The
calcitonin (CT)/CT gene-related
peptides (
CGRPs) constitute a large
peptide family in vertebrates. However, no CT/
CGRP superfamily members have so far been identified in invertebrates, and the evolutionary process leading to the diverse vertebrate CT/
CGRP superfamily members remains unclear. In this study, we have identified an authentic invertebrate CT, Ci-CT, in the ascidian Ciona intestinalis, which is the
phylogenetically closest invertebrate chordate to vertebrates. The
amino acid sequence of Ci-CT was shown to display high similarity to those of vertebrate CTs and to share CT consensus motifs, including the
N-terminal circular region and
C-terminal amidated
proline. Furthermore, the Ci-CT gene was found to be the only Ciona CT/
CGRP superfamily gene. Ci-CT also exhibited less potent, but significant,
activation of the human CT receptor, as compared with salmon CT. Physiological analysis revealed that Ci-CT reduced the osteoclastic activity that is specific to vertebrate CTs. CD analysis demonstrated that Ci-CT weakly forms an
alpha-helix structure. These results provide evidence that the CT/
CGRP superfamily is essentially conserved in ascidians as well as in vertebrates, and indicate that Ci-CT is a prototype of vertebrate CT/
CGRP superfamily members. Moreover, expression analysis demonstrated that Ci-CT is expressed in more
organs than vertebrate CTs in the cognate
organs, suggesting that an original CT/
CGRP superfamily member gene was also expressed in multiple
organs, and each CT/
CGRP superfamily member
acquired its current specific tissue distribution and physiological role
concomitantly with diversification of the CT/
CGRP superfamily during the evolution of chordates. This is the first report on a CT/
CGRP superfamily member in invertebrates.
