Organization of DH-Gene Locus is Distinct in Cattle

Some cattle antibodies are amongst the largest known to exist, in a species where CDR3 of the heavy-chain variable region (CDR3H) is of exceptional size as it may extend up to 61 amino acids. The origin of such an exceptionally long CDR3H in cattle antibodies is not yet understood. For these reasons, we have completely characterized DH gene locus in a Holstein cow. In contrast to other species, such as mice and humans, the DH gene locus in cattle, extending over 68 kb, is organized in subclusters comprising two to four DH gene segments. Analysis of DH genes reveals the presence of characteristic repetitive GGT and TAT codons. No evidence for a DH gene segment longer than 148 base pairs has been noted. Therefore, mechanistic factors contribute significantly to CDR3H size generation. Such comparative genomics perspectives of bovine D gene loci have revealed the complexity of evolution, across animal phyla, of functional significance in the generation of antibody diversity.