Evolutionary Development of Immunoglobulin Gene Diversity

Abstract

In all jawed vertebrate species, antibody diversity is specified by an immunoglobulin monomeric structure consisting of two heavy chains and two light chains. Different immuno-globulin classes are associated with various polymeric configurations of the basic monomer. Immunoglobulin-like heterodimers also occur in the jawless vetebrates (cyclostomes) of which the only extant representatives are the lampreys and hagfishes (Varner and Litman, unpub-lished observations);^1-2 primary structure data that would firmly establish these as antibodies, however, are not available presently. During the past several years, our labora-tory has identified immunoglobulin genes in species that are considered to represent signifi-cant departure points in vertebrate phylogeny.³ Taken together with the descriptions of im-munoglobulin genes in avians^4,5 and mammals,⁶ a reasonably complete picture of the over-all evolution of immunoglobulin gene structure and diversity is emerging. In all of these species, the most distinctive features of the immunoglobulin gene system, segmental organiza-tion and selective rearrangement in somatic tissues, are preserved. The structures of indivi-dual heavy chain variable (V_H), diversity (D_R), joining (J_H) and certain constant region (C_R) segmental elements are also remarkably similar. Two additional features of higher, vertebrate immunoglobulin genomic organization, the split leader and recombination signal sequences (RSSs), also are found in lower vertebrates. Furthermore, the exon-intron organization of the constant region found in Heterodontus (horned shark), the most phylogenetically primitive vertebrate studied thus far, is equivalent to that described in mammals.⁷ To a certain degree, some of these findings are not unexpected since in many cases the genes in lower vetebrates were detected by cross-hybridization with a particular mammalian immunoglobulin heavy chain gene probe.^8,9