Evolutionary origins of the endocannabinoid system
Gene. 2006-03-01; 370: 64-74
DOI: 10.1016/j.gene.2005.11.004
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1. Gene. 2006 Mar 29;370:64-74. doi: 10.1016/j.gene.2005.11.004. Epub 2006 Jan
23.
Evolutionary origins of the endocannabinoid system.
McPartland JM(1), Matias I, Di Marzo V, Glass M.
Author information:
(1)GW Pharmaceuticals, 53 Washington Street Ext., Middlebury, VT 05753, USA.
Endocannabinoid system evolution was estimated by searching for functional
orthologs in the genomes of twelve phylogenetically diverse organisms: Homo
sapiens, Mus musculus, Takifugu rubripes, Ciona intestinalis, Caenorhabditis
elegans, Drosophila melanogaster, Saccharomyces cerevisiae, Arabidopsis
thaliana, Plasmodium falciparum, Tetrahymena thermophila, Archaeoglobus
fulgidus, and Mycobacterium tuberculosis. Sequences similar to human
endocannabinoid exon sequences were derived from filtered BLAST searches, and
subjected to phylogenetic testing with ClustalX and tree building programs.
Monophyletic clades that agreed with broader phylogenetic evidence (i.e., gene
trees displaying topographical congruence with species trees) were considered
orthologs. The capacity of orthologs to function as endocannabinoid proteins was
predicted with pattern profilers (Pfam, Prosite, TMHMM, and pSORT), and by
examining queried sequences for amino acid motifs known to serve critical roles
in endocannabinoid protein function (obtained from a database of site-directed
mutagenesis studies). This novel transfer of functional information onto gene
trees enabled us to better predict the functional origins of the endocannabinoid
system. Within this limited number of twelve organisms, the endocannabinoid
genes exhibited heterogeneous evolutionary trajectories, with functional
orthologs limited to mammals (TRPV1 and GPR55), or vertebrates (CB2 and
DAGLbeta), or chordates (MAGL and COX2), or animals (DAGLalpha and CB1-like
receptors), or opisthokonta (animals and fungi, NAPE-PLD), or eukaryotes (FAAH).
Our methods identified fewer orthologs than did automated annotation systems,
such as HomoloGene. Phylogenetic profiles, nonorthologous gene displacement,
functional convergence, and coevolution are discussed.
DOI: 10.1016/j.gene.2005.11.004
PMID: 16434153 [Indexed for MEDLINE]