Evolutionary changes in transcription factor coding sequence quantitatively alter sensory organ development and function

  1. Simon Weinberger
  2. Matthew P Topping
  3. Jiekun Yan
  4. Annelies Claeys
  5. Natalie De Geest
  6. Duru Ozbay
  7. Talah Hassan
  8. Xiaoli He
  9. Joerg T Albert
  10. Bassem A Hassan  Is a corresponding author
  11. Ariane Ramaekers  Is a corresponding author
  1. VIB Center for the Biology of Disease, Belgium
  2. University College London, United Kingdom
  3. ICM, France

Abstract

'Toolkit' genes are highly conserved developmental regulators. While changes in their regulatory elements contribute to morphological evolution, the role of coding sequence (CDS) evolution remains unresolved. We used CDS-specific knock-ins of the proneural transcription factor Atonal homologs (ATHs) to address this question. Drosophila Atonal CDS was endogenously replaced with that of distant ATHs at key phylogenetic positions, non-ATH proneural genes, and the closest CDS to ancestral proneural genes. ATHs and the ancestral-like gene rescued sensory organ fate in atonal mutants, in contrast to non-ATHs. Surprisingly, different ATHs displayed a gradient of quantitative variation in proneural activity and the number and functionality of sense organs. This proneural potency gradient correlated directly with ATH protein stability, including in response to Notch signaling, independently of mRNA levels or codon usage. This establishes a distinct and ancient function for ATHs and demonstrates that CDS evolution can underlie quantitative variation in sensory development and function.

Article and author information

Author details

  1. Simon Weinberger

    VIB Center for the Biology of Disease, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  2. Matthew P Topping

    Ear Institute, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Jiekun Yan

    VIB Center for the Biology of Disease, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Annelies Claeys

    VIB Center for the Biology of Disease, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  5. Natalie De Geest

    VIB Center for the Biology of Disease, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. Duru Ozbay

    VIB Center for the Biology of Disease, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  7. Talah Hassan

    Ear Institute, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Xiaoli He

    Ear Institute, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Joerg T Albert

    Ear Institute, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Bassem A Hassan

    Brain Development, ICM, Paris, France
    For correspondence
    bassem.hassan@icm-institute.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9533-4908
  11. Ariane Ramaekers

    VIB Center for the Biology of Disease, Leuven, Belgium
    For correspondence
    ariane.ramaekers@icm-institute.org
    Competing interests
    The authors declare that no competing interests exist.

Funding

Vlaams Instituut voor Biotechnologie

  • Simon Weinberger
  • Jiekun Yan
  • Annelies Claeys
  • Natalie De Geest
  • Duru Ozbay
  • Bassem A Hassan
  • Ariane Ramaekers

Fonds Wetenschappelijk Onderzoek

  • Simon Weinberger
  • Jiekun Yan
  • Annelies Claeys
  • Natalie De Geest
  • Duru Ozbay
  • Bassem A Hassan
  • Ariane Ramaekers

BELSPO

  • Simon Weinberger
  • Jiekun Yan
  • Annelies Claeys
  • Natalie De Geest
  • Duru Ozbay
  • Bassem A Hassan
  • Ariane Ramaekers

European Commission

  • Simon Weinberger
  • Bassem A Hassan

Human Frontier Science Program

  • Matthew P Topping
  • Talah Hassan
  • Xiaoli He
  • Joerg T Albert

Biotechnology and Biological Sciences Research Council

  • Matthew P Topping
  • Talah Hassan
  • Xiaoli He
  • Joerg T Albert

Paul G. Allen Family Foundation

  • Bassem A Hassan

Einstein Stiftung Berlin

  • Bassem A Hassan

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

Reviewing Editor

  1. Hugo J Bellen, Baylor College of Medicine, United States

Publication history

  1. Received: February 27, 2017
  2. Accepted: March 27, 2017
  3. Accepted Manuscript published: April 13, 2017 (version 1)
  4. Version of Record published: May 15, 2017 (version 2)

Copyright

© 2017, Weinberger 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. Simon Weinberger
  2. Matthew P Topping
  3. Jiekun Yan
  4. Annelies Claeys
  5. Natalie De Geest
  6. Duru Ozbay
  7. Talah Hassan
  8. Xiaoli He
  9. Joerg T Albert
  10. Bassem A Hassan
  11. Ariane Ramaekers
(2017)
Evolutionary changes in transcription factor coding sequence quantitatively alter sensory organ development and function
eLife 6:e26402.
https://doi.org/10.7554/eLife.26402

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