Rxivist logo

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

By 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

Posted 17 Dec 2018
bioRxiv DOI: 10.1101/498543

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 sub-population repeatedly evolved to lose the ability to synthesize organosulfurs (lys-orgS-). Organosulfurs, mainly glutathione and glutathione 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. ### Competing Interest Statement The authors have declared no competing interest.

Download data

  • Downloaded 326 times
  • Download rankings, all-time:
    • Site-wide: 57,187 out of 101,046
    • In evolutionary biology: 3,772 out of 6,029
  • Year to date:
    • Site-wide: 32,357 out of 101,046
  • Since beginning of last month:
    • Site-wide: 32,072 out of 101,046

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News

  • 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
  • 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
  • 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
  • 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
  • 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
  • 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
  • 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
  • 22 Jan 2019: Nature just published an article about Rxivist and our data.
  • 13 Jan 2019: The Rxivist preprint is live!