Organisms need to have the ability to respond to external environmental changes and stresses in order to thrive in nature. Saccharomyces cerevisiae has the ability to respond to stresses through the environmental stress response (ESR), where the expression of stress defense genes is induced and the expression of genes involved in growth is reduced. Most of the current work examining stress-activated gene expression is done using laboratory strains of yeast. However, gene functions can vary in different genetic backgrounds, which is why it is important to explore the effects of natural variation. In this project, we transformed several different natural isolates of yeast have with a molecular barcoded yeast open reading frame (MoBY-ORF 2.0) high copy number plasmid library. These transformed wild strains were grown in the presence of various stresses (ethanol, salt, or DTT) to identify which high-copy number genes increase or decrease fitness during periods of stress. Of particular interest are high-copy number genes that have different effects on fitness in different wild isolates versus genes that produce common effects across many wild strains. Examination of the effects of gene amplification in natural yeast isolates could provide insight to the genetic diversity of the stress response and how natural variation relates to gene function.