Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 19, Issue 1, Pages 352-367Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E07-08-0779
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Funding
- National Institute of General Medical Sciences Center for Quantitative Biology [GM-071508]
- National Institutes of Health [R01 GM-071966]
- National Science Foundation (NSF) [IS-0513352]
- NSF CAREER [DBI-0546275]
- [GM-46406]
- [HG-002649]
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [F32HG002649] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P50GM071508, R01GM046406, R37GM046406, R01GM071966] Funding Source: NIH RePORTER
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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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