The four aldehyde oxidases of Drosophila melanogaster have different gene expression patterns and enzyme substrate specificities

Zvonimir Marelja, Miriam Dambowsky, Marco Bolis, Marina L. Georgiou, Enrico Garattini, Fanis Missirlis, Silke Leimkühler

Research output: Contribution to journalArticlepeer-review

Abstract

In the genome of Drosophila melanogaster, four genes coding for aldehyde oxidases (AOX1-4) were identified on chromosome 3. Phylogenetic analysis showed that the AOX gene cluster evolved via independent duplication events in the vertebrate and invertebrate lineages. The functional role and the substrate specificity of the distinct Drosophila AOX enzymes is unknown. Two loss-of-function mutant alleles in this gene region, low pyridoxal oxidase (Po(lpo)) and aldehyde oxidase-1 (Aldox-1(n1)) are associated with a phenotype characterized by undetectable AOX enzymatic activity. However, the genes involved and the corresponding mutations have not yet been identified. In this study we characterized the activities, substrate specificities and expression profiles of the four AOX enzymes in D. melanogaster. We show that the Po(lpo)-associated phenotype is the consequence of a structural alteration of the AOX1 gene. We identified an 11-bp deletion in the Po(lpo) allele, resulting in a frame-shift event, which removes the molybdenum cofactor domain of the encoded enzyme. Furthermore, we show that AOX2 activity is detectable only during metamorphosis and characterize a Minos-AOX2 insertion in this developmental gene that disrupts its activity. We demonstrate that the Aldox-1(n1) phenotype maps to the AOX3 gene and AOX4 activity is not detectable in our assays.

Original languageEnglish
Pages (from-to)2201-2211
Number of pages11
JournalJournal of Experimental Biology
Volume217
DOIs
Publication statusPublished - Jun 15 2014

Keywords

  • Aldehyde oxidase
  • Drosophila melanogaster
  • Gene duplication
  • Molybdoenzymes
  • Substrate specificities

ASJC Scopus subject areas

  • Medicine(all)

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