Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network

Abstract
Data availability
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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.

Data availability

The following data sets were generated

1. Kuang MC
2. Hittinger T
(2016) RNA-Seq of Saccharomyces uvarum
Publicly available at the NCBI Short Read Archive (accession no: SRP077015).

http://www.ncbi.nlm.nih.gov/sra/SRP077015

Article and author information

Author details

Meihua Christina Kuang

Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3206-6525
Paul D Hutchins

Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Jason D Russell

Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Joshua J Coon

Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Chris Todd Hittinger

Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States

For correspondence
cthittinger@wisc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5088-7461

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.

Copyright

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.