A putative Drosophila homolog of the Huntington's disease gene

The Huntington's disease (HD) gene encodes a protein, huntingtin, with no k nown function and no detectable sequence similarity to other proteins in cu rrent databases. To gain insight into the normal biological role of hunting tin, we isolated and sequenced a cDNA encoding a protein that is a likely h omolog of the HD gene product in Drosophila melanogaster, We also determine d the complete sequence of 43 125 contiguous base pairs of genomic DNA that encompass the Drosophila HD gene, allowing the intron-exon structure and 5 '- and 3'-flanking regions to be delineated, The predicted Drosophila hunti ngtin protein has 3583 amino acids, which is several hundred amino acids la rger than any other previously characterized member of the HD family. Analy sis of the genomic and cDNA sequences indicates that Drosophila HD has 29 e xons, compared with the 67 exons present in vertebrate HD genes, and that D rosophila huntingtin lacks the polyglutamine and polyproline stretches pres ent in its mammalian counterparts. The Drosophila HD mRNA is expressed in a broad range of developmental stages and in the adult, a temporal pattern o f expression similar to that observed for mammalian HD transcripts. We can discern five regions of high similarity from multiple sequence alignments b etween Drosophila and vertebrate huntingtins, These regions may define func tionally important domains within the protein.