Evolution of reduced co-activator dependence led to target expansion of a starvation response pathway

  1. Bin Z He  Is a corresponding author
  2. Xu Zhou
  3. Erin K O'Shea  Is a corresponding author
  1. Howard Hughes Medical Institute, Harvard University Faculty of Arts and Sciences Center for Systems Biology, United States
  2. Yale School of Medicine, United States

Abstract

Although combinatorial regulation is a common feature in gene regulatory networks, how it evolves and affects network structure and function is not well understood. In S. cerevisiae, the phosphate starvation (PHO) responsive transcription factors Pho4 and Pho2 are required for gene induction and survival during phosphate starvation. In the related human commensal C. glabrata, Pho4 is required but Pho2 is dispensable for survival in phosphate starvation and is only partially required for inducing PHO genes. Phylogenetic survey suggests that reduced dependence on Pho2 evolved in C. glabrata and closely related species. In S. cerevisiae, less Pho2-dependent Pho4 orthologs induce more genes. In C. glabrata, its Pho4 binds to more locations and induces three times as many genes as Pho4 in S. cerevisiae does. Our work shows how evolution of combinatorial regulation allows for rapid expansion of a gene regulatory network's targets, possibly extending its physiological functions.

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Author details

  1. Bin Z He

    Howard Hughes Medical Institute, Harvard University Faculty of Arts and Sciences Center for Systems Biology, Cambridge, United States
    For correspondence
    binhe@fas.harvard.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3072-6238
  2. Xu Zhou

    Yale School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1692-6823
  3. Erin K O'Shea

    Howard Hughes Medical Institute, Harvard University Faculty of Arts and Sciences Center for Systems Biology, Cambridge, United States
    For correspondence
    osheae@hhmi.org
    Competing interests
    Erin K O'Shea, Chief Scientific Officer and a Vice President at the Howard Hughes Medical Institute, one of the three founding funders of eLife..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2649-1018

Funding

Howard Hughes Medical Institute

  • Bin Z He
  • Xu Zhou
  • Erin K O'Shea

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

Copyright

© 2017, He 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. Bin Z He
  2. Xu Zhou
  3. Erin K O'Shea
(2017)
Evolution of reduced co-activator dependence led to target expansion of a starvation response pathway
eLife 6:e25157.
https://doi.org/10.7554/eLife.25157

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https://doi.org/10.7554/eLife.25157

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