## 4 Discussion
### Regulatory Network Responsible for the Cellular Switch from a Variable to a Stable Environment
Unlike the previous reports mentioned above, our data indicate that adaptation to a stable environment may not involve the accumulation of mutations, so it can be quickly reversed if the conditions become variable again. On the other hand, it seems rational that the changes increasing cell fitness in a stable, nonstressful environment must be slow because the cell must spend some time in such an environment before it is assured that the growth conditions are indeed stable and nonstressful. Such apparent purposefulness is explicable considering the stochastic nature of gene expression. It has been shown that within a genetically homogenous yeast cell population, certain genes, especially those responding to environmental changes, display high cell-to-cell variation in expression levels, termed transcriptional noise [37]. This phenomenon of heterogeneity of gene expression was later shown to be important for survival in conditions of variable nutrient availability [38; 39] or stressful environments [40; 41]. In addition to genes involved in nutrient assimilation or stress resistance, transcriptional noise is characteristic of genes encoding plasma membrane transporters [42]. Moreover, it is known that stress awareness can be inherited and that the memory of the response to environmental stresses is encoded epigenetically [43; 44]. It can be transmitted to offspring as chromatin modifications [45], such as tethering it to the nuclear envelope [46], by histone methylation [47] leading to heterochromatin formation [48], and by changing the nucleosome code [49]. It can also be transmitted by prion propagation [50; 51]. These memory records are subject to gradual modifications as the growth conditions change [51]; therefore, the prolonged growth of transcriptionally heterogeneous yeast cell populations in stable, nonstressful conditions will favor cells with lower expression of stress protecting genes whose products are becoming dispensable. This may result in a gradual decrease in their expression levels averaged across the cell population. We did not reveal the specific mechanism(s) pertinent to gene expression differences discovered in our study. However, we postulate that the differences observed by us during the cultivation of _S. cerevisiae_ cells in a stable, unchallenging milieu demonstrated the process of \"forgetting\" their previous experience of growth in variable and stressful conditions. Incidentally, mutational changes in microevolution experiments leading to the abandonment of network signaling circuits that are dispensable in a constant environment have been considered a manifestation of the myopic nature of evolution; these mutations put cells at a disadvantage when the environment becomes variable again [10]. Our data indicate that switching to a less resource-hungry lifestyle can occur without adaptive mutations and therefore is not so myopic because it can be easily reversed. To our knowledge, the phenomenon described in this paper has never been the subject of a standalone study; nevertheless, it was recently noticed by others in the course of a large-scale proteomic study [30]. The authors of that paper provide evidence that the gradual changes in protein levels as an adaptation to continuous culture conditions are not a consequence of adaptive mutations. Considering the gradual nature of adaptive changes, the authors suggest the epigenetic mechanism of this regulation [30] and emphasize the presence of a \"Histone modifier\" GO category among their proteins.