title: Marsupials and monotremes possess a novel family of MHC class I genes that is lost from the eutherian lineage.
abstract: BACKGROUND
  Major 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.
  
  
  RESULTS
  Application 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. papenfuss@wehi.edu.au.|Department of Medical Biology, University of Melbourne, Melbourne, VIC, 3010, Australia. papenfuss@wehi.edu.au.|Peter MacCallum Cancer Centre, East Melbourne, VIC, 3002, Australia. papenfuss@wehi.edu.au.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, 3010, Australia. papenfuss@wehi.edu.au.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Papenfuss
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, VIC, 3010, Australia.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM, 87131-0001, USA.
authors.forename: Katina
authors.initials: K
authors.lastname: Krasnec
authors.affiliation: Research School of Biology, Australian National University, Canberra, ACT, 2601, Australia.|Institute for Applied Ecology, University of Canberra, Canberra, ACT, 2601, Australia.
authors.forename: Janine E
authors.initials: JE
authors.lastname: Deakin
authors.affiliation: Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM, 87131-0001, USA.|Australian Animal Health Laboratory, CSIRO, East Geelong, VIC, 3219, Australia.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Baker
authors.affiliation: Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM, 87131-0001, USA. rdmiller@unm.edu.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Miller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001315:Australia; D001483:Base Sequence; D019143:Evolution, Molecular; D005805:Genes, MHC Class I; D016678:Genome; D006801:Humans; D008394:Marsupialia / Q000235:genetics*; D009007:Monotremata / Q000235:genetics*; D010802:Phylogeny