1. Genetics and Genomics

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
https://doi.org/10.7554/eLife.32323
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  1. Jungeui Hong
  2. Nathan Brandt
  3. Farah Abdual-Rahman
  4. Ally W H Yang
  5. Timothy R Hughes
  6. David Gresham
(2018)
An incoherent feedforward loop facilitates adaptive tuning of gene expression
eLife 7:e32323.
https://doi.org/10.7554/eLife.32323
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  3. Download .RIS

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.

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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.

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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  1. Jungeui Hong
  2. Nathan Brandt
  3. Farah Abdual-Rahman
  4. Ally W H Yang
  5. Timothy R Hughes
  6. David Gresham
(2018)
An incoherent feedforward loop facilitates adaptive tuning of gene expression
eLife 7:e32323.
https://doi.org/10.7554/eLife.32323

Share this article

https://doi.org/10.7554/eLife.32323

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    Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations.

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    We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504).

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    Funding:

    This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.

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