EVOLUTION OF TRANSTHYRETIN IN MARSUPIALS

The evolution of the expression and the structure of the gene for tran sthyretin, a thyroxine-binding plasma protein formerly called prealbum in, was studied in three marsupial species: the South American polypro todont Monodelphis domestica, the Australian polyprotodont Sminthopsis macroura and the Australian diprotodont Petaurus breviceps. The trans thyretin gene was found to be expressed in the choroid plexus of all t hree species. In liver it was expressed in P. breviceps and in M. dome stica, but not in S. macroura. This, together with previous studies [R ichardson, S. J., Bradley, A. J., Duan, W., Wettenhall, R. E. H., Harm s, P. J., Babon, J. J., Southwell, B. R., Nicol, S., Donnellan, S. C. & Schreiber, G. (1994) Am. J. Physiol. 266, R1359-R1370], suggests the independent evolution of transthyretin synthesis in the liver of the American Polyprotodonta and the Australian Diprotodonta. The results o btained from cloning and sequencing of the cDNA for transthyretin from the three species suggested that, in the evolution of the structure o f transthyretin in vertebrates, marsupial transthyretin structures are intermediate between bird/reptile and eutherian transthyretin structu res. In marsupials, as in birds and reptiles, a hydrophobic tripeptide beginning with valine and ending with histidine was found in transthy retin at a position which has been identified in eutherians as the bor der between exon 1 and intron 1. In humans, rats and mice, the nine nu cleotides, coding for this tripeptide in marsupials/reptiles/birds, ar e found at the 5' end of intron 1. They are no longer present in matur e transthyretin mRNA. This results in a change in character of the N-t ermini of the subunits of transthyretin from hydrophobic to hydrophili c. This change might affect the accessibility of the thyroxine-binding site in the central channel of transthyretin, since, at least in huma ns, the N-termini of the subunits of transthyretin are located in the vicinity of the channel entrance [Hamilton, J. A., Steinrauf, L. K., B raden, B. C., Liepnieks, J., Benson, M. D., Holmgren, G., Sandgren, O. & Steen, L. (1993) J. Biol. Chem. 268, 2416-2424].