The cell growth cycle: resource allocation and subcellular pattern formation in budding yeast

Abstract

Metabolic oscillations percolate throughout cellular physiology. The transcriptome oscillates between expression of genes encoding for biosynthesis and growth, and for catabolism and stress response. Long protein half-lives suppress effects on protein abundance level, and the function of periodic transcription remains elusive. We performed RNA-seq analysis during a dynamic state of the system. Short protein half-lives and high transcript abundance amplitude of sulfur uptake genes and carbonic anhydrase, and dynamic changes of pathway intermediates H₂S and CO₂ support a direct role of transcription in cycle dynamics. Substantial changes in the relative duration of expression of the antagonistic co-expression cohorts precede a system bifurcation to a longer period, supporting the idea of a function in cellular resource allocation. The pulse-width modulation model, a mathematical formulation of this idea, can explain a large body of published experimental data on the dependence of the cycle period on the culture growth rate. This pulse-like model of cell growth provides a first theoretical framework, where the phenomenon is understood as a mechanism of cellular resource allocation and protein homeostasis, and is applicable to circadian transcriptome dynamics from all domains of life.