Modulating Vertebrate Physiology by Genomic Fine-Tuning of GPCR Functions

G protein-coupled receptors (GPCRs) play a crucial role as membrane receptors, facilitating the communication of eukaryotic species with their environment and regulating cellular and organ interactions. Consequently, GPCRs hold immense potential in contributing to adaptation to ecological niches and responding to environmental shifts. Comparative analyses of vertebrate genomes reveal patterns of GPCR gene loss, expansion, and signatures of selection. Integrating this genomic data with insights from functional analyses of gene variants enables the interpretation of genotype-phenotype correlations. This review underscores the involvement of GPCRs in adaptive processes, presenting numerous examples of how alterations in GPCR functionality influence vertebrate physiology, or conversely, how environmental changes impact GPCR functions. The findings demonstrate that modifications in GPCR function contribute to adapting to aquatic, arid, and nocturnal habitats, influencing camouflage strategies, and specializing in particular dietary preferences. Furthermore, the adaptability of GPCR functions provides an effective mechanism in facilitating past, recent, or ongoing adaptations in animal domestication and human evolution and should be considered in therapeutic strategies and drug development.