Figure 2.

Schematic evolution of CRF and related peptides and receptors. The progenitor peptide for CRF and antidiuretic hormone had evolved before separation of chordates because CRF analogs were not found in tunicates or protostomates. The novel function CRF/DH (diuretic hormone)-like peptides in multicellular organisms required development of specific receptors, and those receptors once appeared evolved with peptides and were subjected to genome duplications (64). In the case of CRF precursor, the duplication occurred twice, whereas for CRFR it occurred only once. UCN, urocortin.