Natural Variation in the Fitness Consequences of Gene Amplification in Wild Saccharomyces cerevisiae Isolates [Bar-seq]

Genetic variation that underlies phenotypic differences provides the material on which evolutionary selection acts. Gene duplication/amplification is one type of genetic variation that can allow an organism to rapidly respond to environmental changes by increasing gene dosage. While the potential benefits afforded by gene amplification during evolution are well known, there is also a significant fitness cost to increasing gene dosage including resource shortages and burdening cellular systems. Although the evolutionary importance of gene duplication has long been appreciated, little is known about natural variation in the tolerance of duplication of specific genes. To investigate this question, we expressed the same high-copy gene overexpression (OE) library in a laboratory strain and 14 different wild S. cerevisiae isolates, together representing 4 lineages and several admixed strains, to explore the natural variation in tolerance to gene OE. Our results distinguish universal effects common to many studied strains versus strain-specific effects including broad-scale and gene-specific differences in the consequences of OE. These results raise important implications for the accessibility of evolutionary trajectories afforded by gene OE, depending on genetic background. We conducted a barcode sequencing experiment examining 15 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. Each strain was measured in biological triplicate for a total of 90 samples.