Natural variation in the consequences of gene overexpression during osmotic stress [BAR-Seq]
Free-living cells live in fluctuating environments and must be able to respond rapidly in order to survive. Genetic background can influence how an individual responds to a changing environment, including stressful changes. Changes in gene copy number can influence stress tolerance and responses, presumably due to corresponding changes in gene expression.  However, we recently showed that strains vary in their ability to tolerate gene copy number differences; how this influences variation in stress tolerance is relatively unknown. Here we measured the tolerance to gene overexpression (OE) in four different Saccharomyces cerevisiae strains, including wild isolates, when strains were grown under osmotic and ionic stress induced by sodium chloride (NaCl). OE genes that were deleterious to most strains under NaCl stress were enriched for translation processes, similar to the enrichments of deleterious genes in rich, non-stress medium. We found that the West African NCYC3290 strain and the North American YPS128 strain are more sensitive to NaCl stress than other strains. These strains showed the greatest number of sensitivities to gene OE compared to other strains. Although most genes were deleterious in these strains, subsets of genes are highly beneficial when OE during NaCl stress. Many of these highly beneficial genes are functionally related and point to underlying differences in strain physiology. This work illustrates how tolerance to gene overexpression is influenced by genotype-environment interactions. Overall design: We conducted a barcode sequencing experiment examining 4 yeast strains expressing a high copy number plasmid library. For each strain, we took samples at generation 0 (start of experiment) and generation 10  to quantify how plasmid abundance changes over time when strains were grown under osmotic and ionic stress induced by 0.7M of sodium chloride (NaCl). Each strain was measured in biological triplicate for a total of 24 samples.