MouseV(k) gene classification by nucleic acid sequence similarity

Analyses of immunoglobulin (Ig) variable (V) region gene usage in the immune response, estimates ofV gene germline complexity, and other nucleic acid hybridization-based studies depend on the extent to which such genes are related (i. e., sequence similarity) and their organization in gene families. While mouseIgh heavy chainV region (V (H)) gene families are relatively well-established, a corresponding systematic classification ofIgk light chainV region (V (k)) genes has not been reported. The present analysis, in the course of which we reviewed the known extent of theV (k) germline gene repertoire andV (k) gene usage in a variety of responses to foreign and self antigens, provides a classification of mouseV (k) genes in gene families composed of members with >80% overall nucleic acid sequence similarity. This classification differed in several aspects from that ofV (H) genes: only someV (k) gene families were as clearly separated (by >25% sequence dissimilarity) as typicalV (H) gene families; mostV (k) gene families were closely related and, in several instances, members from different families were very similar (>80%) over large sequence portions; frequently, classification by nucleic acid sequence similarity diverged from existing classifications based on amino-terminal protein sequence similarity. Our data have implications forV (k) gene analyses by nucleic acid hybridization and describe potentially important differences in sequence organization betweenV (H) andV (k) genes.