PHYLOGENETICALLY ASSOCIATED RESIDUES WITHIN THE VttllI SUBGROUP OF SEVERAL MAMMALIAN SPECIES EVIDENCE FOR A "PAucI-GENE" BASIS FOR ANTIBODY DIVERSITY* BY J. DONALD CAPRA,,

The origin of the amino acid sequence diversity characteristic of the variable (V) regions of immunoglobulins has been the subject of considerable controversy for several years. Two types of theories have been proposed to account for this diversity, primarily on the basis of sequence data derived from light chains. "Pauci-gene" theories assume that there are relatively few variable region genes in the germ llne and that the many different variable region sequences required for the humoral antibody response are generated by some somatic process (1-4). Multi-gene, or germ line, theories assume, alternatively, that a full complement of variable region genes exists preformed in the germ line (5, 6). A clear choice between a paucior multi-gene theory will probably have to await direct analyses of lymphoid cell DNA. However, RNA hybridization studies that have been carried out to date (7, 8) have not settled the question unambiguously. Major challenges to the validity of multi-gene theories are their difficulty in explaining the origin and stability of the allotypic markers present in the variable regions of rabbit heavy chains and the finding of "species-specific residues" in immunoglobulin light chains (9). Completely satisfactory explanations of these features of ilnmunoglobulin structure have not yet been provided under multi-gene assumptions. The exact identity and distribution of the species-specific (or phylogenetically associated, ref. 10) residues have not been easy to determine because of the several variable region subgroups that are characteristic of the light chains of most species. The presence of the subgroups makes difficult the identification of such residues in pooled light chains from a single species, an approach that would be of enormous value in establishing their true significance.