Genetic Basis of Metabolome Variation in Yeast


Many traits, from human height to E. coli growth rate, quantitatively vary across members of a species. Among the most medically and agriculturally important traits are levels of cellular metabolites, such as cholesterol levels in humans or starch in food crops. Metabolic variation in yeast also holds practical importance with some Saccharomyces strains better suited to making ethanol for biofuel and others tailored to making flavorful wine. This metabolic heterogeneity can be used to gain insight into general principles of metabolic regulation which effect metabolite abundance in eukaryotes. To this end, we examined inter-strain differences in metabolism in over 100 closely related S. cerevisiae strains. We identified over 50 genetic loci that control the levels of specific metabolites, including not only loci that encode metabolic enzymes, but also those that encode global cellular regulators. For example, differences in the sequence of ira2, an inhibitor of Ras, lead to differences in central carbon metabolite levels, and polymorphisms in slt2, a poorly characterized MAP kinase, alter levels of sulfur-containing metabolites. These findings provide insights into the mechanisms cells use to control metabolite concentrations.


Vyšlo v časopise: Genetic Basis of Metabolome Variation in Yeast. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004142
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004142

Souhrn

Many traits, from human height to E. coli growth rate, quantitatively vary across members of a species. Among the most medically and agriculturally important traits are levels of cellular metabolites, such as cholesterol levels in humans or starch in food crops. Metabolic variation in yeast also holds practical importance with some Saccharomyces strains better suited to making ethanol for biofuel and others tailored to making flavorful wine. This metabolic heterogeneity can be used to gain insight into general principles of metabolic regulation which effect metabolite abundance in eukaryotes. To this end, we examined inter-strain differences in metabolism in over 100 closely related S. cerevisiae strains. We identified over 50 genetic loci that control the levels of specific metabolites, including not only loci that encode metabolic enzymes, but also those that encode global cellular regulators. For example, differences in the sequence of ira2, an inhibitor of Ras, lead to differences in central carbon metabolite levels, and polymorphisms in slt2, a poorly characterized MAP kinase, alter levels of sulfur-containing metabolites. These findings provide insights into the mechanisms cells use to control metabolite concentrations.


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