title: The remarkable conservation of corticotropin-releasing hormone (CRH)-binding protein in the honeybee (Apis mellifera) dates the CRH system to a common ancestor of insects and vertebrates.
abstract: CRH-binding protein (CRH-BP) is a key factor in the regulation of CRH signaling; it modulates the bioactivity and bioavailability of CRH and its related peptides. The conservation of CRH-BP throughout vertebrates was only recently demonstrated. Here we report the presence of CRH-BP in the honeybee (Apis mellifera) and other insects. Honeybee CRH-BP resembles previously characterized vertebrate CRH-BP sequences with respect to conserved cysteine residues, gene organization, and overall sequence identity. Phylogenetic analyses confirm the unambiguous orthology of insect and vertebrate CRH-BP sequences. Soon after their discovery, it was noted that insect diuretic hormone-I (DH-I) and its receptor share similarities with the vertebrate CRH family and their receptors. Despite these similarities, demonstration of common ancestry of DH-I and the vertebrate CRH family is still speculative: the mature neuropeptides are short, and their genes differ substantially with regard to the number of coding exons. Moreover, DH and CRH receptors belong to the much larger family of G protein-coupled receptors. In contrast, the unique and conspicuous features of CRH-BP greatly facilitate the establishment of orthology over much larger evolutionary distances. The identification of CRH-BP in insects clearly indicates that this gene predates vertebrates by at least several hundred million years. Moreover, our findings imply that a CRH system is shared by insects and vertebrates alike and, consequently, that it has been present at least since the common ancestor to both phylogenetic lines of proto- and deuterostomians.
authors.affiliation: Department of Animal Physiology, Institute for Neuroscience, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Huising
authors.forename: Gert
authors.initials: G
authors.lastname: Flik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001516:Bees / Q000737:chemistry* / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004247:DNA / Q000032:analysis / Q000737:chemistry; D019143:Evolution, Molecular; D015870:Gene Expression; D006801:Humans; D007313:Insecta; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D014714:Vertebrates
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; C067133:corticotropin releasing factor-binding protein; D004247:DNA