Perspectives in Biology and Medicine

THYROXINE'S EVOLUTIONARY ROOTS LELAND G. JOHNSON* Thyroxine and other thyroid hormones, which are familiar as metabolic regulators in homeothermic vertebrates and triggers of amphibian metamorphosis , are unique among vertebrate hormones in that they are amino acid derivatives that contain iodine, an element scarce in the environments of many vertebrates. This strong dependence on a sometimes vanishingly scarce resource seems curious and raises interesting questions about the evolutionary origin of these iodine-containing hormones [I]. What were the evolutionary roots ofthis iodine dependency? One answer is that ancestors of the chordates, the phylum to which vertebrate animals including ourselves belong, evolved in the ocean where iodine was fairly readily available . By the time fresh water and, eventually, terrestrial vertebrates evolved, it may have been too late to give up iodine dependency because iodinated molecules were too fundamentally important in the biology of the organisms [I]. While this assessment seems reasonable, it doesn't address the issue of how the iodine dependency originated. Where should we seek further clues about evolutionary origins of thyroid hormones and their regulatory roles? It seems useful to turn at the outset to results of comparative studies of thyroid hormones' functions. Metabolic effects of thyroid hormones are quite familiar to us because of their wellrecognized importance in human medicine and in the veterinary medicine of domesticated mammals and birds. But metabolic stimulation does not appear to be the oldest or most basic of thyroid hormone functions. Thyroid hormones affect growth, differentiation, and maturation of numerous tissues not only in mammals and birds, but in other vertebrates as well. The wider taxonomic distribution of these latter roles suggests that they are more ancient in an evolutionary sense [2, 3]. Thyroid hormone effects on metabolism apparently arose later in evolution during the emergence of Support received from the Australian Great Barrier Reef Marine Park Authority through the Crown-of-thorns Starfish Research Committee, the Australian Institute of Marine Science and file Augustana Research and Artist Fund is gratefully acknowledged. * Biology Department, Augustana College, Sioux Falls, SD 57197.© 1997 by The University of Chicago. All rights reserved. 0031-5982/97/4003-1017$1.00 Perspectives in Biology and Medicine, 40, 4 ¦ Summer 1997 529 homeothermy [1, 4], Thus, thyroid hormones might well be added to the list of evolutionary examples of already existing regulatory mechanisms being "plugged into" new control functions. General growth effects can be somewhat difficult to sort out because thyroid hormones so often act in concert with several other hormones that simultaneously affect growth [5] . But clearly, thyroid hormones promote differentiation and maturation of numerous tissues in various vertebrates [2, 3]. A good case could be made that the search for thyroid hormones' evolutionary roots would be advanced first by comparative study of the occurrence of iodine-containing amino acid derivatives in invertebrate animals and second by examination of possible roles the molecules play in regulating differentiation and maturation of invertebrates. With the use of radioactive iodine, it has been possible to test the ability of many invertebrates to accumulate iodine and incorporate it into organic molecules, especially amino acids, amino acid derivatives, and proteins. Except for echinoderms (interestingly from our perspective), some adult members of virtually all of the larger phyla of invertebrates have been shown to iodinate amino acids to some extent, and iodoproteins occur as structural molecules in hard tissues of several marine invertebrates. Some species ofmollusks even produce considerable quantities of thyroxine. This clearly suggests that iodination of amino acid derivatives and the production of thyroxine itself preceded the thyroid gland in evolution [6, 7] . But what evidence is there that iodine-containing molecules regulate development in invertebrates? Thyroxine accelerates metamorphosis in an ascidian, which is an invertebrate that shares membership in the Phylum Chordata with us and other vertebrate animals, but awide range ofsubstances can trigger metamorphosis in ascidians, just as is the case in larvae of other marine animals once they have developed to the point of competence for metamorphosis [8H ]. Other evidence of developmental effects of thyroxine in invertebrates had for some time essentially been limited to Spangenberg's reports that thyroxine induces strobilation and affects statolith development in a cnidarian , the jellyfish Aurelia [12, 13]. Now, however, thyroxine...