Immunoglobulin evolution: chemical study of clawed toad (Xenopus laevis) heavy and light chains.

NH2 terminal amino acid sequence determinations of clawed toad (Xenopus laevis) immunoglobulins indicate that approximately 30% of the heavy chains and less than 5% of the light chains have unblocked NH2 termini. The major amino acid sequence of the X. laevis 7S immunoglobulin heavy chains is the same as that of the 19S immunoglobulin heavy chains. Thus in the synthesis of the heavy chains, the VH genes coding for unblocked heavy chains can associate with CH genes of both the 19S and 7S classes. This association is particularly important in amphibians because, in contrast to mammals and birds, the majority of amphibian antibody-producing cells synthesize both 19S and 7S immunoglobulins and do not participate in the 'genetic switch' characteristic of lymphocyte differentiation in higher organisms. In X. laevis, the major amino acid sequence at the first twenty-four positions of the unblocked heavy chains shows approximately 54% difference from the prototype amino acid sequence of the mammalian VHIII subgroup. Thus, the VHIII gene(s) must have started to appear after the evolutionary divergence of the common ancestor of mammals and birds from the amphibian line. The amino acid composition of the X. Laevis 7S immunoglobulin heavy chains differs from that of its 19S immunoglobulins as well as those of human IgG and IgA. These data support the concepts (a) that amphibian 7S and 19S immunoglobins belong to distinct classes and (b) that amphibian 7S immunoglobulin does not resemble mammalian IgG or IgA.