The adhesion G-protein-coupled receptors (GPCRs) (also termed LN-7TM or EGF-7TM receptors) are membrane-bound
proteins with long N-termini which contain multiple domains. Little is known about this subfamily of GPCRs which is believed
to bind different proteins that promote cell-to-cell and cell-to-matrix interactions with its long N-termini. Many of the human
and mouse adhesion GPCRs were recently assembled from EST-data. Here, a high-throughput method for finding adhesion
GPCR orthologs in evolutionary diverse species is presented in order to understand more of the evolution behind this
protein family. Species orthologs were identified in Gallus gallus (chicken), Caenorhabditis elegans (nematode), Drosophila melanogaster (fruit fly) and Takifugu rubripes (fugu) by BLAT searches at UCSC and by profile Hidden Markov Model (HMM) searches of public available genome data bases. The complex repertoire of conserved domains in the N-termini was identified by RPS-BLAST and HMM searches. The exons in the seven transmembrane regions (TM) were manually assembled for the newly discovered orthologs. Phylogenetic analyses of the TM-regions were performed by Neighborjoining, TREE-PUZZLE, and Maximum parsimony algorithms. In G.gallus, C.elegans, D.melanogaster, and T.rubripes, 22, 5, 3, and 24 adhesion GPCRs were identified respectively. The phylogenetic analysis reveals that the newly discovered sequences together with known human adhesion GPCR sequences cluster into nine groups. A majority of the G.gallus and T.rubripes sequences are obvious orthologs to known human adhesion GPCRs. They also share the same repertoire of conserved domains in the N-termini, indicating that these GPCRs have similar function in those two species. This is the first report showing that there exist adhesion GPCRs in C. elegans and D. melanogaster, and this fact is strong evidence that the adhesion GPCR family is at least 700 million years old. |