Investigating noise regulators by experimental evolution in Saccharomyces cerevisiae

Non-genetic variations may contribute to expression noise at the transcript or protein levels, resulting in cell-to-cell heterogeneity within an isogenic population. While cells have developed strategies to reduce noise in some cellular functions, this heterogeneity can also facilitate different levels of regulation and provide evolutionary benefits in fluctuating environments. Although several general characteristics of cellular noise have been revealed, detailed molecular pathways underlying noise regulation remain elusive. Here, we established a dual-fluorescent reporter system in Saccharomyces cerevisiae and performed experimental evolution to search for mutations increasing the protein noise. We obtained five evolved clones with increased noise. By analyzing evolved cells using bulk segregant analysis coupled with whole-genome sequencing, several SNPs were identified as the causal mutations which led to noise increase.