Cited by 228Fungal and yeast genetics researchGene Regulatory Network AnalysisGenomics and Chromatin Dynamics

The evolution of combinatorial gene regulation in fungi

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Tuch, Brian B, Galgoczy, David J, Hernday, Aaron D, Li, Hao, Johnson, Alexander D·2008·PLoS Biology

Abstract

It is widely suspected that gene regulatory networks are highly plastic. The rapid turnover of transcription factor binding sites has been predicted on theoretical grounds and has been experimentally demonstrated in closely related species. We combined experimental approaches with comparative genomics to focus on the role of combinatorial control in the evolution of a large transcriptional circuit in the fungal lineage. Our study centers on Mcm1, a transcriptional regulator that, in combination with five cofactors, binds roughly 4% of the genes in Saccharomyces cerevisiae and regulates processes ranging from the cell-cycle to mating. In Kluyveromyces lactis and Candida albicans, two other hemiascomycetes, we find that the Mcm1 combinatorial circuits are substantially different. This massive rewiring of the Mcm1 circuitry has involved both substantial gain and loss of targets in ancient combinatorial circuits as well as the formation of new combinatorial interactions. We have dissected the gains and losses on the global level into subsets of functionally and temporally related changes. One particularly dramatic change is the acquisition of Mcm1 binding sites in close proximity to Rap1 binding sites at 70 ribosomal protein genes in the K. lactis lineage. Another intriguing and very recent gain occurs in the C. albicans lineage, where Mcm1 is found to bind in combination with the regulator Wor1 at many genes that function in processes associated with adaptation to the human host, including the white-opaque epigenetic switch. The large turnover of Mcm1 binding sites and the evolution of new Mcm1-cofactor interactions illuminate in sharp detail the rapid evolution of combinatorial transcription networks.

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Crossref · 10.1371/journal.pbio.0060038

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  • Changes in regulatory circuits that control gene expression are one of the major drivers of evolution.

    “Changes in the regulatory circuits that control gene expression are one of the major drivers of evolution”

    From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Tuch et al. 2008

    The Introduction describes changes in gene regulation as a potentially powerful mode of evolution and says their contribution to phenotypic variation has been demonstrated. The Discussion reports extensive rewiring of a fungal regulatory circuit. Neither passage establishes the stronger, unqualified claim that such changes are one of the major drivers of evolution generally. (LLM, conf=0.83)

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Research works printed but not linked: 1

  1. Ptashne M Gann A 2002 Genes & signals Cold Spring Harbor (New York) Cold Spring Harbor Laboratory Press xvi, 192 p. p.

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Authors
Tuch, B. B., Galgoczy, D. J., Hernday, A. D., Li, H., & Johnson, A. D.
Affiliations
University of California, San Francisco (US)
Corresponding author
  • Li, Hao
  • Johnson, Alexander D
Venue
PLoS Biology
Published
2008-02-26
Volume
6
Issue
2
Pages
e38
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
OpenAlex
W2084695584
Cited by
228
References
66
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 10 · 2017: 9 · 2016: 16 · 2015: 15 · 2014: 15 · 2013: 15 · 2012: 21
FWCI
13.70
Type
journal article
Language
en
Open access
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Science Foundation
  • Broad Institute
  • Joint Genome Institute
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
combinatorial gene regulation, transcription factor binding sites, MCM1, Rap1, Wor1, hemiascomycetes, Kluyveromyces lactis, Candida albicans, Saccharomyces cerevisiae, ribosomal protein genes, host adaptation, cofactor interactions
MeSH terms
Genes, Fungal, Species Specificity, Transcription Factors, Gene Expression Regulation, Enzymologic, Evolution, Molecular, Minichromosome Maintenance 1 Protein, Saccharomyces cerevisiae Proteins, Epigenesis, Genetic

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