1. Developmental Biology
  2. Evolutionary Biology
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Evolutionary emergence of Hairless as a novel component of the Notch signaling pathway

  1. Steve W Miller
  2. Artem Movsesyan
  3. Sui Zhang
  4. Rosa Fernández
  5. James W Posakony  Is a corresponding author
  1. University of California, San Diego, United States
  2. Center for Genomic Regulation, Spain
Research Article
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Cite this article as: eLife 2019;8:e48115 doi: 10.7554/eLife.48115

Abstract

Suppressor of Hairless [Su(H)], the transcription factor at the end of the Notch pathway in Drosophila, utilizes the Hairless protein to recruit two co-repressors, Groucho (Gro) and C-terminal Binding Protein (CtBP), indirectly. Hairless is present only in the Pancrustacea, raising the question of how Su(H) in other protostomes gains repressive function. We show that Su(H) from a wide array of arthropods, molluscs, and annelids includes motifs that directly bind Gro and CtBP; thus, direct co-repressor recruitment is ancestral in the protostomes. How did Hairless come to replace this ancestral paradigm? Our discovery of a protein (S-CAP) in Myriapods and Chelicerates that contains a motif similar to the Su(H)-binding domain in Hairless has revealed a likely evolutionary connection between Hairless and Metastasis-associated (MTA) protein, a component of the NuRD complex. Sequence comparison and widely conserved microsynteny suggest that S-CAP and Hairless arose from a tandem duplication of an ancestral MTA gene.

Article and author information

Author details

  1. Steve W Miller

    Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7610-6336
  2. Artem Movsesyan

    Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sui Zhang

    Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Rosa Fernández

    Bioinformatics and Genomics Unit, Center for Genomic Regulation, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. James W Posakony

    Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, United States
    For correspondence
    jposakony@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6377-1732

Funding

National Institute of General Medical Sciences (R01GM046993)

  • James W Posakony

National Institute of General Medical Sciences (R01GM120377)

  • James W Posakony

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

Reviewing Editor

  1. Patricia J Wittkopp, University of Michigan, United States

Publication history

  1. Received: May 3, 2019
  2. Accepted: September 23, 2019
  3. Accepted Manuscript published: September 23, 2019 (version 1)
  4. Version of Record published: October 4, 2019 (version 2)
  5. Version of Record updated: October 8, 2019 (version 3)

Copyright

© 2019, Miller 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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