Abstract

Innovations in metazoan development arise from evolutionary modification of gene regulatory networks (GRNs). We report widespread cryptic variation in the requirement for two key regulatory inputs, SKN-1/Nrf2 and MOM-2/Wnt, into the C. elegans endoderm GRN. While some natural isolates show a nearly absolute requirement for these two regulators, in others, most embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. We observe a reciprocal trend, in which genomic variants, or knockdown of endoderm regulatory genes, that result in a high SKN-1 requirement often show low MOM-2/Wnt requirement and vice-versa, suggesting that cryptic variation in the endoderm GRN may be tuned by opposing requirements for these two key regulatory inputs. These findings reveal that while the downstream components in the endoderm GRN are common across metazoan phylogeny, initiating regulatory inputs are remarkably plastic even within a single species.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Yamila N Torres Cleuren

    University of Auckland, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  2. Chee Kiang Ewe

    Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kyle C Chipman

    Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Emily R Mears

    University of Auckland, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  5. Cricket G Wood

    Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Coco Emma Alma Al-Alami

    University of Auckland, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  7. Melissa R Alcorn

    Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Thomas L Turner

    Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Pradeep M Joshi

    Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4220-0559
  10. Russell G Snell

    University of Auckland, Auckland, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  11. Joel H Rothman

    Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States
    For correspondence
    joel.rothman@lifesci.ucsb.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6844-1377

Funding

National Institutes of Health (1R01HD082347)

  • Joel H Rothman

National Institutes of Health (1R01HD081266)

  • Joel H Rothman

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

Reviewing Editor

  1. Antonis Rokas, Vanderbilt University, United States

Version history

  1. Received: May 6, 2019
  2. Accepted: August 15, 2019
  3. Accepted Manuscript published: August 15, 2019 (version 1)
  4. Version of Record published: September 20, 2019 (version 2)

Copyright

© 2019, Torres Cleuren 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. Yamila N Torres Cleuren
  2. Chee Kiang Ewe
  3. Kyle C Chipman
  4. Emily R Mears
  5. Cricket G Wood
  6. Coco Emma Alma Al-Alami
  7. Melissa R Alcorn
  8. Thomas L Turner
  9. Pradeep M Joshi
  10. Russell G Snell
  11. Joel H Rothman
(2019)
Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network
eLife 8:e48220.
https://doi.org/10.7554/eLife.48220

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