Class II multiformity generated by variable MHC-DRB region configurations in the California sea lion (Zalophus californianus)

In light of the immunological importance of molecules encoded within the major histocompatibility complex (MHC), there are numerous studies examining the variability of these genes in wildlife populations. An underlying assumption in many of these studies is that MHC diversity invariably arises from a high level of allelic variation at a single gene locus, leading to widespread descriptions of thriving species with apparently limited MHC polymorphism. Indeed, in a previous study we failed to find sequence features compatible with traditionally diverse peptide-binding functions in MHC class II (DQA and DQB) genes in California sea lions and therefore expanded the search for polymorphism to the DRA and DRB genes. Our results show that, in contrast to Zaca-DQA, -DQB, and -DRA, Zaca-DRB has sequence features compatible with antigen binding and presentation. In fact Zaca-DRB constitutes a gene family, comprising at least seven loci, each of which exhibits limited variability, and which are present in variable configurations between individuals. This unusual mechanism for generating MHC DRB diversity is similar to that observed in the rhesus macaque, but has not been reported in any other species. The identification of a novel system of class II MHC variability in the California sea lion justifies new studies into the organizational basis of immunogenetic diversity in other marine species, and its role in infectious disease susceptibility.