Genes encoding putative biogenic amine receptors in the parasitic nematode Brugia malayi.
Filarial nematodes, such as Brugia malayi, cause major health problems worldwide. The lack of a vaccine against B. malayi, combined with ineffective chemotherapy against the adult has prompted the examination of biogenic amine receptors (BARs) as possible targets for drug discovery. We employed bioinformatics to identify genes encoding putative B. malayi BARs. Surprisingly, the B. malayi genome contains half of the genes predicted to encode BARs in the genomes of free-living nematodes such as Caenorhabditis elegans or C. briggsae; however, all of the predicted B. malayi receptors have clear orthologues in C. elegans. The B. malayi genes encode each of the major BAR subclasses, including three serotonin, two dopamine and two tyramine/octopamine receptors and the structure of orthologous BAR genes is conserved. We find that potential G-protein coupling and ligand-specificity of individual BARs may be predicted by phylogenetic comparisons. Our results provide a framework for how G-protein coupled receptors may be targeted for drug development in medically important parasitic nematodes.
Smith
Katherine A
KA
Department of Biological Sciences, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA.
Komuniecki
Richard W
RW
Ghedin
Elodie
E
Spiro
David
D
Gray
John
J
D000595:Amino Acid Sequence; D000818:Animals; D001679:Biogenic Amines / Q000737:chemistry / Q000378:metabolism; D017178:Brugia malayi / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics; D015723:Gene Library; D017238:Genes, Helminth / Q000235:genetics*; D049751:Genome, Helminth / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D017982:Receptors, Biogenic Amine / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D001679:Biogenic Amines; D017982:Receptors, Biogenic Amine; D043562:Receptors, G-Protein-Coupled