Regulatory network structure determines patterns of intermolecular epistasis

  1. Mato Lagator
  2. Srdjan Sarikas
  3. Hande Acar
  4. Jonathan P Bollback
  5. Călin C Guet  Is a corresponding author
  1. Institute of Science and Technology Austria, Austria

Abstract

Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system, and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution.

Article and author information

Author details

  1. Mato Lagator

    Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7847-3594
  2. Srdjan Sarikas

    Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
  3. Hande Acar

    Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1986-9753
  4. Jonathan P Bollback

    Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Călin C Guet

    Department of Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    For correspondence
    calin@ist.ac.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6220-2052

Funding

Seventh Framework Programme (291734)

  • Mato Lagator

H2020 European Research Council (648440)

  • Jonathan P Bollback

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 23, 2017
  2. Accepted: November 10, 2017
  3. Accepted Manuscript published: November 13, 2017 (version 1)
  4. Version of Record published: November 22, 2017 (version 2)
  5. Version of Record updated: November 23, 2017 (version 3)

Copyright

© 2017, Lagator 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. Mato Lagator
  2. Srdjan Sarikas
  3. Hande Acar
  4. Jonathan P Bollback
  5. Călin C Guet
(2017)
Regulatory network structure determines patterns of intermolecular epistasis
eLife 6:e28921.
https://doi.org/10.7554/eLife.28921

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