Overexpression profiling reveals cellular requirements in context of genetic backgrounds and environments

Abstract

Overexpression due to copy number variation, promoter mutation, or aneuploidy is often observed, but its adaptive role is not clearly understood. Using a novel "overexpression profiling" method designated ADOPT, we systematically obtained genes whose overexpression was functionally adaptive (GOFAs) under stress conditions in budding yeast to elucidate the nature of adaptive overexpression. GOFAs obtained under heat, salt, and oxidative stress were unique genes that differed from known stress response genes. GOFAs under salt (NaCl) stress were genes involved in calcium homeostasis, reflecting the calcium deficiency of the medium. GOFAs from different genetic backgrounds and co-overexpressing strains revealed that calcium and potassium requirements in salt stress tolerance differ among strains, which is reflected. Profiling of the knockout collection suggested that the effect of calcium was to prevent mitochondrial outbursts. Mitochondria-enhancing GOFAs were adaptive only when calcium was sufficient and conversely non-adaptive in calcium deficiency, supporting the above hypothesis. Adaptive overexpression, thus, reflects the cellular requirements for maximizing the organism's adaptive capacity within a given environmental and genetic context.