Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution

Kuang, Meihua Christina; Kominek, Jacek; Alexander, William G.; Cheng, Jan-Fang; Wrobel, Russell L.; Hittinger, Chris Todd; Wittkopp, ed., Patricia

doi:10.1093/molbev/msy102

Title: Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution

Journal Article · Mon May 21 00:00:00 EDT 2018 · Molecular Biology and Evolution

DOI:https://doi.org/10.1093/molbev/msy102· OSTI ID:1630172

Kuang, Meihua Christina ^[1]; Kominek, Jacek ^[2]; Alexander, William G. ^[2]; Cheng, Jan-Fang ^[3]; Wrobel, Russell L. ^[2]; Hittinger, Chris Todd ^[4]; Wittkopp, ed., Patricia

Laboratory of Genetics, Genome Center of Wisconsin, J. F. Crow Institute for the Study of Evolution, Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI, Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI
Laboratory of Genetics, Genome Center of Wisconsin, J. F. Crow Institute for the Study of Evolution, Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI, DOE Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI
DOE Joint Genome Institute, Walnut Creek, CA
Laboratory of Genetics, Genome Center of Wisconsin, J. F. Crow Institute for the Study of Evolution, Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI, Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI, DOE Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI

Here, repeated evolutionary events imply underlying genetic constraints that can make evolutionary mechanisms predictable. Morphological traits are thought to evolve frequently through cis-regulatory changes because these mechanisms bypass constraints in pleiotropic genes that are reused during development. In contrast, the constraints acting on metabolic traits during evolution are less well studied. Here we show how a metabolic bottleneck gene has repeatedly adopted similar cis-regulatory solutions during evolution, likely due to its pleiotropic role integrating flux from multiple metabolic pathways. Specifically, the genes encoding phosphoglucomutase activity (PGM1/PGM2), which connect GALactose catabolism to glycolysis, have gained and lost direct regulation by the transcription factor Gal4 several times during yeast evolution. Through targeted mutations of predicted Gal4-binding sites in yeast genomes, we show this galactose-mediated regulation of PGM1/2 supports vigorous growth on galactose in multiple yeast species, including Saccharomyces uvarum and Lachancea kluyveri. Furthermore, the addition of galactose-inducible PGM1 alone is sufficient to improve the growth on galactose of multiple species that lack this regulation, including Saccharomyces cerevisiae. The strong association between regulation of PGM1/2 by Gal4 even enables remarkably accurate predictions of galactose growth phenotypes between closely related species. This repeated mode of evolution suggests that this specific cis-regulatory connection is a common way that diverse yeasts can govern flux through the pathway, likely due to the constraints imposed by this pleiotropic bottleneck gene. Since metabolic pathways are highly interconnected, we argue that cis-regulatory evolution might be widespread at pleiotropic genes that control metabolic bottlenecks and intersections.

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Research Organization:: Great Lakes Bioenergy Research Center (GLBRC), Madison, WI (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231; SC0018409; FC02-07ER64494

OSTI ID:: 1630172

Alternate ID(s):: OSTI ID: 1459509; OSTI ID: 1560555

Journal Information:: Molecular Biology and Evolution, Journal Name: Molecular Biology and Evolution Vol. 35 Journal Issue: 8; ISSN 0737-4038

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 14 works

Citation information provided by
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