Evolutionary Origins of Immunoglobulin Gene Diversity

Abstract

During the past several years, our laboratory has identified immunoglobulin genes in species that represent major phylogenetic groups of vertebrates (Litman et al. 1989). Taken together, the descriptions of immunoglobulin genes in chondrichthyes (Litman et al. 1985a; Hinds and Litman 1986; Kokubu et al 1988a), bony fishes (Amemiya and Litman 1990, 1991), amphibians (Schwager et al. 1988b, 1989; Haire et al. 1990, 1991), avians (Reynaud et al. 1987, 1989) and mammals (Blackwell and Alt 1988), as well as ongoing studies in our laboratory involving other phylogenetically important species are revealing, the overall patterns in the evolution of immunoglobulin gene structure and diversity. In all of these species, segmental organization and DNA sequence-mediated selective rearrangement in somatic tissues, the most distinctive features of the immunoglobulin gene system, are conserved. The nucleotide and predicted peptide sequences of individual V_H, V_L, D_H, J_H, J_L and some C_H exons, in most instances, are highly conserved as are the recombination signal sequences (RSSs) flanking the V_H, V_L, D_H, J_H and J_L segmental elements (Litman et al. 1985a; Hinds and Litman 1986; Kokubu et al. 1988a). In addition, the exon-intron organization of the C_H exons in Heterodontus (horned shark), a phylogenetically primitive vertebrate, as well as other chondrichthyes (see below), is equivalent to that described in mammals (Kokubu et al. 1988b). To a certain degree, some of these findings are not unexpected since in many cases the genes in lower vertebrates were detected by cross-hybridization with a mammalian immunoglobulin heavy chain variable region gene-specific probe (Litman et al. 1983, 1985a). Typically, any gene detected using this procedure would have to be at least 60% related at the nucleotide sequence level. Although it is informative to compare the sequences of these genes to one another in an overall sense, it must be emphasized that the V_H genes are members of extensively diversified multigene families and few guidelines can be applied to determine whether similarities and/or differences in gene sequence reflect orthologous evolutionary relationships (Litman et al. 1985b).