A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes

  1. Michelle A Carmell  Is a corresponding author
  2. Gregoriy A Dokshin
  3. Helen Skaletsky
  4. Yueh-Chiang Hu
  5. Josien C van Wolfswinkel
  6. Kyomi J Igarashi
  7. Daniel W Bellott
  8. Michael Nefedov
  9. Peter W Reddien
  10. George C Enders
  11. Vladimir N Uversky
  12. Craig C Mello
  13. David C Page  Is a corresponding author
  1. Whitehead Institute, United States
  2. University of Massachusetts Medical School, United States
  3. Cincinnati Children's Hospital Medical Center, United States
  4. Yale University, United States
  5. University of Queensland, United States
  6. University of Kansas Medical Center, United States
  7. University of South Florida, United States

Abstract

The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals. Studies of Gcna-mutant C. elegans and mice indicate that GCNA has functioned in reproduction for at least 600 million years. Homology to IDR-containing proteins implicated in DNA damage repair suggests that GCNA proteins may protect the genomic integrity of cells carrying a heritable genome.

Article and author information

Author details

  1. Michelle A Carmell

    Whitehead Institute, Cambridge, United States
    For correspondence
    carmell@wi.mit.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Gregoriy A Dokshin

    RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Helen Skaletsky

    Whitehead Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yueh-Chiang Hu

    Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Josien C van Wolfswinkel

    MCDB, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4221-3218
  6. Kyomi J Igarashi

    Whitehead Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Daniel W Bellott

    Whitehead Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Michael Nefedov

    School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Peter W Reddien

    Whitehead Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5569-333X
  10. George C Enders

    Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Vladimir N Uversky

    Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Craig C Mello

    RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. David C Page

    Whitehead Institute, Cambridge, United States
    For correspondence
    dcpage@wi.mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9920-3411

Funding

Howard Hughes Medical Institute

  • Michelle A Carmell
  • Gregoriy A Dokshin
  • Helen Skaletsky
  • Yueh-Chiang Hu
  • Kyomi J Igarashi
  • Daniel W Bellott
  • Peter W Reddien
  • Craig C Mello

Life Sciences Research Foundation

  • Michelle A Carmell

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

Ethics

Animal experimentation: All mouse studies were performed using a protocol approved by the Committee on Animal Care at the Massachusetts Institute of Technology (Protocol number: 0714-074-17).

Reviewing Editor

  1. Yukiko M Yamashita, University of Michigan, United States

Version history

  1. Received: July 27, 2016
  2. Accepted: October 5, 2016
  3. Accepted Manuscript published: October 8, 2016 (version 1)
  4. Accepted Manuscript updated: October 21, 2016 (version 2)
  5. Version of Record published: November 7, 2016 (version 3)

Copyright

© 2016, Carmell 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. Michelle A Carmell
  2. Gregoriy A Dokshin
  3. Helen Skaletsky
  4. Yueh-Chiang Hu
  5. Josien C van Wolfswinkel
  6. Kyomi J Igarashi
  7. Daniel W Bellott
  8. Michael Nefedov
  9. Peter W Reddien
  10. George C Enders
  11. Vladimir N Uversky
  12. Craig C Mello
  13. David C Page
(2016)
A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes
eLife 5:e19993.
https://doi.org/10.7554/eLife.19993

Share this article

https://doi.org/10.7554/eLife.19993

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