New insights into the evolution of the relaxin - LGR signaling system

Recent studies have characterized two orphan G-protein-coupled receptors, LGR7 and LGR8, as relaxin receptors. Although these studies have revealed the signaling mechanisms of relaxin and related peptides, the finding that there are more relaxin family peptides than there are coevolved receptors has confounded our understanding of the physiological role of LGR signaling. Phylogenetic analysis of LGRs and coevolved relaxin family peptides from different metazoans suggests that, whereas the number of relaxin receptors remained constant during vertebrate evolution, the ancestor gene for relaxin duplicated multiple times in a vertebrate branch-specific manner. Therefore, relaxin family peptides from different branches of vertebrates might have adapted to distinct physiological roles via a limited number of genes encoding receptors. Illustration of the evolution of this unique group of signaling molecules provides an opportunity to reveal not only the physiological processes regulated by relaxin family peptides that have been characterized biochemically, but also the signaling of orphan ligands in the relaxin family of genes.