Evolution of the complex transcription network controlling biofilm formation in Candida species

  1. Eugenio Mancera  Is a corresponding author
  2. Isabel Nocedal
  3. Stephen Hammel
  4. Megha Gulati
  5. Kaitlin F Mitchell
  6. David R Andes
  7. Clarissa J Nobile
  8. Geraldine Butler
  9. Alexander D Johnson
  1. Centro de Investigación y de Estudios Avanzados, Unidad Irapuato, Mexico
  2. Massachusetts Institute of Technology, United States
  3. University College Cork, Ireland
  4. Cell Press, United States
  5. Centers for Disease Control and Prevention, United States
  6. University of Wisconsin, United States
  7. University of California, Merced, United States
  8. Conway Institute, University College Dublin, Ireland
  9. University of California, San Francisco, United States

Abstract

We examine how a complex transcription network composed of seven 'master' regulators and hundreds of target genes evolved over a span of approximately 70 million years. The network controls biofilm formation in several Candida species, a group of fungi that are present in humans both as constituents of the microbiota and as opportunistic pathogens. Using a variety of approaches, we observed two major types of changes that have occurred in the biofilm network since the four extant species we examined last shared a common ancestor. Master regulator 'substitutions' occurred over relatively long evolutionary times, resulting in different species having overlapping, but different sets of master regulators of biofilm formation. Second, massive changes in the connections between the master regulators and their target genes occurred over much shorter timescales. We believe this analysis is the first detailed, empirical description of how a complex transcription network has evolved.

Data availability

ChIP-Seq and microarray gene expression data has been deposited to the NCBI Gene Expression Omnibus (GEO) repository under Superseries GSE160783

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Eugenio Mancera

    Departamento de Ingeniería Genética, Centro de Investigación y de Estudios Avanzados, Unidad Irapuato, Irapuato, Mexico
    For correspondence
    eugenio.mancera@cinvestav.mx
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0146-8732
  2. Isabel Nocedal

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4706-1113
  3. Stephen Hammel

    The School of Computer Sciences and IT, University College Cork, Cork, Ireland
    Competing interests
    No competing interests declared.
  4. Megha Gulati

    Molecular Cell, Cell Press, Cambridge, United States
    Competing interests
    No competing interests declared.
  5. Kaitlin F Mitchell

    Center for Global Health, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    No competing interests declared.
  6. David R Andes

    Departments of Medicine and Medical Microbiology and Immunology, University of Wisconsin, Madison, United States
    Competing interests
    No competing interests declared.
  7. Clarissa J Nobile

    Molecular and Cell Biology, University of California, Merced, Merced, United States
    Competing interests
    Clarissa J Nobile, Clarissa J. Nobile and Alexander D. Johnson are cofounders of BioSynesis, Inc., a company developing diagnostics and therapeutics for biofilm formation..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0799-6499
  8. Geraldine Butler

    School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1770-5301
  9. Alexander D Johnson

    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
    Competing interests
    Alexander D Johnson, Clarissa J. Nobile and Alexander D. Johnson are cofounders of BioSynesis, Inc., a company developing diagnostics and therapeutics for biofilm formation..

Funding

Human Frontiers Science Program (LT000484/2012-L)

  • Eugenio Mancera

Pew Biomedical Schoolar Award

  • Clarissa J Nobile

Kamangar family endowed chair

  • Clarissa J Nobile

UC-MEXUS

  • Eugenio Mancera

CONACyT (CB-2016-01 282511)

  • Eugenio Mancera

Wellcome Trust Seed Award in Science (209077/Z/17/Z)

  • Eugenio Mancera

National Institute of Health (Ro1AI083311)

  • Alexander D Johnson

National Institute of Health (Ro1AI049187)

  • Alexander D Johnson

National Institute of Health (Ro1AI073289)

  • David R Andes

National Institute of Health (R35GM124594)

  • Clarissa J Nobile

National Institute of Health (R21AI125801)

  • Clarissa J Nobile

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

Ethics

Animal experimentation: Procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Wisconsin, Madison (protocol MV1947).

Reviewing Editor

  1. Christian R Landry, Université Laval, Canada

Publication history

  1. Received: November 6, 2020
  2. Accepted: April 6, 2021
  3. Accepted Manuscript published: April 7, 2021 (version 1)
  4. Version of Record published: April 26, 2021 (version 2)

Copyright

© 2021, Mancera 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. Eugenio Mancera
  2. Isabel Nocedal
  3. Stephen Hammel
  4. Megha Gulati
  5. Kaitlin F Mitchell
  6. David R Andes
  7. Clarissa J Nobile
  8. Geraldine Butler
  9. Alexander D Johnson
(2021)
Evolution of the complex transcription network controlling biofilm formation in Candida species
eLife 10:e64682.
https://doi.org/10.7554/eLife.64682

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    Gene duplication is crucial to generating novel signaling pathways during evolution. However, it remains unclear how the redundant proteins produced by gene duplication ultimately acquire new interaction specificities to establish insulated paralogous signaling pathways. Here, we used ancestral sequence reconstruction to resurrect and characterize a bacterial two-component signaling system that duplicated in α-proteobacteria. We determined the interaction specificities of the signaling proteins that existed before and immediately after this duplication event and then identified key mutations responsible for establishing specificity in the two systems. Just three mutations, in only two of the four interacting proteins, were sufficient to establish specificity of the extant systems. Some of these mutations weakened interactions between paralogous systems to limit crosstalk. However, others strengthened interactions within a system, indicating that the ancestral interaction, although functional, had the potential to be strengthened. Our work suggests that protein-protein interactions with such latent potential may be highly amenable to duplication and divergence.

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