Conservation of an immunoglobulin variable-region gene family indicates a specific, noncoding function.

Blot-hybridization and DNA sequence analyses reveal the particular evolutionary conservation of a group of immunoglobulin heavy-chain variable-region (VH) genes in all mammalian species examined. These particular genes are group III genes--the VH7183 family in the mouse and the homologous VH III family in human. This conservation is localized to sequences encoding framework regions 1 and 3 of the antibody variable region and is exerted at the nucleotide level. Because selection acting at the amino acid level alone cannot explain the conservation of these sequences, these sequences must have a noncoding function. The preferential rearrangement of VH7183 and VH III genes, together with the similarity of the conserved sequences to elements implicated in recombination in other systems, suggest that these sequences function to target the series of rearrangements that assemble complete immunoglobulin genes.