Examining the Dynamic Evolution of G Protein-Coupled Receptors

The valuable source of large-scale genomic information initiated attempts to identify the origin(s) of G protein-coupled receptors (GPCR), count and categorize those genes, and follow their evolutionary history. Being present in fungi, plants, and unicellular eukaryotes, GPCR must have evolved before the plant-fungianimal split about 1.5 billion years ago. Phylogenetic analyses revealed several kinds of evolutionary patterns that occurred during GPCR evolution including one-to-one orthologous relationships, speciesspecifi c gene expansion, and episodic duplication of the entire GPCR repertoire in certain species lineages. These data document the highly dynamic process of birth and death of GPCR genes since hundreds of millions of years. Genetic drift and selective forces have shaped the individual structure of a given receptor gene but also of the species-specifi c receptor repertoire – a process that is still ongoing. These processes have left footprints in the genomic sequence that can be detected by bioinformatic methods and may help to interpret receptor function in the light of a given species in its environment. Reasonable intraspecies sequence variability in GPCR is either physiologically tolerated or promotes individual phenotypes and adaptation, but also susceptibilities for diseases. Therefore, the impact of GPCR variants in epistatic networks will be an important task of future GPCR research. The chapter summarizes evolutionary processes working on GPCR genes and sheds light on their consequences at the levels of receptor structure and function.