Nucleotide variations in the lxd region of Drosophila melanogaster: Characterization of a candidate modifier of lifespan

We have investigated the structure and function of several proteins that might influence adult lifespans in Drosophila melanogaster. The present report focuses on the gene lxd ('low xanthine dehydrogenase'), which lies in a region of chromosome III identified by QTL-mapping as potentially important for lifespan. DNA sequence of a 3780 bp genomic fragment containing the lxd locus reveals differences between long-lived and control inbred lines. In order to determine the importance of nucleotide replacements, the intron/exon boundaries have been determined, based on peptide alignment and conserved amino acids. We identified four exons in the lxd coding region. The deduced amino acid sequence of exon 4 shows 46.5% identity with Escherichia coli MoaC sequences. There are eight nucleotide substitutions in exons differentiating the inbred lines, three in exon 3 and five in exon 4. One of the exon 4 substitutions has resulted in a Thr-Ile replacement at the protein surface, but not entirely solvent exposed. This substitution is potentially a modifier of lifespan via oxygen defense, but since the activities of three molybdoenzymes are unaffected in inbred lines, this possibility seems remote.