Cloning of the bone Gla protein gene from the teleost fish Sparus aurata. Evidence for overall conservation in gene organization and bone-specific expression from fish to man.
Bone Gla protein (BGP, Osteocalcin) is a bone-specific vitamin K-dependent protein which has been intensively studied in mammals. Although BGP is the most abundant non-collagenous protein of bone, its mode of action at the molecular level remains unclear. From an evolutionary point of view, the appearance of BGP seems to parallel the appearance of hydroxyapatite-containing bone structures since it has never been found in elasmobranchs, whose skeleton is composed of calcified cartilage. Accordingly, recent work indicates that, in mammalian bone, BGP is required for adequate maturation of the hydroxyapatite crystal. Taken together, these data suggest that teleost fishes, presumably the first vertebrates to develop a BGP-containing skeleton, may be a useful model to further investigate BGP function. In addition, fish offer several advantages over mammalian models, due to a large progeny, external embryonic development and transparency of larvae. In the present work, the BGP cDNA and gene were cloned from a teleost fish, Sparus aurata, and its tissue distribution, pattern of developmental expression and evolutionary pathways analyzed. The molecular organization of the Sparus BGP (spBGP) gene is similar to mammalian BGP genes, and its expression throughout development follows the onset of calcification. The spBGP gene encodes a pre-propeptide of 97 amino acid residues, expressed only in bone and showing extensive homology to its mammalian homologs. Phylogenetic analysis of the available BGP sequences supports the hypothesis that all BGPs have a single origin and share a common ancestor with a related vitamin K-dependent protein (Matrix Gla protein).
Pinto
J P
JP
University of Algarve, Center for Marine Sciences, Campus de Gambelas, 8000-810, Faro, Portugal.
Ohresser
M C
MC
Cancela
M L
ML
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001842:Bone and Bones / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D007438:Introns; D008969:Molecular Sequence Data; D015675:Osteocalcin / Q000235:genetics*; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D021541:Sea Bream / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D018076:DNA, Complementary; D012333:RNA, Messenger; D015675:Osteocalcin