Molecular evolution of glutamate receptors: A primitive signaling mechanism that existed before plants and animals diverged

We performed a genealogical analysis of the ionotropic glutamate receptor ( iGluR) gene family, which includes the animal iGluRs and the newly isolated glutamate receptor-like genes (GLR) of plants discovered in Arabidopsis. D istance measures firmly placed the plant GLR genes within the iGluR clade a s opposed to other ion channel clades and indicated that iGluRs may be a pr imitive signaling mechanism that predated the divergence of animals and pla nts. Moreover, phylogenetic analyses using both parsimony and neighbor join ing indicated that the divergence of animal iGluRs and plant GLR genes pred ated the divergence of iGluR subtypes (NMDA vs. AMPA/KA) in animals. By est imating the congruence of the various glutamate receptor gene regions, we s howed that the different functional domains, including the two ligand-bindi ng domains and the transmembrane regions, have coevolved, suggesting that t hey assembled together before plants and animals diverged. Based on residue conservation and divergence as well as positions of residues with respect to functional domains of iGluR proteins, we attempted to examine structure- function relationships. This analysis defined M3 as the most highly conserv ed transmembrane domain and identified potential functionally important con served residues whose function can be examined in future studies.