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

  1. Taraneh Zarin
  2. Bob Strome
  3. Alex N Nguyen Ba
  4. Simon Alberti
  5. Julie Deborah Forman-Kay
  6. Alan M Moses  Is a corresponding author
  1. University of Toronto, Canada
  2. Harvard University, United States
  3. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  4. Hospital for Sick Children, Canada

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.

Data availability

The analysis is based on publically available sequence data from YGOB. Source data has been included as supplementary data.

Article and author information

Author details

  1. Taraneh Zarin

    Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Bob Strome

    Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Alex N Nguyen Ba

    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Simon Alberti

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4017-6505
  5. Julie Deborah Forman-Kay

    Program in Molecular Medicine, Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8265-972X
  6. Alan M Moses

    Department of Cell and Systems Biology, University of Toronto, Toronto, Canada
    For correspondence
    alan.moses@utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3118-3121

Funding

National Sciences and Engineering Research Council (Alexander Graham Bell Scholarship)

  • Taraneh Zarin

National Sciences and Engineering Research Council (Discovery Grant)

  • Alan M Moses

Canadian Institutes of Health Research (PJT-148532)

  • Julie Deborah Forman-Kay
  • Alan M Moses

Canadian Institutes of Health Research (FDN-148375)

  • Julie Deborah Forman-Kay

Canada Research Chairs

  • Julie Deborah Forman-Kay

Canadian Foundation for Innovation

  • Alan M Moses

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Michael B Eisen, HHMI, University of California, Berkeley, United States

Version history

  1. Received: March 15, 2019
  2. Accepted: July 1, 2019
  3. Accepted Manuscript published: July 2, 2019 (version 1)
  4. Version of Record published: July 16, 2019 (version 2)
  5. Version of Record updated: May 15, 2020 (version 3)
  6. Version of Record updated: June 3, 2020 (version 4)

Copyright

© 2019, Zarin et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Taraneh Zarin
  2. Bob Strome
  3. Alex N Nguyen Ba
  4. Simon Alberti
  5. Julie Deborah Forman-Kay
  6. Alan M Moses
(2019)
Proteome-wide signatures of function in highly diverged intrinsically disordered regions
eLife 8:e46883.
https://doi.org/10.7554/eLife.46883

Share this article

https://doi.org/10.7554/eLife.46883

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