Expression and functional profiling reveal distinct gene classes involved in fatty acid metabolism

Cells respond to fatty acid exposure by metabolic reorganization and proliferation of peroxisomes. Described here is the development and application of a genome-wide screen to identify nonessential yeast genes necessary for efficient metabolism of myristic and oleic acids. Comparison of the resultant fitness data set with an integrated data set of genes transcriptionally responsive to fatty acids revealed very little overlap between the data sets. Furthermore, the fitness data set enriched for genes involved in peroxisome biogenesis and other processes related to cell morphology, whereas the expression data set enriched for genes related to metabolism. These data suggest that in response to fatty acid exposure, transcriptional control is biased towards metabolic reorganization, and structural changes tend to be controlled post-transcriptionally. They also suggest that fatty acid responsive metabolic networks are more robust than those related to cell structure. Statistical analyses of these and other global data sets suggest that the utilization of distinct control mechanisms for the execution of morphological versus metabolic responses is widespread.