Gene Expansion and Antibody Variability

SUMMARY The amino acid sequence near the N‐terminus of a human immunoglobulin (Ig) light (L) chain has been determined. This sequence is more homologous to avian Ig L chains than to human Ig L chains, and defines an additional variable (V‐) region subgroup designated as VλVI. These data also suggest that all vertebrates share large numbers of Ig V‐region genes and that 'species‐specific’residues reflect the expression in different species of different sets of V‐region genes. Control at a level equivalent to ‘regulatory genes’ * determines which genes are expressed. Our findings raise a question concerning the possible role of redundant DNA, in that at least some of the ‘nonsense’ DNA in one species may actually be 'sense’DNA in another. We hypothesize that in evolution‘gene expansion’is a regular mechanism for the generation of new genes and that different members of a given group of repetitious genes are expressed in different species. Such a phenomenon is basically similar to the‘mechanism’controlling the differential expression of genes during embryonic differentiation. Our hypothesis differs from the previous version of the germ‐line hypothesis proposed for genetic control of antibody variability which involves ‘sudden excessive gene expansion and contraction’. Evidence suggesting that the‘gene expansion’mechanism may also be applicable to a lesser degree to other gene systems is briefly reviewed and discussed.