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MBC in Press, published online ahead of print October 24, 2007
Mol. Biol. Cell 10.1091/mbc.E07-08-0779

A more recent version of this article appeared on January 1, 2008
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Submitted on August 14, 2007
Revised on October 4, 2007
Accepted on October 11, 2007

Coordination of Growth Rate, Cell Cycle, Stress Response, and Metabolic Activity in Yeast

Matthew J. Brauer,*{dagger} Curtis Huttenhower,{ddagger}{sect} Edoardo M. Airoldi,{ddagger}{sect} Rachel Rosenstein,|| John C. Matese,¶ David Gresham,* Viktor M. Boer,* Olga G. Troyanskaya,{ddagger} and David Botstein*

Lewis-Sigler Institute for Integrative Genomics and Departments of *Molecular Biology and {ddagger}Computer Science, Princeton University, Princeton, NJ 08544; ||School of Medicine, Yale University, New Haven, CT 06510

Monitoring Editor: Thomas Fox

We studied the relation 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 a quarter of all yeast genes is linearly correlated with growth rate, independently 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.

{sect}These authors contributed equally to this work.

{dagger}Present address: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080.

Address correspondence to: David Botstein (botstein{at}princeton.edu)




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