Authors

P McVeighP McCusker²; N J Marks²; A Mousley²; R M Morphew¹; P M Brophy¹; S Paterson³; J E Hodgkinson³; A G Maule²;  ¹ Aberystwyth University;  ² Queen's University Belfast;  ³ University of Liverpool

Discussion

As targets for a large proportion of licensed human pharmaceuticals, G protein coupled receptors (GPCRs) could be key targets for the development of new anthelmintics. Using hidden Markov model (HMM)-driven computational methods, we have identified 148 high confidence GPCRs from the Fasciola hepatica genome comprising glutamate, rhodopsin, adhesion, frizzled and smoothened receptor families; we did not identify any secretin-like receptors. Pairwise comparisons using a sequence-clustering algorithm (CLANS) compared fluke GPCRs with those of flatworms and non-flatworm phyla. Amongst rhodopsins, this approach identified many evolutionarily conserved amine and peptide receptors, and also verified the presence of the previously described PROF1 (Platyhelminth Rhodopsin Orphan Family #1) family, containing GPCRs that appear uniquely expanded in the platyhelminth lineage. Our data describe up to an additional seven such groupings (PROF2-PROF8) in F. hepatica and other trematodes, suggesting considerable expansion of GPCR diversity within phylum Platyhelminthes. This work provides the first GPCR profile from F. hepatica, and the first description of several classes of trematode-specific GPCRs, and will facilitate the first functional genomic explorations of these important potential anthelmintic targets