气候变化领域集成服务门户(CCPortal): Gene expression regulates metabolite homeostasis during the Crabtree effect: Implications for the adaptation and evolution of Metabolism

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DOI	10.1073/pnas.2014013118
	Gene expression regulates metabolite homeostasis during the Crabtree effect: Implications for the adaptation and evolution of Metabolism
	Rothman D.L.; Stearns S.C.; Shulman R.G.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	A key issue in both molecular and evolutionary biology has been to define the roles of genes and phenotypes in the adaptation of organisms to environmental changes. The dominant view has been that an organism's metabolic adaptations are driven by gene expression and that gene mutations, independent of the starting phenotype, are responsible for the evolution of new metabolic phenotypes. We propose an alternate hypothesis, in which the phenotype and genotype together determine metabolic adaptation both in the lifetime of the organism and in the evolutionary selection of adaptive metabolic traits. We tested this hypothesis by flux-balance and metabolic-control analysis of the relative roles of the starting phenotype and gene expression in regulating the metabolic adaptations during the Crabtree effect in yeast, when they are switched from a low- to high-glucose environment. Critical for successful short-term adaptation was the ability of the glycogen/trehalose shunt to balance the glycolytic pathway. The role of later gene expression of new isoforms of glycolytic enzymes, rather than flux control, was to provide additional homeostatic mechanisms allowing an increase in the amount and efficiency of adenosine triphosphate and product formation while maintaining glycolytic balance. We further showed that homeostatic mechanisms, by allowing increased phenotypic plasticity, could have played an important role in guiding the evolution of the Crabtree effect. Although our findings are specific to Crabtree yeast, they are likely to be broadly found because of the well-recognized similarities in glucose metabolism across kingdoms and phyla from yeast to humans. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Adaptation; Crabtree effect; Glucose metabolism; Glycogen shunt; Homeostasis
语种	英语
scopus关键词	adenosine triphosphate; glycogen; trehalose; Article; controlled study; Crabtree effect; enzyme activity; enzyme synthesis; evolutionary adaptation; FBP gene; fermentation; G6P genea; gene; gene expression regulation; gene mutation; genotype; glucose intake; glucose level; glucose metabolism; glycolysis; homeostasis; human; metabolic regulation; molecular biology; nonhuman; phenotype; phenotypic plasticity; priority journal; signal transduction
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181083
作者单位	Department of Radiology and Biomedical Engineering, Yale University, New Haven, CT 06520, United States; Magnetic Resonance Research Center, Yale University, New Haven, CT 06520, United States; Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06520, United States
推荐引用方式 GB/T 7714	Rothman D.L.,Stearns S.C.,Shulman R.G.. Gene expression regulates metabolite homeostasis during the Crabtree effect: Implications for the adaptation and evolution of Metabolism[J],2021,118(2).
APA	Rothman D.L.,Stearns S.C.,&Shulman R.G..(2021).Gene expression regulates metabolite homeostasis during the Crabtree effect: Implications for the adaptation and evolution of Metabolism.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Rothman D.L.,et al."Gene expression regulates metabolite homeostasis during the Crabtree effect: Implications for the adaptation and evolution of Metabolism".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).