Localized deletion-insertion mutations: a major factor in the evolution of immunoglobulin structural variability.

New and previously published amino acid sequences of mouse Vk chains completed to Trp35 were examined. This sequence includes a framework loop from NH2 to Cys23 and an antigen contacting complementarity region L1 which lies between Cys23 and Trp35. There are many different sequence variations from NH2 to Cys23 among BALB/c mouse Vk chains indicating multigenic control. Coordinately there is a remarkable structural heterogeneity of L1 size and sequence. Thus far chains with the same NH2-Cys23 sequence have similar sized L1, which suggests a close relationship between L1 size and characteristic NH2-Cys23 sequence. In this multigenic system selection for chains with size variations in L1 appears to have occurred. The mutational process that inserts or deletes triplets in this region is thought to be exploited in the derivation of new useful structural genes.