The regulation of cellular growth and proliferation in response to environmental cues is critical for development and the maintenance of viability in all organisms. In unicellular organisms, such as the budding yeast Saccharomyces cerevisiae, growth and proliferation are regulated by nutrient availability. We have described changes in the pattern of protein synthesis during the growth of S. cerevisiae cells to stationary phase (E. K. Fuge, E. L. Braun, and M. Werner-Washburne, J. Bacteriol. 176:5802-5813, 1994) and noted a protein, which we designated Snz1p (p35), that shows increased synthesis after entry into stationary phase. We report here the identification of the SNZ1 gene, which encodes this protein. We detected increased SNZ1 mRNA accumulation almost 2 days after glucose exhaustion, significantly later than that of mRNAs encoded by other postexponential genes. SNZ1-related sequences were detected in phylogenetically diverse organisms by sequence comparisons and low-stringency hybridization. Multiple SNZ1-related sequences were detected in some organisms, including S. cerevisiae. Snz1p was found to be among the most evolutionarily conserved proteins currently identified, indicating that we have identified a novel, highly conserved protein involved in growth arrest in S. cerevisiae. The broad phylogenetic distribution, the regulation of the SNZ1 mRNA and protein in S. cerevisiae, and identification of a Snz protein modified during sporulation in the gram-positive bacterium Bacillus subtilis support the hypothesis that Snz proteins are part of an ancient response that occurs during nutrient limitation and growth arrest.The proper regulation of cellular proliferation and growth in response to extracellular cues is critical for development and the maintenance of viability in all organisms (4,45,75,76). The primary regulators of cellular growth and proliferation in multicellular organisms are growth factors and hormones, and the loss of this regulation may lead to neoplasia (4). Similar regulation of growth and proliferation exists in unicellular organisms, such as the budding yeast Saccharomyces cerevisiae, but nutrient availability is typically the most important extracellular cue in unicellular organisms (4,45,75,76). Given the universal distribution of mechanisms for regulating cellular growth and proliferation and the obvious selective advantage of proper growth regulation, it is likely that the last common ancestor of all organisms, termed the cenancestor (22, 26), also had mechanisms to control growth and proliferation in response to nutrient limitation.Aspects of general stress responses, such as the heat shock response, are distributed universally among organisms (18,47). During the heat shock response, synthesis of specific evolutionarily conserved proteins increases (8,15,18,36,47). The increased synthesis of the heat shock proteins occurs in response to increased temperature and other stresses in all three phylogenetic domains (defined in reference 80), suggesting that the heat shock response in ex...