Metabolic excretion associated with nutrient–growth dysregulation promotes the rapid evolution of an overt metabolic defect

Robin Green, Sonal, Lin Wang, Samuel F.M. Hart, Wenyun Lu, David Skelding, Justin C. Burton, Hanbing Mi, Aric Capel, Hung Alex Chen, Aaron Lin, Arvind R. Subramaniam, Joshua D. Rabinowitz, Wenying Shou

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


In eukaryotes, conserved mechanisms ensure that cell growth is coordinated with nutrient availability. Overactive growth during nutrient limitation (“nutrient–growth dysregulation”) can lead to rapid cell death. Here, we demonstrate that cells can adapt to nutrient–growth dysregulation by evolving major metabolic defects. Specifically, when yeast lysine-auxotrophic mutant lys encountered lysine limitation, an evolutionarily novel stress, cells suffered nutrient–growth dysregulation. A subpopulation repeatedly evolved to lose the ability to synthesize organosulfurs (lysorgS). Organosulfurs, mainly reduced glutathione (GSH) and GSH conjugates, were released by lys cells during lysine limitation when growth was dysregulated, but not during glucose limitation when growth was regulated. Limiting organosulfurs conferred a frequency-dependent fitness advantage to lysorgS by eliciting a proper slow growth program, including autophagy. Thus, nutrient–growth dysregulation is associated with rapid organosulfur release, which enables the selection of organosulfur auxotrophy to better tune cell growth to the metabolic environment. We speculate that evolutionarily novel stresses can trigger atypical release of certain metabolites, setting the stage for the evolution of new ecological interactions.

Original languageEnglish (US)
Article numbere3000757
JournalPLoS biology
Issue number8
StatePublished - Aug 2020

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience
  • General Agricultural and Biological Sciences


Dive into the research topics of 'Metabolic excretion associated with nutrient–growth dysregulation promotes the rapid evolution of an overt metabolic defect'. Together they form a unique fingerprint.

Cite this