Transspecies dimorphic allelic lineages of the proteasome subunit β-type 8 gene ( PSMB8 ) in the teleost genus Oryzias

Abstract

The proteasome subunit β-type 8 (PSMB8) gene in the jawed vertebrate MHC genomic region encodes a catalytic subunit of the immunoproteasome involved in the generation of peptides to be presented by the MHC class I molecules. A teleost, the medaka (Oryzias latipes), has highly diverged dimorphic allelic lineages of the PSMB8 gene with only about 80% amino acid identity, termed "PSMB8d" and "PSMB8N," which have been retained by most wild populations analyzed. To elucidate the evolutionary origin of these two allelic lineages, seven species of the genus Oryzias were analyzed for their PSMB8 allelic sequences using a large number of individuals from wild populations. All the PSMB8 alleles of these species were classified into one of these two allelic lineages based on their nucleotide sequences of exons and introns, indicating that the Oryzias PSMB8 gene has a truly dichotomous allelic lineage. Retention of both allelic lineages was confirmed except for one species. The PSMB8d lineage showed a higher frequency than the PSMB8N lineage in all seven species. The two allelic lineages showed curious substitutions at the 31st and 53rd residues of the mature peptide, probably involved in formation of the S1 pocket, suggesting that these allelic lineages show a functional difference in cleavage specificity. These results indicate that the PSMB8 dimorphism was established before speciation within the genus Oryzias and has been maintained for more than 30-60 million years under a strict and asymmetric balancing selection through several speciation events.long-term balancing selection | antigen processing | transspecies polymorphism T ransspecies polymorphism (TSP) is the passage of allelic lineages from ancestral to descendent species (1), and the underlying selective mechanism is referred to as balancing selection caused by "overdominant selection," "frequency-dependent selection," or "selection that varies in time and space" (2). The vertebrate MHC class I and II genes with a large number of alleles and wide allelic differences provide a classical example of TSP (3, 4), most probably arising by overdominant selection (5). TSP of the MHC genes sometimes persists for very long periods. Certain HLA-DRB alleles are reported to have persisted for 50-60 million years (6). Another well-characterized TSP has been reported for the rabbit Ig heavy-chain variable-region genes; its persistence has been estimated at 50 million years based on molecular phylogenetic analysis (7,8). Except for these genes encoding molecules showing high degree of binding specificity, information for long-term balancing selection resulting in TSP is limited (9-11). Moreover, all TSP reported thus far involve only a few species, and the possible presence of a long-lasting TSP surviving through many speciation events is still to be clarified by systematic phylogenetic analysis.The MHC class I molecules deliver the peptides derived from cytosolic proteins to the cell surface for recognition by cytotoxic T cells. The proteins are degraded proteolytically into s...

Highly divergent dimorphic alleles of the proteasome subunit beta type-8 (PSMB8) gene of the bichir Polypterus senegalus: implication for evolution of the PSMB8 gene of jawed vertebrates

“…The PSMB8F lineage seems to have been lost in humans, Xenopus, and Oryzias. However, the F type alleles apparently revived within the PSMB8A lineage in Xenopus and Oryzias, and the revived PSMB8 dimorphism showed transspecies polymorphisms in these genera (Nonaka et al 2000;Miura et al 2010). However, the evolutionary events that revived the PSMB8 dimorphism in Xenopus and Oryzias seem to be independent of each other and, of course, of the generation of the two ancient lineages.…”

“…Overdominance-type balancing selection provides a plausible explanation for the dimorphism with the chymotrypsin-like and elastase-like specificities, which could cope with separate pathogens. The persistence time of the transspecies dimorphism of the PSMB8 gene in Xenopus and Oryzias species has been estimated to be 30-80 million years (Miura et al 2010;Nonaka et al 2000), locating them among the longest balancing selections reported to date. The persistence time of the PSMB8 dimorphism found in bichir remains to be clarified.…”

“…Because the A and F types of Xenopus (Nonaka et al 2000) and Oryzias PSMB8 (Miura et al 2010) are alleles, while those of sharks are predicted to be paralogs (Kandil et al 1996), 28 offspring of bichir generated from the crossing of one pair were typed for the PSMB8 gene to clarify whether the bichir A and F types are alleles or paralogs. We typed these samples by PCR using genomic DNA extracted from the caudal fins with type-specific primers (Fig.…”

“…To date, highly divergent dichotomous alleles of PSMB8 have been reported in Oryzias species (actinopterygian teleosts) (Miura et al 2010) and Xenopus species (sarcopterygian amphibians) (Nonaka et al 2000). Interestingly, these dimorphic alleles share a similar substitution at the 31st position of the mature protein, which is most probably involved in formation of the S1 pocket (Unno et al 2002).…”

“…Phylogenetic analysis showed that the origins of the PSMB8 dimorphism of Oryzias and Xenopus species were independent of each other despite the similar substitution at the 31st position of the mature protein (Tsukamoto et al 2005). Once established, however, these dimorphic alleles were transferred from ancestral to descendent species for more than 30-60 million years in Oryzias (Miura et al 2010) and more than 80 million years in Xenopus (Nonaka et al 2000). These dimorphisms are examples of transspecies polymorphisms maintained by long-term balancing selection.…”