There are many genes with homology to human ADH in the C. elegans genome, and ADH activity has been directly demonstrated in worms using a spectrophotometric assay (Williamson et al., 1991). Our goal was to examine the behavioral consequences of impairing alcohol metabolism, and therefore we chose a subset of the genes with strong homology to human liver ADHs as good candidates for subsequent analysis. We used two methods to identify potential ADHs that metabolize ethanol in the worm. First, we identified sodh-1, a gene that showed transcriptional regulation in response to a prolonged treatment with very high concentrations (7%) of ethanol (Kwon et al., 2004) and has been annotated as an ADH. We also tested the two genes with highest homology to sodh-1: sodh-2 and D2063.1. Second, we used the primary amino acid sequence of human liver ADH (Human liver ADH proteins, ADH1A (Accession: NP_000658.1), ADH1B (Accession: NP_000659.2), and ADH1C (Accession: NP_000660.1)) in BLAST searches to identify the C. elegans protein with the highest homology, H24K24.3. Although previous work had identified transcripts from both sodh-1 and H24K24.3 as being expressed from ADH-encoding genes, these genes have not previously been functionally characterized (Glasner et al., 1995; Waterston et al., 1992).
