Characterization of the Z lineage Major histocompatability complex class I genes in zebrafish

Abstract

Zebrafish (Danio rerio) are a valuable model for studying immunity, infection, and hematopoietic disease and have recently been employed for transplantation assays. However, the lack of syngeneic zebrafish creates challenges with identifying immune-matched individuals. The MHC class I genes, which mediate allogeneic recognition in mammals, have been grouped into three broad lineages in zebrafish: the classical U genes on chromosome 19, the Z genes which have been reported to map to chromosome 1, and the L genes that map to multiple loci. Transplantations between individual zebrafish that are matched at the U locus fail to consistently engraft suggesting that additional loci contribute to allogeneic recognition. Although two full-length zebrafish Z transcripts have been described, the genomic organization and diversity of these genes have not been reported. Herein we define ten Z genes on chromosomes 1 and 3 and on an unplaced genomic scaffold. We report that neither of the Z transcripts previously described match the current genome assembly and classify these transcripts as additional gene loci. We characterize full-length transcripts for 9 of these 12 genes. We demonstrate a high level of expression variation of the Z genes between individual zebrafish suggestive of haplotypic variation. We report low level sequence variation for individual Z genes between individual zebrafish reflecting a possible nonclassical function, although these molecules may still contribute to allogeneic recognition. Finally, we present a gene nomenclature system for the Z genes consistent with MHC nomenclature in other species and with the zebrafish gene nomenclature guidelines.