Lokits, A. D.,Indrischek, H.,Meiler, J.,Hamm, H. E.,Stadler, P. F.

G protein Coupled Receptors (GPCRs) are a highly studied class of receptors due to their integral role in cellular signaling and therefore as therapeutic targets. Their evolution has shaped the chemical and biomolecular signaling systems of eukaryotes [1, 2]. Within this signaling cascade, a transducing element, the heterotrimeric G protein, composed of a monomeric α and obligate βγ dimer, acts as an intracellular relay for activated GPCRs to convert their message into an amplified signaling cascade. With only 16 paralogs in humans, compared to the 800 GPCR genes, the evolution of heterotrimeric G protein α subunit has received less attention than their transmembrane protein partners. Shortly after their initial discovery and sequencing in several Mammalia species, the Gα subunit was found to be a highly conserved housekeeping protein [3]. As such, traces of genes encoding heterotrimeric G protein α subunits (GNA-) have been found in almost all major branches of Eukaryota [1, 4, 5] despite the proposed differences in GPCR and transmembrane receptor signaling mechanisms between the Unikonta and Bikonta lineages (see [1]). Using only Mammalia sequences, the first theory of G protein α evolution posited the relative evolution of four of the five Gα families (Gαi, Gαq, Gαs and Gα12; Gαv having not yet been discovered) [3]. Focusing on the development and radiation of the visual system, others have evaluated the evolution of transducins (GNAT1 and GNAT2) and other critical protein-coding genes in the vision signal transduction pathway in both rods and cones across Vertebrata and non-vertebrate Chordata [6, 7, 8, 9]. However, to our knowledge, there have been no reports focused on studying the evolution of the other three families of Gα in Deuterostomia with the exception of Gα subunits in the fish chemosensory systems [10], and a more recent, coarse-grained study evaluating paralog counts across Opisthokonta phylogeny [5].