The Adhesion family is unique among the GPCR (G protein-coupled receptor) families because of several features including long N-termini with multiple domains. The gene repertoire has recently been mined in great detail in several species including mouse, rat, dog, chicken and the early vertebrate Branchiostoma (Branchiostoma floridae) and one of the most primitive animals, the cniderian Nematostella (Nematostella vectensis). There is a one-to-one relationship of the rodent (mouse and rat) and human orthologues with the exception the EMR2 and EMR3 that do not seem to have orthologues in either rat or mouse. All 33 human Adhesion GPCR genes are present in the dog genome but the dog genome also contains 5 additional full-length Adhesion genes. The dog and human Adhesion orthologues have higher average protein sequence identity than the rodent (rat and mouse) and the human sequences. The Adhesion family is well-represented in chicken with 21 one-to-one orthologous with humans, while 12 human Adhesion GPCRs lack a chicken ortholog. Branchiostoma has rich repertoire of Adhesion GPCRs with at least 37 genes. Moreover, the Adhesion GPCRs in Branchiostoma have several novel domains their N-termini, like Somatomedin B, Kringle, Lectin C-type, SRCR, LDLa, Immunoglobulin I-set, CUB and TNFR. Nematostella has also Adhesion GPCRs that are show domain structure and sequence similarities in the transmembrane regions with different classes of mammalian GPCRs. The Nematostella genome has a unique set of Adhesion-like sequences lacking GPS domains. There is considerable evidence showing that the Adhesion family is ancestral to the peptide hormone binding Secretin family of GPCRs.