The complete structure of the rat thyroglobulin gene.

We have isolated the entire gene for rat thyroglobulin, the precursor for thyroid hormone biosynthesis. The gene is at least 170,000 base pairs (bp) long; 9000 bp of coding information are distributed in 42 exons of homogeneous size (150-200 bp) except for two exons of 1100 and 620 bp. The sequences coding for two major thyroxine-forming sites are localized in exons 2 and 39. These two sequences do not show any homology either at the DNA or at the protein-sequence level, even though they code for sites highly specialized for the same function. Furthermore, both the 3' and the 5' end of the thyroglobulin structural gene appear to be made of repetitive units, which again do not show any homology. On the basis of these observations, we propose that the thyroglobulin gene arose by shuffling of at least two segments, with different evolutionary histories, each of which already contained introns.