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Yeast cells grown in culture can spontaneously synchronize their respiration,metabolism, gene expression and cell division. Such metabolic oscillations insynchronized cultures reflect single-cell oscillations, but the relationshipbetween the oscillations in single cells and synchronized cultures is poorlyunderstood. To understand this relationship and the coordination betweenmetabolism and cell division, we collected and analyzed DNA-content,gene-expression and physiological data, at hundreds of time-points, fromcultures metabolically-synchronized at different growth rates, carbon sourcesand biomass densities. The data enabled us to extend and generalize anensemble-average-over-phases (EAP) model that connects the population-averagegene-expression of asynchronous cultures to the gene-expression dynamics in thesingle-cells comprising the cultures. The extended model explains thecarbon-source specific growth-rate responses of hundreds of genes. Our datademonstrate that for a given growth rate, the frequency of metabolic cycling insynchronized cultures increases with the biomass density. This observationunderscores the difference between metabolic cycling in synchronized culturesand in single cells and suggests entraining of the single-cell cycle by aquorum-sensing mechanism. Constant levels of residual glucose during themetabolic cycling of synchronized cultures indicate that storage carbohydratesare required to fuel not only the G1/S transition of the division cycle butalso the metabolic cycle. Despite the large variation in profiled conditionsand in the time-scale of their dynamics, most genes preserve invariant dynamicsof coordination with each other and with the rate of oxygen consumption.Similarly, the G1/S transition always occurs at the beginning, middle or end ofthe high oxygen consumption phases, analogous to observations in human anddrosophila cells.

Extensive regulation of metabolism and growth during the cell division cycle