Evolution of the complex transcription network controlling biofilm formation in Candida species
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
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Evolution of biofilm formation in CandidaNCBI Gene Expression Omnibus, GSE160783.
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Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicansNCBI Gene Expression Omnibus, GSE57451.
Article and author information
Author details
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.
Reviewing Editor
- Christian R Landry, Université Laval, Canada
Ethics
Animal experimentation: Procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Wisconsin, Madison (protocol MV1947).
Version history
- Received: November 6, 2020
- Accepted: April 6, 2021
- Accepted Manuscript published: April 7, 2021 (version 1)
- 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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