A Novel Family of Major Histocompatibility Complex Class I Genes in Marsupials and Monotremes

The Major Histocompatibility Complex (MHC) class I family of genes encode for molecules that have well-conserved structures, but have evolved to perform a diverse functions. The availability of an opossum genome from the grey, short-tailed opossum, Monodelphis domestica, has allowed for analysis of MHC class I genes in a marsupial. Traditional methods for gene discovery uncovered 13 MHC class I genes in the opossum. Utilization of a novel method to search for MHC domain structures discovered a family of 17 novel MHC class I genes. These genes, named ModoUT1-17, were located in a cluster on chromosome 1, unlinked to the MHC. UT homologues are only found in marsupial and monotreme genomes, consistent with being ancient in mammals yet lost in eutherians. Twelve of the ModoUT loci are transcribed in the opossum thymus. The majority of UT transcription is in the thymus or skin, with limited expression in other tissues. Full-length sequencing of eleven transcribed ModoUT genes revealed between five and eight exons, with typical class I gene structure and few alternative splice variants. A survey of ModoUT polymorphism in different M. domestica populations found low levels of polymorphism. Limited positive selection occurs in any of the ModoUT genes, suggesting they may not be under pathogen-mediated pressure. Also uncovered in M. domestica genome search was the presence of two additional loci of the ModoUA gene, now designated ModoUA3 and ModoUA4. The ModoUA gene is thought to be the class I molecule involved in peptide presentation. These new genes were uncovered in a region of the genome that was expanded and more complete than in earlier genome assemblies. The occurrence of five to six alleles in individual M. domestica indicates three loci being transcribed. The ModoUA1 and ModoUA3 genes are highly similar and alleles cannot be distinguished, while ModoUA4 is easily identifiable, although less common and also relatively non-polymorphic and not under positive selection. The use of later assemblies and novel search methods confirmed the existence of three related MHC class I genes in the opossum, making opossums more typical of mammals by having multiple classical MHC class I loci.Center for Evolutionary and Theoretical ImmunologyBiologyDoctoralUniversity of New Mexico. Biology Dept.Miller, RobertSalinas, IreneTurner, TomCriscitiello, Michae