Parathyroid hormone gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii)

• Published in: Journal of bone and mineral research Vol. 25; no. 12; pp. 2613 - 2623
• Main Authors: Liu, Yang, Ibrahim, Alexander S, Tay, Boon‐Hui, Richardson, Samantha J, Bell, Justin, Walker, Terence I, Brenner, Sydney, Venkatesh, Byrappa, Danks, Janine A
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2010; Wiley; Wiley Subscription Services, Inc
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Callorhinchus milii; Cyclic AMP - pharmacology; EVOLUTION; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation - drug effects; Genome - genetics; Humans; Immunohistochemistry; Marine; Molecular Sequence Data; Multigene Family - genetics; Organ Specificity - drug effects; Parathyroid Hormone - chemistry; Parathyroid Hormone - genetics; Parathyroid Hormone - metabolism; Phylogeny; PTH/PTHRP; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; SHARKS; Sharks - genetics; SKELETON; Skeleton and joints; Vertebrates: osteoarticular system, musculoskeletal system; Osteoarticular system; Vertebrata; Mammalia; EVOLUTION; Gene; Parathyroid hormone; Peptide hormone; SHARKS; Skeleton; PTH/PTHRP
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.178

The development of bone was a major step in the evolution of vertebrates. A bony skeleton provided structural support and a calcium reservoir essential for the movement from an aquatic to a terrestrial environment. Cartilaginous fishes are the oldest living group of jawed vertebrates. In this study we have identified three members of the parathyroid hormone (Pth) gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii). The three genes include two Pth genes, designated as Pth1 and Pth2, and a Pthrp gene. Phylogenetic analysis suggested that elephant shark Pth2 is an ancient gene whose orthologue is lost in bony vertebrates. The Pth1 and Pth2 genes have the same structure as the Pth gene in bony vertebrates, whereas the structure of the Pthrp gene is more complex in tetrapods compared with elephant shark. The three elephant shark genes showed distinct patterns of expression, with Pth2 being expressed only in the brain and spleen. This contrasts with localization of the corresponding proteins, which showed considerable overlap in their distribution. There were conserved sites of localization for Pthrp between elephant shark and mammals, including tissues such as kidney, skin, skeletal and cardiac muscle, pancreas, and cartilage. The elephant shark Pth1(1–34) and Pthrp(1–34) peptides were able to stimulate cAMP accumulation in mammalian UMR106.01 cells. However, Pth2(1–34) peptide did not show such PTH‐like biologic activity. The presence of Pth and Pthrp genes in the elephant shark indicates that these genes played fundamental roles before their recruitment to bone development in bony jawed vertebrates. © 2010 American Society for Bone and Mineral Research.