Implications of gen(om)e duplications on the expansion and evolution of the GPCR signalling pathway

Abstract

Gene and genome duplications are important evolutionary events associated with the emergence of gene families and novel biological functions. G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins, and their associated signalling pathways control crucial physiological functions such as neurotransmission, endocrine activity, and immunity. However, the duplication history of the entire pathway across evolutionary time is unknown. Here, we performed a comprehensive analysis of the duplication events of the main interactors of the GPCR signalling cascade. We show that different components of the pathway evolved under distinct frequencies of duplication events, with G proteins and GPCRs exhibiting higher frequencies than the downstream mediators and regulators. We also found that GPCRs are evolutionarily younger than G proteins and that most receptors evolved before their ligands. Additionally, the GPCR signalling system experienced significant gene expansion through duplication during the emergence of placental mammals, which played an important role in all human body systems, particularly concerning ligands and G proteins. These results indicate that the expansion and diversification of the GPCR signalling pathway was based on independent and discrete duplication events of its main components, suggesting that the maintenance of duplicate genes within the pathway may have been mediated by the selection of complementary duplication and divergence processes between the signalling components at specific evolutionary stages.