Ancient Phylogenetic Beginnings of Immunoglobulin Hypermutation

Many structures and molecules closely related to those involved in the specific process of immunoglobulin (Ig) hypermutation existed before the appearance of primordial Ig genes. Consequently, these structures can be found even in animals and organisms distinct from vertebrates; likewise, homologues of hypermutation enzymes are present in a broad range of species, from bacteria to mammals. Our analysis, based predominantly on primary structure, demonstrates the existence of molecules similar to Ig domains, variable Ig domains (IGv), and antigen receptors (AR) in unicellular organisms, nonvertebrate metazoans, and nonvertebrate Coelomata, respectively. In addition, we deal here with some important structural properties of CDR1-like segments of the selected sponge adhesion molecule GCSAMS exhibiting chimerical Ig domain similarities, and demonstrate the occurrence of conserved regions corresponding to Ohno's modern intact primordial building block in the C-terminal part of IGv-related segments of nonvertebrate origin. The results of our analysis are also discussed with respect to the possible phylogeny of molecules preceding the hypothetical common antigen receptor ancestor.