Abstract
The evolutionary mechanisms leading to duplicate gene retention are well understood, but the long-term impacts of paralog differentiation on the regulation of metabolism remain underappreciated. Here we experimentally dissect the functions of two pairs of ancient paralogs of the GALactose sugar utilization network in two yeast species. We show that the Saccharomyces uvarum network is more active, even as over-induction is prevented by a second co-repressor that the model yeast Saccharomyces cerevisiae lacks. Surprisingly, removal of this repression system leads to a strong growth arrest, likely due to overly rapid galactose catabolism and metabolic overload. Alternative sugars, such as fructose, circumvent metabolic control systems and exacerbate this phenotype. We further show that S. cerevisiae experiences homologous metabolic constraints that are subtler due to how the paralogs have diversified. These results show how the functional differentiation of paralogs continues to shape regulatory network architectures and metabolic strategies long after initial preservation.
Article and author information
Author details
Funding
National Science Foundation (DEB-1253634 , DEB-1442148)
- Chris Todd Hittinger
National Institute of Food and Agriculture (Hatch Project 1003258)
- Chris Todd Hittinger
DOE Great Lakes Bioenergy Research Center (DOE Office of Science BER DE-FC02-07ER64494)
- Joshua J Coon
- Chris Todd Hittinger
Pew Charitable Trusts (Pew Scholar in the Biomedical Sciences)
- Chris Todd Hittinger
Alexander von Humboldt-Stiftung (Alfred Toepfer Faculty Fellow)
- Chris Todd Hittinger
National Institutes of Health (R35 GM118110)
- Joshua J Coon
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Leonid Kruglyak, Howard Hughes Medical Institute, Uuniversity of California, Los Angeles, United States
Publication history
- Received: June 21, 2016
- Accepted: September 28, 2016
- Accepted Manuscript published: September 30, 2016 (version 1)
- Accepted Manuscript updated: October 5, 2016 (version 2)
- Version of Record published: November 1, 2016 (version 3)
Copyright
© 2016, Kuang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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