A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations

A large proportion of the 6,000 genes present in the genome of Saccharomyce s cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are "silent," that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are del eted from the genome. We demonstrate how the intracellular concentrations o f metabolites can reveal phenotypes for proteins active in metabolic regula tion. Quantification of the change of several metabolite concentrations rel ative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same wa y, comprehensive analyses of metabolite concentrations in mutants, providin g "metabolic snapshots," can reveal functions when snapshots from strains d eleted for unstudied genes are compared to those deleted for known genes. T his approach to functional analysis, using comparative metabolomics, we cal l FANCY-an abbreviation for functional analysis by co-responses in yeast.