Original Paper


, Volume 65, Issue 2, pp 115-124

First online:

Exceptionally high conservation of the MHC class I-related gene, MR1, among mammals

  • Kentaro TsukamotoAffiliated withInstitute for Comprehensive Medical Science, Fujita Health University
  • , Janine E. DeakinAffiliated withDivision of Evolution, Ecology and Genetics, Research School of Biology, The Australian National University
  • , Jennifer A. Marshall GravesAffiliated withLa Trobe Institute of Molecular Sciences, La Trobe University
  • , Keiichiro HashimotoAffiliated withInstitute for Comprehensive Medical Science, Fujita Health University Email author 

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The major histocompatibility complex (MHC) class I-related gene, MR1, is a non-classical MHC class IA gene and is encoded outside the MHC region. The MR1 is responsible for activation of mucosal-associated invariant T (MAIT) cells expressing semi-invariant T cell receptors in the presence of bacteria, but its ligand has not been identified. A unique characteristic of MR1 is its high evolutionary conservation of the α1 and α2 domains corresponding to the peptide-binding domains of classical MHC class I molecules, showing about 90 % amino acid identity between human and mouse. To clarify the evolutionary history of MR1 and identify more critically conserved residues for the function of MR1, we searched for the MR1 gene using jawed vertebrate genome databases and isolated the MR1 cDNA sequences of marsupials (opossum and wallaby). A comparative genomic analysis indicated that MR1 is only present in placental and marsupial mammals and that the gene organization around MR1 is well conserved among analyzed jawed vertebrates. Moreover, the α1 and α2 domains, especially in amino acid residues presumably shaping a ligand-binding groove, were also highly conserved between placental and marsupial MR1. These findings suggest that the MR1 gene might have been established at its present location in a common ancestor of placental and marsupial mammals and that the shape of the putative ligand-binding groove in MR1 has been maintained, probably for presenting highly conserved component(s) of microbes to MAIT cells.


Major histocompatibility complex Non-classical MHC class I MR1 Molecular evolution