Marsupials and monotremes possess a novel family of MHC class I genes that is lost from the eutherian lineage

Abstract

BackgroundMajor histocompatibility complex (MHC) class I genes are found in the genomes of all jawed vertebrates. The evolution of this gene family is closely tied to the evolution of the vertebrate genome. Family members are frequently found in four paralogous regions, which were formed in two rounds of genome duplication in the early vertebrates, but in some species class Is have been subject to additional duplication or translocation, creating additional clusters. The gene family is traditionally grouped into two subtypes: classical MHC class I genes that are usually MHC-linked, highly polymorphic, expressed in a broad range of tissues and present endogenously-derived peptides to cytotoxic T-cells; and non-classical MHC class I genes generally have lower polymorphism, may have tissue-specific expression and have evolved to perform immune-related or non-immune functions. As immune genes can evolve rapidly and are subject to different selection pressure, we hypothesised that there may be divergent, as yet unannotated or uncharacterised class I genes.ResultsApplication of a novel method of sensitive genome searching of available vertebrate genome sequences revealed a new, extensive sub-family of divergent MHC class I genes, denoted as UT, which has not previously been characterized. These class I genes are found in both American and Australian marsupials, and in monotremes, at an evolutionary chromosomal breakpoint, but are not present in non-mammalian genomes and have been lost from the eutherian lineage. We show that UT family members are expressed in the thymus of the gray short-tailed opossum and in other immune tissues of several Australian marsupials. Structural homology modelling shows that the proteins encoded by this family are predicted to have an open, though short, antigen-binding groove.ConclusionsWe have identified a novel sub-family of putatively non-classical MHC class I genes that are specific to marsupials and monotremes. This family was present in the ancestral mammal and is found in extant marsupials and monotremes, but has been lost from the eutherian lineage. The function of this family is as yet unknown, however, their predicted structure may be consistent with presentation of antigens to T-cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1745-4) contains supplementary material, which is available to authorized users.

The UT family of MHC class I loci unique to non-eutherian mammals has limited polymorphism and tissue specific patterns of expression in the opossum

“…Another was a non-conventional TCR locus, TCRμ [32]. Both UT and TCRμ genes are found in marsupial and monotreme genomes, consistent with their presence in the last common ancestor of all living mammals [28, 33–35]. Neither of these gene families have been found in any eutherian mammal or non-mammalian genome to date, consistent with their being unique to mammals but lost in the eutherians [28, 33].…”

“…2). The variation in gene size does not correlate with phylogenetic relationship based on coding sequence, as highly related groups like ModoUT3, 4, 5, and 6 range from 5,453 bp to 12,219 bp [28]. …”

“…ModoUT8 was chosen as a model UT for further analysis as it was the first ModoUT uncovered, it demonstrates a limited transcription pattern like most opossum UT genes, it has clear orthologues in other marsupial species, and has the most generic structural similarity of the ModoUT molecules [28]. Cell specific transcription of ModoUT8 was investigated using fluorescence in situ hybridization (FISH).…”

“…One example is the UT family of MHC class I related genes [28]. Another was a non-conventional TCR locus, TCRμ [32].…”

“…The availability of whole genome sequences from a variety of gnathostome lineages provides the information needed to discover new MHC class I genes and potentially new roles for these molecules. Recently, a new family of MHC class I loci called UT was found, and appears to be restricted to marsupials and monotremes [28]. The phylogenetic distribution is consistent with having emerged early in mammalian evolution and subsequently lost in the eutherian lineage.…”