title: Alpha/beta hydrolase2, a predicated gene adjacent to mad in Drosophila melanogaster, belongs to a new global multigene family and is associated with obesity.
abstract: The experimental validation of genes predicted from genomic sequence and the identification of functions for these genes is an increasingly important task. We report a multidisciplinary analysis of CG3488, a predicted gene adjacent to Mothers against dpp in Drosophila melanogaster. We cloned and sequenced a cDNA corresponding to CG3488 and we show that it is expressed in embryos. A computational analysis shows that CG3488 contains a number of conserved domains present in enzymes capable of lipid hydrolysis. A phylogenetic analysis shows that CG3488 is the homolog of human alpha/beta hydrolase2 and that these genes belong to a novel multigene family with members in animals, plants, fungi, and bacteria. A genetic analysis shows that heterozygosity for a chromosomal deletion that removes CG3488 dominantly enhances the excess lipid phenotype associated with a mutation in adipose, an uncloned obesity gene. Further, overexpression of a CG3488 transgene rescues this obesity phenotype. Overall, the data suggests that CG3488 functions as a lipase and that analyses of its homologs will provide unique insights into lipid metabolism in many species.
authors.affiliation: Deltagen, Incorporated, Menlo Park, CA 94025, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Wisotzkey
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Johnson
authors.forename: Norma T
authors.initials: NT
authors.lastname: Takaesu
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Newfeld
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016386:Chromosome Walking; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D006867:Hydrolases / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009765:Obesity / Q000235:genetics; D010802:Phylogeny; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; D014157:Transcription Factors; D006867:Hydrolases