of Toronto, Toronto, Canada
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 16, 2019.
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Proteome-wide signatures of function in highly diverged intrinsically disordered regions
Taraneh Zarin, Bob Strome, Alex N Nguyen Ba, Simon Alberti, Julie D Forman-Kay, Alan M Moses
bioRxiv 578716; doi: https://doi.org/10.1101/578716
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Proteome-wide signatures of function in highly diverged intrinsically disordered regions
Taraneh Zarin, Bob Strome, Alex N Nguyen Ba, Simon Alberti, Julie D Forman-Kay, Alan M Moses
bioRxiv 578716; doi: https://doi.org/10.1101/578716

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