title: Genetic basis of metabolome variation in yeast.
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.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America; Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Breunig
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America; Graduate Program in Quantitative and Computational Biology, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Hackett
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America; Department of Chemistry, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.affiliation: Departments of Human Genetics and Biological Chemistry, David Geffen School of Medicine, UCLA, Los Angeles, California, United States of America; Howard Hughes Medical Institute, UCLA, Los Angeles, California, United States of America.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kruglyak
mesh_terms: D050260:Carbohydrate Metabolism / Q000235:genetics; D002853:Chromatography, Liquid; D008040:Genetic Linkage; D055442:Metabolome / Q000235:genetics*; D055432:Metabolomics; D040641:Quantitative Trait Loci / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry