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Coordination of Growth Rate, Cell Cycle, Stress Response, and Metabolic Activity in Yeast
Open accessAbstract
We studied the relationship between growth rate and genome-wide gene expression, cell cycle progression, and glucose metabolism in 36 steady-state continuous cultures limited by one of six different nutrients (glucose, ammonium, sulfate, phosphate, uracil, or leucine). The expression of more than one quarter of all yeast genes is linearly correlated with growth rate, independent of the limiting nutrient. The subset of negatively growth-correlated genes is most enriched for peroxisomal functions, whereas positively correlated genes mainly encode ribosomal functions. Many (not all) genes associated with stress response are strongly correlated with growth rate, as are genes that are periodically expressed under conditions of metabolic cycling. We confirmed a linear relationship between growth rate and the fraction of the cell population in the G0/G1 cell cycle phase, independent of limiting nutrient. Cultures limited by auxotrophic requirements wasted excess glucose, whereas those limited on phosphate, sulfate, or ammonia did not; this phenomenon (reminiscent of the “Warburg effect” in cancer cells) was confirmed in batch cultures. Using an aggregate of gene expression values, we predict (in both continuous and batch cultures) an “instantaneous growth rate.” This concept is useful in interpreting the system-level connections among growth rate, metabolism, stress, and the cell cycle.
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High mutation rates and mutator strains can emerge naturally during laboratory evolution and contribute to the formation of genetic novelty.
“Interestingly, it was shown that high mutation rates and mutator strains can emerge naturally during laboratory evolution and contribute to the formation of genetic novelty [33,73,139-141].”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [141]
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Metadata
- Authors
- Brauer, M. J., Huttenhower, C., Airoldi, E. M., Rosenstein, R., Matese, J. C., Gresham, D., Boer, V. M., Troyanskaya, O. G., & Botstein, D.
- Affiliations
- Princeton University (US)
- *Lewis-Sigler Institute for Integrative Genomics and
- ORCID
- Venue
- Molecular Biology of the Cell
- Published
- 2008-01
- Volume
- 19
- Issue
- 1
- Pages
- 352-367
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2174172
- OpenAlex
- W2098066769
- Cited by
- 558
- References
- 65
- Citations by year
- 2026: 18 · 2025: 15 · 2024: 14 · 2023: 25 · 2022: 28 · 2021: 27 · 2020: 25 · 2019: 32 · 2018: 30 · 2017: 27 · 2016: 34 · 2015: 43 · 2014: 46 · 2013: 34 · 2012: 45
- FWCI
- 9.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Science Foundation (CAREER, 0546275)
- National Institutes of Health
- National Human Genome Research Institute (HG-002649, F32HG002649)
- National Institute of General Medical Sciences (GM071508, R01GM071966, GM46406, R37GM046406, R01GM046406, R01GM107466, P50GM071508)
- 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 › Microbial Metabolic Engineering and Bioproduction
- Keywords
- growth rate, Saccharomyces cerevisiae, gene expression, cell cycle, glucose metabolism, nutrient limitation, stress response, peroxisomes, ribosomal genes, G0/G1 phase, Warburg effect, instantaneous growth rate, continuous culture, batch culture
- MeSH terms
- Ethanol, Cell Cycle, Culture Media, Food, Genes, Fungal, Glucose, Models, Biological, Regression Analysis, Saccharomyces cerevisiae, Transcription, Genetic, Gene Expression Regulation, Fungal, Cluster Analysis
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