An ultradian clock shapes genome expression in yeast.

Abstract

Cell biology has traditionally focused on where rather than when things happen inside cells. The fundamental biochemical activities of the cell have been sorted into spatial domains, with functions allotted to subcellular compartments that can either promote or inhibit molecular interaction. Important exceptions to this prominence of three dimensions have arisen in the areas of cell-division cycle research and studies of circadian (≈24-hr) rhythm. Here the emphasis has been distinctly time-oriented, and recent efforts have made use of powerful new strategies to develop temporal maps of gene expression and macromolecular assembly. Microarray analyses have exposed deeply rooted, cell-autonomous programs of timed gene activity, and in both areas sequential control is extensive. Circadian rhythms are associated with the ordered expression of 10% or more (see below) of the genome in Arabidopsis, Drosophila , and the mouse, and a comparable fraction of the genome appears to be regulated by the cell cycle in yeast (1–12). An even more pervasive system of temporal organization is now the subject of a study in this issue of PNAS by Klevecz et al. (13), who follow the yeast Saccharomyces cerevisiae . An initial search for clusters of gene expression that might support a well known ≈40-min respiratory cycle has instead revealed that ≈40-min rhythms are a genomewide phenomenon. Truly constitutive expression may not apply to any gene's activity in continuously grown, aerobic cultures of yeast. Respiratory oscillations have been observed in budding yeast for at least 30 years and are readily detected at higher cell densities in continuous culture. It has been proposed that a stage of ethanol metabolism may supply diffusible factors that effect synchrony (14). In addition to periodic fluctuations in the concentration of dissolved oxygen, NAD(P)H and reduced glutathione concentrations are rhythmic. Perturbations of the reduced glutathione concentration reset the phase …