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Genetic Basis of Metabolome Variation in Yeast

Author(s): Breunig, Jeffrey S.; Hackett, Sean R.; Rabinowitz, Joshua D.; Kruglyak, Leonid

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Abstract: Metabolism, the conversion of nutrients into usable energy and biochemical building blocks, is an essential feature of all cells. The genetic factors responsible for inter-individual metabolic variability remain poorly understood. To investigate genetic causes of metabolome variation, we measured the concentrations of 74 metabolites across 100 segregants from a Saccharomyces cerevisiae cross by liquid chromatography-tandem mass spectrometry. We found 52 quantitative trait loci for 34 metabolites. These included linkages due to overt changes in metabolic genes, e.g., linking pyrimidine intermediates to the deletion of ura3. They also included linkages not directly related to metabolic enzymes, such as those for five central carbon metabolites to ira2, a Ras/PKA pathway regulator, and for the metabolites, S-adenosyl-methionine and S-adenosyl-homocysteine to slt2, a MAP kinase involved in cell wall integrity. The variant of ira2 that elevates metabolite levels also increases glucose uptake and ethanol secretion. These results highlight specific examples of genetic variability, including in genes without prior known metabolic regulatory function, that impact yeast metabolism.
Publication Date: 6-Mar-2014
Electronic Publication Date: 6-Mar-2014
Citation: Breunig, Jeffrey S, Hackett, Sean R, Rabinowitz, Joshua D, Kruglyak, Leonid. (2014). Genetic Basis of Metabolome Variation in Yeast. PLoS Genetics, 10 (3), e1004142 - e1004142. doi:10.1371/journal.pgen.1004142
DOI: doi:10.1371/journal.pgen.1004142
EISSN: 1553-7404
Pages: e1004142-1 - e1004142-15
Type of Material: Journal Article
Journal/Proceeding Title: PLoS Genetics
Version: Final published version. This is an open access article.

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