The GRAFS classification system of G-protein coupled receptors in comparative perspective.

The super-family of G-protein coupled receptors (GPCRs) is one of the largest groups of proteins in vertebrate species. The receptors are very diverse in structure and function but they still share some common structural elements. Our recent phylogenetic studies indicate that most human GPCRs can be grouped into five main families named; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin, forming the GRAFS classification system. The rhodopsin family is the largest and forms four main groups termed alpha, beta, gamma, and delta with 13 sub-branches. We have evidence that the main families of the GRAFS classification system arose prior to the split of nematodes from the lineage leading to chordates. The major part of all GPCRs in mammalian, fish, tunicate, insect, and nematode species belong to the GRAFS families. The evolution of GPCRs in different phylogenetic branches are, however, very variable as some of the branches are specific for certain lineages such as vertebrates or mammals, while others are found in a much larger variety of species. In this review, we provide an insight in several studies that are being performed to elucidate the evolutionary history of the GPCR family.