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

PLoS Genet. 2023 Apr 28;19(4):e1010732. doi: 10.1371/journal.pgen.1010732. eCollection 2023 Apr.


Overexpression can help life adapt to stressful environments, making an examination of overexpressed genes valuable for understanding stress tolerance mechanisms. However, a systematic study of genes whose overexpression is functionally adaptive (GOFAs) under stress has yet to be conducted. We developed a new overexpression profiling method and systematically identified GOFAs in Saccharomyces cerevisiae under stress (heat, salt, and oxidative). Our results show that adaptive overexpression compensates for deficiencies and increases fitness under stress, like calcium under salt stress. We also investigated the impact of different genetic backgrounds on GOFAs, which varied among three S. cerevisiae strains reflecting differing calcium and potassium requirements for salt stress tolerance. Our study of a knockout collection also suggested that calcium prevents mitochondrial outbursts under salt stress. Mitochondria-enhancing GOFAs were only adaptive when adequate calcium was available and non-adaptive when calcium was deficient, supporting this idea. Our findings indicate that adaptive overexpression meets the cell's needs for maximizing the organism's adaptive capacity in the given environment and genetic context.

MeSH terms

  • Calcium
  • Genetic Background
  • Mitochondria / genetics
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae* / genetics


  • Calcium
  • Saccharomyces cerevisiae Proteins

Grants and funding

This work was partly supported by Ohsumi Frontier Science Foundation, JSPS KAKENHI Grant Numbers 18H04824 20H03242, and 20H04870 (H.M.), 21J12451 (N.S.), and 17H06411 (C.B. and Y.Y). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.