Analysis of the Seven-Member AAD Gene Set Demonstrates That Genetic Redundancy in Yeast May Be More Apparent Than Real

Saccharomyces cerevisiae has seven genes encoding proteins with a high degree (>85%) of amino-acid sequence identity to the aryl-alcohol dehydrogenase of the lignin-degrading, filamentous fungus, Phanerochaete chrysosporium. All but one member of this gene set are telomere associated. Moreover, all contain a sequence similar to the DNA-binding site of the Yap1p transcriptional activator either upstream of or within their coding sequences. The expression of the AAD genes was found to be induced by chemicals, such as diamide and diethyl maleic acid ester (DEME), that cause an oxidative shock by inactivating the glutathione (GSH) reservoir of the cells. In contrast, the oxidizing agent hydrogen peroxide has no effect on the expression of these genes. We found that the response to anti-GSH agents was Yap1p dependent. The very high level of nucleotide sequence similarity between the AAD genes makes it difficult to determine if they are all involved in the oxidative-stress response. The use of single and multiple aad deletants demonstrated that only AAD4 (YDL243c) and AAD6 (YFL056/57c) respond to the oxidative stress. Of these two genes, only AAD4 is likely to be functional since the YFL056/57c open reading frame is interrupted by a stop codon. Thus, in terms of the function in response to oxidative stress, the sevenfold redundancy of the AAD gene set is more apparent than real.