Molecular Cloning and Sequencing of cDNAs Encoding Three Heavy-Chain Precursors of the Inter- α-Trypsin Inhibitor in Syrian Hamster: Implications for the Evolution of the Inter-α-Trypsin Inhibitor Heavy Chain Family

: Complementary DNAs encoding precursors of the three heavy chains (HC1, HC2, HC3) of the inter-alpha-trypsin inhibitor in Syrian hamster liver were sequenced. The deduced amino acid sequence of the HC1 precursor was 87, 82, and 79% identical with those of the HC1 precursors from mouse, man and pig, respectively. The HC2 and HC3 precursors showed similar degrees of sequence identity with the corresponding human and mouse HC precursors. When the hamster HC1 precursor was compared with its own HC2 and HC3 precursors, however, even the most highly conserved segment consisting of 565 amino acid residues, i.e., about 2/3 of the whole molecule, showed only about 35 and 65% sequence identity, respectively. Essentially the same results were obtained on the intra-species comparisons of three subfamilies in man and mouse. Thus, the interspecies conservation of a given HC subfamily is much greater than the similarity between the three different HC subfamilies within a given species. These results suggest that (i) higher vertebrates possess three HC genes which have been evolving independently of each other under purifying selection; (ii) the diversification of the three HC subfamilies, for which the middle regions of the molecules were mainly responsible, occurred before eutherian radiation; and (iii) each HC subfamily may have unique function(s), although at present virtually nothing is known about the functional differences between the three HC subfamilies.