Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network.
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. 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. We further show thatS. cerevisiaeexperiences 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.
Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States.|Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, United States.|Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, United States.|JF Crow Institute for the Study of Evolution, University of Wisconsin-Madison, Madison, Madison, United States.|Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States.
Meihua Christina
0000-0003-3206-6525
MC
Kuang
Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States.|Department of Chemistry, University of Wisconsin-Madison, Madison, United States.|DOE Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, United States.
Paul D
PD
Hutchins
Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States.|DOE Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, United States.|Metabolism Research Group, Morgridge Institute for Research, Madison, United States.
Jason D
JD
Russell
Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States.|Department of Chemistry, University of Wisconsin-Madison, Madison, United States.|DOE Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, United States.|Metabolism Research Group, Morgridge Institute for Research, Madison, United States.|Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, United States.
Joshua J
JJ
Coon
Laboratory of Genetics, University of Wisconsin-Madison, Madison, United States.|Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, United States.|Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, United States.|JF Crow Institute for the Study of Evolution, University of Wisconsin-Madison, Madison, Madison, United States.|Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, United States.|DOE Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, United States.
Chris Todd
0000-0001-5088-7461
CT
Hittinger
D005632:Fructose / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D020131:Genes, Duplicate; D005800:Genes, Fungal; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D012440:Saccharomyces / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*
D005632:Fructose; D005690:Galactose
S. cerevisiae; Saccharomyces bayanus; Saccharomyces uvarum; evolutionary biology; galactose; gene duplication; gene network; genomics; sugar metabolism
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