Alpha/beta hydrolase2, a predicated gene adjacent to mad in Drosophila melanogaster, belongs to a new global multigene family and is associated with obesity

J Mol Evol. 2003 Mar;56(3):351-61. doi: 10.1007/s00239-002-2411-4.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromosome Walking
  • DNA, Complementary
  • DNA-Binding Proteins / genetics*
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / genetics*
  • Hydrolases / genetics*
  • Molecular Sequence Data
  • Multigene Family*
  • Obesity / genetics
  • Phylogeny
  • Transcription Factors / genetics*

Substances

  • DNA, Complementary
  • DNA-Binding Proteins
  • Drosophila Proteins
  • MAD protein, Drosophila
  • Transcription Factors
  • Hydrolases