Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates.
Thyroid hormones modulate not only multiple functions in vertebrates (energy metabolism, central nervous system function, seasonal changes in physiology, and behavior) but also in some non-vertebrates where they control critical post-embryonic developmental transitions such as metamorphosis. Despite their obvious biological importance, the thyroid hormone precursor protein, thyroglobulin (Tg), has been experimentally investigated only in mammals. This may bias our view of how thyroid hormones are produced in other organisms. In this study we searched genomic databases and found Tg orthologs in all vertebrates including the sea lamprey (Petromyzon marinus). We cloned a full-size Tg coding sequence from western clawed frog (Xenopus tropicalis) and zebrafish (Danio rerio). Comparisons between the representative mammal, amphibian, teleost fish, and basal vertebrate indicate that all of the different domains of Tg, as well as Tg regional structure, are conserved throughout the vertebrates. Indeed, in Xenopus, zebrafish, and lamprey Tgs, key residues, including the hormonogenic tyrosines and the disulfide bond-forming cysteines critical for Tg function, are well conserved despite overall divergence of amino acid sequences. We uncovered upstream sequences that include start codons of zebrafish and Xenopus Tgs and experimentally proved that these are full-length secreted proteins, which are specifically recognized by antibodies against rat Tg. By contrast, we have not been able to find any orthologs of Tg among non-vertebrate species. Thus, Tg appears to be a novel protein elaborated as a single event at the base of vertebrates and virtually unchanged thereafter.
From the Institut de Génomique Fonctionnelle de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
Guillaume
G
Holzer
Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan 48109.
Yoshiaki
Y
Morishita
Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, CNRS UMR 7221, Muséum National d'Histoire Naturelle, 7 rue Cuvier 75231 Paris cedex 05, France, and.
Jean-Baptiste
JB
Fini
From the Institut de Génomique Fonctionnelle de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
Thibault
T
Lorin
From the Institut de Génomique Fonctionnelle de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
Benjamin
B
Gillet
From the Institut de Génomique Fonctionnelle de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
Sandrine
S
Hughes
From the Institut de Génomique Fonctionnelle de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
Marie
M
Tohmé
Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique, Université Claude Bernard Lyon 1, CNRS UMR 5086, Institut de Biologie et Chimie des Protéines, 7 passage du Vercors, 69367 Lyon cedex 07, France.
Gilbert
G
Deléage
Evolution des Régulations Endocriniennes, Département Régulations, Développement et Diversité Moléculaire, CNRS UMR 7221, Muséum National d'Histoire Naturelle, 7 rue Cuvier 75231 Paris cedex 05, France, and.
Barbara
B
Demeneix
Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan 48109, parvan@umich.edu.
Peter
P
Arvan
From the Institut de Génomique Fonctionnelle de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5242, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France, vincent.laudet@obs-banyuls.fr.
Vincent
V
Laudet
D000818:Animals; D019143:Evolution, Molecular; D007798:Lampreys / Q000235:genetics*; D051381:Rats; D013954:Thyroglobulin / Q000235:genetics*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D013954:Thyroglobulin
Xenopus; metamorphosis; molecular evolution; thyroglobulin; thyroid; thyroid hormone; zebrafish