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).
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
Gene duplication drives evolution by providing raw material for proteins with novel functions. An influential hypothesis by Ohno (1970) posits that gene duplication helps genes tolerate new mutations and thus facilitates the evolution of new phenotypes. Competing hypotheses argue that deleterious mutations will usually inactivate gene duplicates too rapidly for Ohno’s hypothesis to work. We experimentally tested Ohno’s hypothesis by evolving one or exactly two copies of a gene encoding a fluorescent protein in Escherichia coli through several rounds of mutation and selection. We analyzed the genotypic and phenotypic evolutionary dynamics of the evolving populations through high-throughput DNA sequencing, biochemical assays, and engineering of selected variants. In support of Ohno’s hypothesis, populations carrying two gene copies displayed higher mutational robustness than those carrying a single gene copy. Consequently, the double-copy populations experienced relaxed purifying selection, evolved higher phenotypic and genetic diversity, carried more mutations and accumulated combinations of key beneficial mutations earlier. However, their phenotypic evolution was not accelerated, possibly because one gene copy rapidly became inactivated by deleterious mutations. Our work provides an experimental platform to test models of evolution by gene duplication, and it supports alternatives to Ohno’s hypothesis that point to the importance of gene dosage.
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