G-protein couple receptor (GPCR) is one of the most striking examples of signalling proteins and it is only observed in eukaryotes. Based on various GPCR identification methods and classification systems, several evolutionary presumptions of different GPCR families have been reported. However, the prototype of GPCR still limits our knowledge. By investigating its structure and domain variance, the authors propose that GPCR might be evolved from prokaryotic world. The results given by the authors indicate that metabotropic glutamate receptor family would be the ancestor of GPCR. Phylogenetic analysis hints that one of metabotropic glutamate receptor GABA is possibly formed and evolved from the ancient chemical union of bacteriorhodopsin and periplasmic binding protein. The results obtained by the authors also unprecedentedly demonstrate that specific domains and identical structures are shown in each type of GPCR, which provides unique opportunities for future strategies on GPCR orphans' prediction and classification.