Metabolic excretion associated with nutrient–growth dysregulation promotes the rapid evolution of an overt metabolic defect
| Autor: | Wenying Shou, David Skelding, Samuel F. M. Hart, Aric Capel, Aaron E. Lin, Sonal, Wenyun Lu, Hung Alex Chen, Hanbing Mi, Lin Wang, Robin Green, Arvind R. Subramaniam, Justin Burton, Joshua D. Rabinowitz |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Auxotrophy Lysine Mutant Biochemistry chemistry.chemical_compound Methionine 0302 clinical medicine Fungal Evolution Amino Acids Biology (General) Cell Death Organic Compounds Chemistry General Neuroscience Monosaccharides Adaptation Physiological Biological Evolution Glutathione Cell biology Cell metabolism Cell Processes Physical Sciences Basic Amino Acids General Agricultural and Biological Sciences Metabolic Networks and Pathways Research Article Cell Physiology Programmed cell death Nitrogen QH301-705.5 Autophagic Cell Death Saccharomyces cerevisiae Carbohydrates Mycology Biology Carbohydrate metabolism Research and Analysis Methods General Biochemistry Genetics and Molecular Biology Excretion 03 medical and health sciences Stress Physiological Autophagy Sulfur Containing Amino Acids Molecular Biology Techniques Molecular Biology Sirolimus General Immunology and Microbiology Cell growth Organic Chemistry Chemical Compounds Biology and Life Sciences Proteins Nutrients Cell Biology biology.organism_classification Yeast Cell Metabolism Glucose 030104 developmental biology Peptides Ribosomes 030217 neurology & neurosurgery Cloning |
| Zdroj: | PLoS Biology, Vol 18, Iss 8, p e3000757 (2020) PLoS Biology |
| ISSN: | 1545-7885 |
| DOI: | 10.1371/journal.pbio.3000757 |
| Popis: | 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 (lys−orgS−). 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 lys−orgS− 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. In eukaryotes, conserved mechanisms ensure that cell growth is tuned to nutrient availability. This study shows that when cells cannot do this, novel metabolic interactions can rapidly evolve, and metabolites released from some cells can open a new route for other cells to evolve advantageous metabolic defects that better tune growth. |
| Databáze: | OpenAIRE |
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