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.
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
- Christian R Landry, Université Laval, Canada
Publication 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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Further reading
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- Evolutionary Biology
- Microbiology and Infectious Disease
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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- Evolutionary Biology
- Microbiology and Infectious Disease
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