The evolution of transthyretin synthesis in vertebrate liver, in primitive eukaryotes and in bacteria.
Thyroid hormones are evolutionarily old signal molecules, which can partition between compartments by partitioning into lipid membranes. The role of thyroid hormone distributor proteins is to ensure that sufficient thyroid hormone remains in the bloodstream. Of particular interest is the role of transthyretin, synthesised by the liver and secreted into the blood. In this review, three hypotheses are presented, suggesting the selection pressures leading to the onset of transthyretin synthesis in the liver during evolution. A thyroid hormone distribution network would be a selection advantage over a single protein performing this function. Similarly to the situation in eutherians, hepatic transthyretin synthesis in marsupials is under negative acute phase regulation. The overall three-dimensional structure of transthyretin did not change appreciably during vertebrate evolution. The region of the primary sequence which evolved most was the N-terminal region of the subunit. The N-termini of transthyretin changed from longer and more hydrophobic in reptiles/birds, to shorter and more hydrophilic in eutherians. These changes are correlated with a change in preference from binding of triiodothyronine, to binding thyroxine. As the rest of the molecule had not changed significantly during vertebrate evolution, the gene coding for transthyretin must have evolved prior to the divergence of the vertebrates from the non-vertebrates. Five open reading frames in the genomes of C. elegans (2), S. dublin, S. pombe and E. coli were identified. The protein products are predicted to form tetramers similar to transthyretins. Two possible functions of these proteins are suggested.
Richardson
Samantha J
SJ
Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia. sjrich@unimelb.edu.au
D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D008099:Liver / Q000378:metabolism*; D010802:Phylogeny; D011228:Prealbumin / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D014714:Vertebrates / Q000378:metabolism*
D011228:Prealbumin