Of the many thousands of genes encoding proteins of unknown function, the most enigmatic are the “silent” ones—those that exhibit no detectable phenotype when deleted from the genome. On page 45, Raamsdonk et al. show that, at least in yeast, gene function can be accurately predicted by examining the levels of various known metabolites. Using sophisticated statistical methods and NMR for comprehensive analysis of metabolite concentrations, the authors showed that, in principle, the function of silent genes can be revealed by comparing the metabolic profile of a yeast strain deleted for a silent gene to the profiles of deletion strains with known cellular roles.
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Sinclair, M. Silent genes find a voice. Nat Biotechnol 19, 8 (2001). https://doi.org/10.1038/83620