Whole genome duplications have provided teleosts with many roads to peptide loaded MHC class I molecules

Unni Grimholt

doi:10.1186/s12862-018-1138-9

Abstract

BackgroundIn sharks, chickens, rats, frogs, medaka and zebrafish there is haplotypic variation in MHC class I and closely linked genes involved in antigen processing, peptide translocation and peptide loading. At least in chicken, such MHCIa haplotypes of MHCIa, TAP2 and Tapasin are shown to influence the repertoire of pathogen epitopes being presented to CD8+ T-cells with subsequent effect on cell-mediated immune responses.ResultsExamining MHCI haplotype variation in Atlantic salmon using transcriptome and genome resources we found little evidence for polymorphism in antigen processing genes closely linked to the classical MHCIa genes. Looking at other genes involved in MHCI assembly and antigen processing we found retention of functional gene duplicates originating from the second vertebrate genome duplication event providing cyprinids, salmonids, and neoteleosts with the potential of several different peptide-loading complexes. One of these gene duplications has also been retained in the tetrapod lineage with orthologs in frogs, birds and opossum.ConclusionWe postulate that the unique salmonid whole genome duplication (SGD) is responsible for eliminating haplotypic content in the paralog MHCIa regions possibly due to frequent recombination and reorganization events at early stages after the SGD. In return, multiple rounds of whole genome duplications has provided Atlantic salmon, other teleosts and even lower vertebrates with alternative peptide loading complexes. How this affects antigen presentation remains to be established.

Highlights

In sharks, chickens, rats, frogs, medaka and zebrafish there is haplotypic variation in Major histocompatibility complex (MHC) class I and closely linked genes involved in antigen processing, peptide translocation and peptide loading
To investigate functional MHCIa-linked polymorphism in salmonids we looked at available genomes from Atlantic salmon [39], rainbow trout ([40] and unpublished assembly) and coho salmon as well as Northern pike [41], a species basal to the salmonids that has not experienced the salmonid whole genome duplication event
PSMB8F linked haplotypes Based on data from medaka [33, 43, 44] and zebrafish [31], a good marker for functional teleost MHCIa haplotypes is the PSMB8F gene variant

Summary

Introduction

Chickens, rats, frogs, medaka and zebrafish there is haplotypic variation in MHC class I and closely linked genes involved in antigen processing, peptide translocation and peptide loading. Our view of antigen processing, peptide loading and peptide presentation in teleosts mainly relies on extrapolation of functional data generated in humans, a few other mammals and chickens In these species Major histocompatibility complex class I (MHCI) molecules are key players in discriminating self from non-self. Classical MHCI (MHCIa) molecules, consisting of an alpha chain and a noncovalently associated beta2-microglobulin (b2m) chain, are displayed at the surface of most cells where they normally present peptides derived from self-molecules chopped into smaller fragments in the cytoplasm. If foreign elements such as viruses are present in the cytoplasm, they are prone for degradation and presentation by MHCIa molecules. To form the peptide-loading complex, the CALR and ERp57-stabilized MHCIa molecule associates with tapasin (TAPBP) and the transporters

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