ArticleMolecular biology and evolution2018
Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution.
Article in Molecular biology and evolution, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 49 citations in OpenAlex.
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- The Macroevolution of Filamentation Morphology Across thebioRxiv : the preprint server for biology · 2025Article
- Plasticity and environment-specific relationships between gene expression and fitness in Saccharomyces cerevisiae.Nature ecology & evolution · 2024Article
- Specialization Restricts the Evolutionary Paths Available to Yeast Sugar Transporters.Molecular biology and evolution · 2024Article
- Specialization restricts the evolutionary paths available to yeast sugar transporters.bioRxiv : the preprint server for biology · 2024Article
- Machine learning enables identification of an alternative yeast galactose utilization pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Plasticity and environment-specific relationships between gene expression and fitness inbioRxiv : the preprint server for biology · 2024Article
- NAC and Zuotin/Hsp70 chaperone systems coexist at the ribosome tunnel exit in vivo.Nucleic acids research · 2024Article
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- Oxygenation influences xylose fermentation and gene expression in the yeast genera Spathaspora and Scheffersomyces.Biotechnology for biofuels and bioproducts · 2024Article
- Taxogenomic analysis of a novel yeast species isolated from soil, Pichia galeolata sp. nov.Yeast (Chichester, England) · 2023Article
- Ploidy evolution in a wild yeast is linked to an interaction between cell type and metabolism.PLoS biology · 2023Article
- Enhancement of galactose uptake for bioethanol production from Eucheuma denticulatum hydrolysate using galactose-adapted yeasts.Bioprocess and biosystems engineering · 2023Article
- Strain-dependent differences in coordination of yeast signalling networks.The FEBS journal · 2023Article
- Expression inheritance and constraints on cis- and trans-regulatory mutations underlying lotus color variation.Plant physiology · 2023Article
- Macroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces.Nature communications · 2023Article
- Mechanisms of regulatory evolution in yeast.Current opinion in genetics & development · 2022Review
- Essentiality of Sis1, a J-domain protein Hsp70 cochaperone, can be overcome by Tti1, a specialized PIKK chaperone.Molecular biology of the cell · 2022Article
- The evolution of the GALactose utilization pathway in budding yeasts.Trends in genetics : TIG · 2022Review
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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