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

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 theGALactose sugar utilization network in two yeast species. Here, we show that theSaccharomyces uvarumnetwork is more active, even as over-induction is prevented by a second co-repressor that the model yeastSaccharomyces cerevisiaelacks. 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. Furthermore, we show thatS. cerevisiaeexperiences homologous metabolic constraints that are subtler due to how the paralogs have diversified. Our results show how the functional differentiation of paralogs continues to shape regulatory network architectures and metabolic strategies long after initial preservation.

Authors:
ORCiD logo [1];  [2];  [3];  [4]; ORCiD logo [5]
  1. Univ. of Wisconsin, Madison, WI (United States). Lab. of Genetics, Wisconsin Energy Inst., JF Crow Inst. for the Study of Evolution and Genome Center of Wisconsin
  2. Univ. of Wisconsin, Madison, WI (United States). Genome Center of Wisconsin, Dept. of Chemistry, and DOE Great Lakes Bioenergy Research Center
  3. Univ. of Wisconsin, Madison, WI (United States). Genome Center of Wisconsin, DOE Great Lakes Bioenergy Research Center; Morgridge Inst. for Research, Madison, WI (United States)
  4. Univ. of Wisconsin, Madison, WI (United States). Genome Center of Wisconsin, Dept. of Chemistry, DOE Great Lakes Bioenergy Research Center, and Dept. of Biomolecular Chemistry; Morgridge Inst. for Research, Madison, WI (United States)
  5. Univ. of Wisconsin, Madison, WI (United States). Lab. of Genetics, Wisconsin Energy Inst., JF Crow Inst. for the Study of Evolution and Genome Center of Wisconsin, and DOE Great Lakes Bioenergy Research Center
Publication Date:
Research Org.:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1360719
Grant/Contract Number:
FC02-07ER64494
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Kuang, Meihua Christina, Hutchins, Paul D., Russell, Jason D., Coon, Joshua J., and Hittinger, Chris Todd. Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network. United States: N. p., 2016. Web. doi:10.7554/eLife.19027.
Kuang, Meihua Christina, Hutchins, Paul D., Russell, Jason D., Coon, Joshua J., & Hittinger, Chris Todd. Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network. United States. doi:10.7554/eLife.19027.
Kuang, Meihua Christina, Hutchins, Paul D., Russell, Jason D., Coon, Joshua J., and Hittinger, Chris Todd. 2016. "Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network". United States. doi:10.7554/eLife.19027. https://www.osti.gov/servlets/purl/1360719.
@article{osti_1360719,
title = {Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network},
author = {Kuang, Meihua Christina and Hutchins, Paul D. and Russell, Jason D. and Coon, Joshua J. and Hittinger, Chris Todd},
abstractNote = {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 theGALactose sugar utilization network in two yeast species. Here, we show that theSaccharomyces uvarumnetwork is more active, even as over-induction is prevented by a second co-repressor that the model yeastSaccharomyces cerevisiaelacks. 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. Furthermore, we show thatS. cerevisiaeexperiences homologous metabolic constraints that are subtler due to how the paralogs have diversified. Our results show how the functional differentiation of paralogs continues to shape regulatory network architectures and metabolic strategies long after initial preservation.},
doi = {10.7554/eLife.19027},
journal = {eLife},
number = ,
volume = 5,
place = {United States},
year = 2016,
month = 9
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 1work
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