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].