TY - JOUR TI - Natural variation in the consequences of gene overexpression and its implications for evolutionary trajectories AU - Robinson, DeElegant AU - Place, Michael AU - Hose, James AU - Jochem, Adam AU - Gasch, Audrey P A2 - Verstrepen, Kevin J A2 - Wittkopp, Patricia J VL - 10 PY - 2021 DA - 2021/08/02 SP - e70564 C1 - eLife 2021;10:e70564 DO - 10.7554/eLife.70564 UR - https://doi.org/10.7554/eLife.70564 AB - Copy number variation through gene or chromosome amplification provides a route for rapid phenotypic variation and supports the long-term evolution of gene functions. Although the evolutionary importance of copy-number variation is known, little is understood about how genetic background influences its tolerance. Here, we measured fitness costs of over 4000 overexpressed genes in 15 Saccharomyces cerevisiae strains representing different lineages, to explore natural variation in tolerating gene overexpression (OE). Strain-specific effects dominated the fitness costs of gene OE. We report global differences in the consequences of gene OE, independent of the amplified gene, as well as gene-specific effects that were dependent on the genetic background. Natural variation in the response to gene OE could be explained by several models, including strain-specific physiological differences, resource limitations, and regulatory sensitivities. This work provides new insight on how genetic background influences tolerance to gene amplification and the evolutionary trajectories accessible to different backgrounds. KW - gene overexpression KW - natural variation KW - copy number variation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -