Evidence for kinship between diverse G-protein coupled receptors

In an earlier publication we described similarities at the primary sequence level between the first probable plant G-protein coupled receptor (GPCR) a nd three GPCR families (families A, B and F according to Kolakowski's class ification) that were previously considered evolutionarily unrelated. Here w e analyze further the relatedness among different GPCR families. By using PSI-BLAST, which is a search algorithm that is more potent in dete cting weak similarities, one finds additional similarities between GPCR fam ilies that have not previously been described. Based on these comparisons, it is possible to divide all the GPCR families into one large clade and two smaller ones. The large clade includes the rhodopsin family (family A), th e glucagon receptor family (family B), cyclic AMP receptors (family F), an Arabidopsis thaliana receptor, the Frizzled family and probably also the ST E3 pheromone receptors (family E) and vomeronasal receptors type 1. The sma ller clades consist of, in one case, BOSS and the GABA-B family of receptor s (family C), and in the other the STE2 pheromone receptors (family D) alon e. Although our findings are likely to reflect a common ancestry within eac h of these clades, whether or not two or all three of the clades also share an even more ancient ancestor between them remains an open question that c annot be answered from our present data. (C) 1999 Elsevier Science B.V. All rights reserved.