Transcriptional rewiring over evolutionary timescales changes quantitative and qualitative properties of gene expression
Open accessAbstract
Evolutionary changes in transcription networks are an important source of diversity across species, yet the quantitative consequences of network evolution have rarely been studied. Here we consider the transcriptional ‘rewiring’ of the three GAL genes that encode the enzymes needed for cells to convert galactose to glucose. In Saccharomyces cerevisiae, the transcriptional regulator Gal4 binds and activates these genes. In the human pathogen Candida albicans (which last shared a common ancestor with S. cerevisiae some 300 million years ago), we show that different regulators, Rtg1 and Rtg3, activate the three GAL genes. Using single-cell dynamics and RNA-sequencing, we demonstrate that although the overall logic of regulation is the same in both species—the GAL genes are induced by galactose—there are major differences in both the quantitative response of these genes to galactose and in the position of these genes in the overall transcription network structure of the two species.
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Under all conditions tested, homozygous deletion of either RTG1 or RTG3 impaired growth to the same extent as homozygous deletion of both genes, consistent with their protein products functioning together as a complex.
“Under all conditions tested, homozygous deletion of either RTG1 or RTG3 impaired growth to the same extent as homozygous deletion of both genes, consistent with their protein products functioning together as a complex32,33.”
From Multifactor transcriptional control of alternative oxidase induction integrates diverse environmental inputs to enable fungal virulence (2023) · cites this paper as [32]
The Results section on identifying C. albicans regulators (page unavailable) reports severe growth defects for each single-gene deletion on galactose with Antimycin A and says the findings suggest Rtg1 and Rtg3 work together. It does not compare growth of either single deletion with the double deletion; it reports no growth defect for the single deletions on glucose with Antimycin A. The claim’s equal-extent and all-conditions assertions are therefore unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn C. albicans, the Rtg1/Rtg3 complex has been implicated in regulating the expression of genes involved in multiple metabolic and signaling pathways.
“In C. albicans, the Rtg1/Rtg3 complex has been implicated in regulating the expression of genes involved in multiple metabolic and signaling pathways32,33.”
From Multifactor transcriptional control of alternative oxidase induction integrates diverse environmental inputs to enable fungal virulence (2023) · cites this paper as [32]
The Results section ('Do Rtg1 and Rtg3 directly regulate the GAL genes in C. albicans?'; page unavailable) shows that Rtg1 and Rtg3 regulate three genes involved in galactose metabolism. The passages do not establish that they regulate genes across multiple metabolic and signaling pathways in C. albicans; the metabolic-signaling statement in the Results concerns S. cerevisiae. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn Candida albicans, the orthologs of Rtg1 and Rtg3 are implicated in the regulation of galactose metabolism genes (CaGAL1, CaGAL7, and CaGAL10), a function that in S. cerevisiae is performed by Gal4p instead.
“In Candida albicans, the orthologs of Rtg1 and Rtg3 are implicated in the regulation of galactose metabolism genes (CaGAL1, CaGAL7, and CaGAL10), a function that in S. cerevisiae is performed by Gal4p instead”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Dalal et al. 2016
Rtg transcription factors partially replace Gal4p of S. cerevisiae as regulators of galactose catabolism genes in cells with inhibited respiration.
“In a classic example of evolutionary rewiring of transcriptional control, they partially replace Gal4p of S. cerevisiae as the regulators of galactose catabolism genes in cells with inhibited respiration (Dalal et al. 2016; Sun et al. 2023).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Dalal et al. 2016
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References 113 · Cited by 62
- Authors
- Dalal, C. K., Zuleta, I. A., Mitchell, K. F., Andes, D. R., El-Samad, H., & Johnson, A. D.
- Affiliations
- University of California, San Francisco (US)
- QB3 (US)
- University of Wisconsin–Madison (US)
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
- Corresponding author
- Dalal, Chiraj K
- Johnson, Alexander D
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-09-10
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5067116
- OpenAlex
- W2519141471
- Cited by
- 62
- References
- 113
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 9 · 2023: 10 · 2022: 1 · 2021: 8 · 2020: 2 · 2019: 8 · 2018: 7 · 2017: 12
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Paul G. Allen Family Foundation
- National Institute of General Medical Sciences (P50 GM081879)
- National Institutes of Health (R01AI073289, R01AI049187)
- 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
- transcriptional reprogramming, transcriptional regulation, GAL genes, GAL4, galactose metabolism, Saccharomyces cerevisiae, Candida albicans, comparative genomics, single-cell dynamics, gene expression dynamics, transcriptional regulatory networks
- MeSH terms
- Candida albicans, Biological Evolution, Galactose, Glucose, Humans, Saccharomyces cerevisiae, Transcription, Genetic, Gene Expression Regulation, Fungal, Gene Regulatory Networks
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