Fig. 2.

Mean-noise-fitness landscapes reveal gene-specific responses to expression deviations. a Keren, et al.²⁴ constructed yeast strains where in each strain one of a panel of genes (X, Y, Z,…) is driven by one of a panel of 120 synthetic promoters. All constructed strains were pooled and their fitness was measured in competitive growth experiments. b Relative mean expression strength of the synthetic promoters as well as the endogenous promoters of all investigated genes was measured by cloning each promoter in front of YFP in the HIS3 locus and assaying the resulting strains individually by flow cytometry²⁴. c Sharon, et al.³⁸ cloned synthetic promoters in front of YFP on a plasmid. Fluorescent activated cell sorting in combination with deep sequencing was used to infer mean expression and noise of individual promoters. d Fitness of synthetic promoter-gene strains plotted in mean—noise expression space for three example genes. Each panel shows the fitness (growth rate relative to wild-type, indicated by colour) of 79 yeast strains, in each of which a particular synthetic promoter drives the indicated gene, as a function of mean expression and noise of the synthetic promoters. Size of circles is inversely proportional to the measurement error of fitness. Error bars in horizontal and vertical directions indicate measurement error (s.e.m.) in mean and noise direction, respectively. Red vertical line shows estimated wild-type expression of the gene, dashed vertical lines mark region ± 1.5-fold from wild-type expression. Source data are provided as a Source Data file. e, Mean-noise-fitness landscapes were reconstructed using Gaussian smoothing on a regular grid, with fitness at each grid point as the weighted sum over the fitness of all strains. Weighting depends on distance to grid point (shown) and measurement errors in all three dimensions (see Methods). f Smoothed mean-noise-fitness landscapes of the three genes shown in panel d. Surface colour indicates fitness. Contour lines are spaced in increments of 0.01 fitness units. Strains (grey points), wild-type expression (red vertical line) and ± 1.5-fold around wild-type expression (grey vertical lines) are indicated. CV coefficient of variation, a.u. arbitrary units