Molecular and functional evolution of the adrenomedullin family in vertebrates: What do fish studies tell us?

Adrenomedullin (AM) comprises a unique family of five paralogous peptides (AM1, 2, 3, 4 and 5) in teleost fish, of which AM1 is an ortholog of mammalian AM, and AM1/4 and AM2/3 were produced at the teleost-specific whole genome duplication. Therefore, CGRP, amylin, AM1, AM2 and AM5 existed when ray-finned fish and lobe-finned fish (leading to tetrapods) were diverged. Based on this finding, we discovered novel AM2 and AM5 in mammals. In addition, comparative genomic analyses based on fish studies delineated an evolutionary history of the CGRP family of peptides in vertebrates. As a first chapter of this volume, we initially propose an idea of how the CGRP family, including multiple AM peptides, have been organized during the course of vertebrate evolution. We will also show how comparative fish studies can contribute to general and clinical endocrinology by providing new insights into the molecule and function of the CGRP family throughout vertebrate species.