The Significance of Gene Duplication in Immunoglobulin Evolution (Epimethean Natural Selection and Promethean Evolution)

Abstract

Antibodies produced by B cells of man and other mammals are specified by three autosomally inherited gene clusters that are not linked to each other. The first cluster is for κ-type light (L) chains, while the second is for λ-type L chains. The third specifies various classes of heavy (H) chains (Grubb, 1970; Mage et al., 1973). Each cluster apparently contains a small number (1–10 or so) of constant (C)-region genes and a greater number (up to the order of 10²) of variable (V)-region genes (Hood et al., 1975). Inasmuch as L and H chains are the components of a single antibody molecule, the observed nonlinkage of relevant genes reveals that vertebrates are perfectly capable of coordinating the activities of nonlinked genes. In fact, the nonlinkage of coordinatedly regulated genes is a rule rather than an exception; i.e., hemoglobin α- and β-chain genes are not linked. Furthermore, even the observed close linkage between V-region and C-region genes within each cluster may be no functional prerequisite, merely reflecting their evolutionary origin in that they arose as tandem repeats of an ancestral gene. It now appears (see Greaves, 1975) that for their cell-bound antibodies or receptors, T cells also utilize the sameset of V-region genes as B cells, but they make use of an entirely different set of C-region genes that may reside within the major histocompatibility locus, i.e., H-2 of mice and HLA of man (Gally and Edelman, 1972). Indeed, the HLA gene complex of man, which is carried by chromosome 6, is not linked to any of the three gene clusters for immunoglobulins (Ig’s). Furthermore, the ß ₂-microglobulin locus is on yet another chromosome: chromosome 15 (Goodfellow et al., 1975).