Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution
Abstract
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 amore »
- Authors:
-
- 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
- Publication Date:
- Research Org.:
- Great Lakes Bioenergy Research Center (GLBRC), Madison, WI (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1630172
- Alternate Identifier(s):
- OSTI ID: 1459509; OSTI ID: 1560555
- Grant/Contract Number:
- AC02-05CH11231; SC0018409; FC02-07ER64494
- Resource Type:
- Published Article
- Journal Name:
- Molecular Biology and Evolution
- Additional Journal Information:
- Journal Name: Molecular Biology and Evolution Journal Volume: 35 Journal Issue: 8; Journal ID: ISSN 0737-4038
- Publisher:
- Oxford University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; cis-regulatory evolution; CRISPR/Cas9; galactose; metabolism; gene network; phosphoglucomutase
Citation Formats
Kuang, Meihua Christina, Kominek, Jacek, Alexander, William G., Cheng, Jan-Fang, Wrobel, Russell L., Hittinger, Chris Todd, and Wittkopp, ed., Patricia. Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution. United States: N. p., 2018.
Web. doi:10.1093/molbev/msy102.
Kuang, Meihua Christina, Kominek, Jacek, Alexander, William G., Cheng, Jan-Fang, Wrobel, Russell L., Hittinger, Chris Todd, & Wittkopp, ed., Patricia. Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution. United States. https://doi.org/10.1093/molbev/msy102
Kuang, Meihua Christina, Kominek, Jacek, Alexander, William G., Cheng, Jan-Fang, Wrobel, Russell L., Hittinger, Chris Todd, and Wittkopp, ed., Patricia. Mon .
"Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution". United States. https://doi.org/10.1093/molbev/msy102.
@article{osti_1630172,
title = {Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution},
author = {Kuang, Meihua Christina and Kominek, Jacek and Alexander, William G. and Cheng, Jan-Fang and Wrobel, Russell L. and Hittinger, Chris Todd and Wittkopp, ed., Patricia},
abstractNote = {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.},
doi = {10.1093/molbev/msy102},
journal = {Molecular Biology and Evolution},
number = 8,
volume = 35,
place = {United States},
year = {Mon May 21 00:00:00 EDT 2018},
month = {Mon May 21 00:00:00 EDT 2018}
}
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https://doi.org/10.1093/molbev/msy102
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Cited by: 14 works
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Figures / Tables:
FIG. 1: Diagram of the GAL network in the budding yeast model S. cerevisiae and the role of Gal4-binding sites in explaining quantitative variation in growth on galactose. In the absence of galactose, the transcription factor Gal4 is inhibited by the corepressor Gal80, which prevents the expression of the GALactosemore »
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Works referenced in this record:
Specific DNA binding of GAL4, a positive regulatory protein of yeast
journal, April 1985
- Giniger, Edward; Varnum, Susan M.; Ptashne, Mark
- Cell, Vol. 40, Issue 4
Tinkering Evolution of Post-Transcriptional RNA Regulons: Puf3p in Fungi as an Example
journal, July 2010
- Jiang, Huifeng; Guan, Wenjun; Gu, Zhenglong
- PLoS Genetics, Vol. 6, Issue 7
Arboretum: Reconstruction and analysis of the evolutionary history of condition-specific transcriptional modules
journal, May 2013
- Roy, S.; Wapinski, I.; Pfiffner, J.
- Genome Research, Vol. 23, Issue 6
Beyond the Whole-Genome Duplication: Phylogenetic Evidence for an Ancient Interspecies Hybridization in the Baker's Yeast Lineage
journal, August 2015
- Marcet-Houben, Marina; Gabaldón, Toni
- PLOS Biology, Vol. 13, Issue 8
Evolution at Two Levels: On Genes and Form
journal, July 2005
- Carroll, Sean B.
- PLoS Biology, Vol. 3, Issue 7
PGM2 overexpression improves anaerobic galactose fermentation in Saccharomyces cerevisiae
journal, January 2010
- Garcia Sanchez, Rosa; Hahn-Hägerdal, Bärbel; Gorwa-Grauslund, Marie F.
- Microbial Cell Factories, Vol. 9, Issue 1
Reconstructing the Backbone of the Saccharomycotina Yeast Phylogeny Using Genome-Scale Data
journal, September 2016
- Shen, Xing-Xing; Zhou, Xiaofan; Kominek, Jacek
- G3: Genes|Genomes|Genetics, Vol. 6, Issue 12
A New System for Comparative Functional Genomics of Saccharomyces Yeasts
journal, July 2013
- Caudy, Amy A.; Guan, Yuanfang; Jia, Yue
- Genetics, Vol. 195, Issue 1
Escape from adaptive conflict after duplication in an anthocyanin pathway gene
journal, June 2008
- Des Marais, David L.; Rausher, Mark D.
- Nature, Vol. 454, Issue 7205
Adaptive Evolution of Metabolic Pathways in Drosophila
journal, March 2007
- Flowers, J.; Sezgin, E.; Kumagai, S.
- Molecular Biology and Evolution, Vol. 24, Issue 6
The Evolution of Control and Distribution of Adaptive Mutations in a Metabolic Pathway
journal, December 2009
- Wright, Kevin M.; Rausher, Mark D.
- Genetics, Vol. 184, Issue 2
phytools: an R package for phylogenetic comparative biology (and other things): phytools: R package
journal, December 2011
- Revell, Liam J.
- Methods in Ecology and Evolution, Vol. 3, Issue 2
Transcription of a yeast phosphoglucomutase isozyme gene is galactose inducible and glucose repressible.
journal, April 1990
- Oh, D.; Hopper, J. E.
- Molecular and Cellular Biology, Vol. 10, Issue 4
Causes and evolutionary significance of genetic convergence
journal, September 2010
- Christin, Pascal-Antoine; Weinreich, Daniel M.; Besnard, Guillaume
- Trends in Genetics, Vol. 26, Issue 9
Evo-Devo and an Expanding Evolutionary Synthesis: A Genetic Theory of Morphological Evolution
journal, July 2008
- Carroll, Sean B.
- Cell, Vol. 134, Issue 1
Transcriptional Rewiring of Fungal Galactose-Metabolism Circuitry
journal, June 2007
- Martchenko, Mikhail; Levitin, Anastasia; Hogues, Herve
- Current Biology, Vol. 17, Issue 12
Finding Functional Features in Saccharomyces Genomes by Phylogenetic Footprinting
journal, July 2003
- Cliften, P.
- Science, Vol. 301, Issue 5629
A Single Amino Acid Mutation Contributes to Adaptive Beach Mouse Color Pattern
journal, July 2006
- Hoekstra, Hopi E.; Hirschmann, Rachel J.; Bundey, Richard A.
- Science, Vol. 313, Issue 5783
Identifying Cis-Regulatory Changes Involved in the Evolution of Aerobic Fermentation in Yeasts
journal, May 2013
- Lin, Zhenguo; Wang, Tzi-Yuan; Tsai, Bing-Shi
- Genome Biology and Evolution, Vol. 5, Issue 6
GEIGER: investigating evolutionary radiations
journal, November 2007
- Harmon, L. J.; Weir, J. T.; Brock, C. D.
- Bioinformatics, Vol. 24, Issue 1
Transcriptional regulation in the yeast GAL gene family: a complex genetic network.
journal, June 1995
- Lohr, D.; Venkov, P.; Zlatanova, J.
- The FASEB Journal, Vol. 9, Issue 9
Unravelling evolutionary strategies of yeast for improving galactose utilization through integrated systems level analysis
journal, June 2011
- Hong, K. -K.; Vongsangnak, W.; Vemuri, G. N.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 29
Reconstruction of Ancestral Metabolic Enzymes Reveals Molecular Mechanisms Underlying Evolutionary Innovation through Gene Duplication
journal, December 2012
- Voordeckers, Karin; Brown, Chris A.; Vanneste, Kevin
- PLoS Biology, Vol. 10, Issue 12
Evolution of Flux Control in the Glucosinolate Pathway in Arabidopsis thaliana
journal, August 2012
- Olson-Manning, Carrie F.; Lee, Cheng-Ruei; Rausher, Mark D.
- Molecular Biology and Evolution, Vol. 30, Issue 1
PYD2 encodes 5,6-dihydropyrimidine amidohydrolase, which participates in a novel fungal catabolic pathway
journal, January 2000
- Gojkovic, Zoran; Jahnke, Karin; Schnackerz, Klaus D.
- Journal of Molecular Biology, Vol. 295, Issue 4
Remarkably ancient balanced polymorphisms in a multi-locus gene network
journal, February 2010
- Hittinger, Chris Todd; Gonçalves, Paula; Sampaio, José Paulo
- Nature, Vol. 464, Issue 7285
Stepwise Modification of a Modular Enhancer Underlies Adaptation in a Drosophila Population
journal, December 2009
- Rebeiz, M.; Pool, J. E.; Kassner, V. A.
- Science, Vol. 326, Issue 5960
Regulatory evolution of shavenbaby/ovo underlies multiple cases of morphological parallelism
journal, August 2003
- Sucena, Elio; Delon, Isabelle; Jones, Isaac
- Nature, Vol. 424, Issue 6951
Enzymatic assembly of DNA molecules up to several hundred kilobases
journal, April 2009
- Gibson, Daniel G.; Young, Lei; Chuang, Ray-Yuan
- Nature Methods, Vol. 6, Issue 5, p. 343-345
Evolution of gene network activity by tuning the strength of negative-feedback regulation
journal, February 2015
- Peng, Weilin; Liu, Ping; Xue, Yuan
- Nature Communications, Vol. 6, Issue 1
Sequencing and comparison of yeast species to identify genes and regulatory elements
journal, May 2003
- Kellis, Manolis; Patterson, Nick; Endrizzi, Matthew
- Nature, Vol. 423, Issue 6937
The genetic causes of convergent evolution
journal, October 2013
- Stern, David L.
- Nature Reviews Genetics, Vol. 14, Issue 11
Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene
journal, April 2006
- Prud'homme, Benjamin; Gompel, Nicolas; Rokas, Antonis
- Nature, Vol. 440, Issue 7087
The loci of Evolution: how Predictable is Genetic Evolution?
journal, September 2008
- Stern, David L.; Orgogozo, Virginie
- Evolution, Vol. 62, Issue 9
Genetic and Epigenetic Strategies Potentiate Gal4 Activation to Enhance Fitness in Recently Diverged Yeast Species
journal, December 2017
- Sood, Varun; Brickner, Jason H.
- Current Biology, Vol. 27, Issue 23
Comparative genomics of biotechnologically important yeasts
journal, August 2016
- Riley, Robert; Haridas, Sajeet; Wolfe, Kenneth H.
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 35
RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies
journal, January 2014
- Stamatakis, Alexandros
- Bioinformatics, Vol. 30, Issue 9
Rewiring of the Yeast Transcriptional Network Through the Evolution of Motif Usage
journal, August 2005
- Ihmels, J.
- Science, Vol. 309, Issue 5736
Molecular cloning and characterization of the pgm gene encoding phosphoglucomutase of Escherichia coli.
journal, September 1994
- Lu, M.; Kleckner, N.
- Journal of Bacteriology, Vol. 176, Issue 18
Parallel inactivation of multiple GAL pathway genes and ecological diversification in yeasts
journal, September 2004
- Hittinger, C. T.; Rokas, A.; Carroll, S. B.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 39
Molecular evidence for an ancient duplication of the entire yeast genome
journal, June 1997
- Wolfe, Kenneth H.; Shields, Denis C.
- Nature, Vol. 387, Issue 6634
Resurrecting ancestral alcohol dehydrogenases from yeast
journal, May 2005
- Thomson, J. Michael; Gaucher, Eric A.; Burgan, Michelle F.
- Nature Genetics, Vol. 37, Issue 6
The trehalose pathway and intracellular glucose phosphates as modulators of potassium transport and general cation homeostasis in yeast
journal, May 2004
- Mulet, Jose M.; Alejandro, Santiago; Romero, Carlos
- Yeast, Vol. 21, Issue 7
A new look at the statistical model identification
journal, December 1974
- Akaike, H.
- IEEE Transactions on Automatic Control, Vol. 19, Issue 6
Transcriptional rewiring over evolutionary timescales changes quantitative and qualitative properties of gene expression
journal, September 2016
- Dalal, Chiraj K.; Zuleta, Ignacio A.; Mitchell, Kaitlin F.
- eLife, Vol. 5
Coregulation of the Kluyveromyces lactis lactose permease and β-galactoidase genes is achieved by interaction of multiple LAC9 binding sites in a 2.6 kbp divergnent promoter
journal, January 1991
- Gödecke, A.; Zachariae, W.; Arvanitidis, A.
- Nucleic Acids Research, Vol. 19, Issue 19
Polygenic evolution of a sugar specialization trade-off in yeast
journal, February 2016
- Roop, Jeremy I.; Chang, Kyu Chul; Brem, Rachel B.
- Nature, Vol. 530, Issue 7590
Reconstruction of ancestral chromosome architecture and gene repertoire reveals principles of genome evolution in a model yeast genus
journal, May 2016
- Vakirlis, Nikolaos; Sarilar, Véronique; Drillon, Guénola
- Genome Research, Vol. 26, Issue 7
Composition of plant tissues and soil organic matter in the first stages of a vegetation succession
journal, March 2001
- Nierop, Klaas G. J.; van Lagen, Barend; Buurman, Peter
- Geoderma, Vol. 100, Issue 1-2
An autonomously replicating sequence for use in a wide range of budding yeasts
journal, December 2013
- Liachko, Ivan; Dunham, Maitreya J.
- FEMS Yeast Research, Vol. 14, Issue 2
Rapid Evolution of cis-Regulatory Sequences via Local Point Mutations
journal, September 2001
- Stone, Jonathon R.; Wray, Gregory A.
- Molecular Biology and Evolution, Vol. 18, Issue 9
Genome-Wide Location and Function of DNA Binding Proteins
journal, December 2000
- Ren, B.
- Science, Vol. 290, Issue 5500
HyPhy: hypothesis testing using phylogenies
journal, October 2004
- Pond, S. L. K.; Frost, S. D. W.; Muse, S. V.
- Bioinformatics, Vol. 21, Issue 5
Using Drosophila pigmentation traits to study the mechanisms of cis-regulatory evolution
journal, February 2017
- Rebeiz, Mark; Williams, Thomas M.
- Current Opinion in Insect Science, Vol. 19
High-Efficiency Genome Editing and Allele Replacement in Prototrophic and Wild Strains of Saccharomyces
journal, September 2014
- Alexander, W. G.; Doering, D. T.; Hittinger, C. T.
- Genetics, Vol. 198, Issue 3, p. 859-866
UniPROBE, update 2011: expanded content and search tools in the online database of protein-binding microarray data on protein-DNA interactions
journal, October 2010
- Robasky, K.; Bulyk, M. L.
- Nucleic Acids Research, Vol. 39, Issue Database
Saccharomyces Genome Database: the genomics resource of budding yeast
journal, November 2011
- Cherry, J. M.; Hong, E. L.; Amundsen, C.
- Nucleic Acids Research, Vol. 40, Issue D1
C4 Photosynthesis Evolved in Grasses via Parallel Adaptive Genetic Changes
journal, July 2007
- Christin, Pascal-Antoine; Salamin, Nicolas; Savolainen, Vincent
- Current Biology, Vol. 17, Issue 14
Efficient gene targeting inKluyveromyces lactis
journal, July 2004
- Kooistra, Rolf; Hooykaas, Paul J. J.; Steensma, H. Yde
- Yeast, Vol. 21, Issue 9
Gene duplication and the adaptive evolution of a classic genetic switch
journal, October 2007
- Hittinger, Chris Todd; Carroll, Sean B.
- Nature, Vol. 449, Issue 7163
Yeast Glycogen Synthase Kinase-3 Activates Msn2p-dependent Transcription of Stress Responsive Genes
journal, January 2003
- Hirata, Yuzoh; Andoh, Tomoko; Asahara, Toshimasa
- Molecular Biology of the Cell, Vol. 14, Issue 1
RELAX: Detecting Relaxed Selection in a Phylogenetic Framework
journal, December 2014
- Wertheim, Joel O.; Murrell, Ben; Smith, Martin D.
- Molecular Biology and Evolution, Vol. 32, Issue 3
Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity
journal, August 2013
- Rogers, William A.; Salomone, Joseph R.; Tacy, David J.
- PLoS Genetics, Vol. 9, Issue 8
A comparative analysis of the genetic switch between not-so-distant cousins: versus
journal, December 2005
- Rubiotexeira, M.
- FEMS Yeast Research, Vol. 5, Issue 12
Genetic Control of Phosphoglucomutase Variants in Saccharomyces cerevisiae
journal, January 1969
- Bevan, Patricia; Douglas, Howard C.
- Journal of Bacteriology, Vol. 98, Issue 2
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A Novel cis Element Achieves the Same Solution as an Ancestral cis Element During Thiamine Starvation in Candida glabrata
journal, November 2019
- Iosue, Christine L.; Gulotta, Anthony P.; Selhorst, Kathleen B.
- G3: Genes|Genomes|Genetics, Vol. 10, Issue 1
Natural Variation in the Multidrug Efflux Pump SGE1 Underlies Ionic Liquid Tolerance in Yeast
journal, July 2018
- Higgins, Douglas A.; Young, Megan K. M.; Tremaine, Mary
- Genetics, Vol. 210, Issue 1
Niche-specific metabolic adaptation in biotrophic and necrotrophic oomycetes is manifested in differential use of nutrients, variation in gene content, and enzyme evolution
journal, April 2019
- Ah-Fong, Audrey M. V.; Kagda, Meenakshi S.; Abrahamian, Melania
- PLOS Pathogens, Vol. 15, Issue 4
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