1. Genetics and Genomics
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An incoherent feedforward loop facilitates adaptive tuning of gene expression

  1. Jungeui Hong
  2. Nathan Brandt
  3. Farah Abdual-Rahman
  4. Ally W H Yang
  5. Timothy R Hughes
  6. David Gresham  Is a corresponding author
  1. New York University, United States
  2. University of Toronto, Canada
Research Article
  • Cited 5
  • Views 3,430
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Cite this article as: eLife 2018;7:e32323 doi: 10.7554/eLife.32323

Abstract

We studied adaptive evolution of gene expression using long-term experimental evolution of Saccharomyces cerevisiae in ammonium-limited chemostats. We found repeated selection for non-synonymous variation in the DNA binding domain of the transcriptional activator, GAT1, which functions with the repressor, DAL80 in an incoherent type-1 feedforward loop (I1-FFL) to control expression of the high affinity ammonium transporter gene, MEP2. Missense mutations in the DNA binding domain of GAT1 reduce its binding to the GATAA consensus sequence. However, we show experimentally, and using mathematical modeling, that decreases in GAT1 binding result in increased expression of MEP2 as a consequence of properties of I1-FFLs. Our results show that I1-FFLs, one of the most commonly occurring network motifs in transcriptional networks, can facilitate adaptive tuning of gene expression through modulation of transcription factor binding affinities. Our findings highlight the importance of gene regulatory architectures in the evolution of gene expression.

Article and author information

Author details

  1. Jungeui Hong

    Department of Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Nathan Brandt

    Department of Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Farah Abdual-Rahman

    Department of Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ally W H Yang

    Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Timothy R Hughes

    Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. David Gresham

    Department of Biology, New York University, New York, United States
    For correspondence
    dgresham@nyu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4028-0364

Funding

National Science Foundation (MCB1244219)

  • David Gresham

National Institutes of Health (R01GM107466)

  • David Gresham

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

Reviewing Editor

  1. Naama Barkai, Weizmann Institute of Science, Israel

Publication history

  1. Received: September 26, 2017
  2. Accepted: April 4, 2018
  3. Accepted Manuscript published: April 5, 2018 (version 1)
  4. Version of Record published: April 17, 2018 (version 2)
  5. Version of Record updated: October 8, 2018 (version 3)

Copyright

© 2018, Hong 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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