Comparative genomic analysis and evolution of the T cell receptor loci in the opossum Monodelphis domestica

Center for Evolutionary and Theoretical Immunology and Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA.
BMC Genomics (Impact Factor: 3.99). 02/2008; 9(1):111. DOI: 10.1186/1471-2164-9-111
Source: PubMed


All jawed-vertebrates have four T cell receptor (TCR) chains: alpha (TRA), beta (TRB), gamma (TRG) and delta (TRD). Marsupials appear unique by having an additional TCR: mu (TRM). The evolutionary origin of TRM and its relationship to other TCR remain obscure, and is confounded by previous results that support TRM being a hybrid between a TCR and immunoglobulin locus. The availability of the first marsupial genome sequence allows investigation of these evolutionary relationships.
The organization of the conventional TCR loci, encoding the TRA, TRB, TRG and TRD chains, in the opossum Monodelphis domestica are highly conserved with and of similar complexity to that of eutherians (placental mammals). There is a high degree of conserved synteny in the genomic regions encoding the conventional TCR across mammals and birds. In contrast the chromosomal region containing TRM is not well conserved across mammals. None of the conventional TCR loci contain variable region gene segments with homology to those found in TRM; rather TRM variable genes are most similar to that of immunoglobulin heavy chain genes.
Complete genomic analyses of the opossum TCR loci continue to support an origin of TRM as a hybrid between a TCR and immunoglobulin locus. None of the conventional TCR loci contain evidence that such a recombination event occurred, rather they demonstrate a high degree of stability across distantly related mammals. TRM, therefore, appears to be derived from receptor genes no longer extant in placental mammals. These analyses provide the first genomic scale structural detail of marsupial TCR genes, a lineage of mammals used as models of early development and human disease.

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    • "Primary TCR V–J rearrangments generally use J segments towards the 5 0 -end of the array and can progressively use downstream J in subsequent rearrangements. There is also a single V gene in reverse transcriptional orientation between the platypus C gene and the J array that is conserved in mammalian TCR/ both in location and orientation (Parra et al. 2008). There are 99 conventional TCR V gene segments in the platypus TCR/ locus, 89 of which share nucleotide identity with V in other species and 10 that share identity with V genes. "
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    ABSTRACT: The specific recognition of antigen by T cells is critical to the generation of adaptive immune responses in vertebrates. T cells recognize antigen using a somatically diversified T-cell receptor (TCR). All jawed vertebrates use four TCR chains called α, β, γ, and δ, which are expressed as either a αβ or γδ heterodimer. Nonplacental mammals (monotremes and marsupials) are unusual in that their genomes encode a fifth TCR chain, called TCRµ, whose function is not known but is also somatically diversified like the conventional chains. The origins of TCRµ are also unclear, although it appears distantly related to TCRδ. Recent analysis of avian and amphibian genomes has provided insight into a model for understanding the evolution of the TCRδ genes in tetrapods that was not evident from humans, mice, or other commonly studied placental (eutherian) mammals. An analysis of the genes encoding the TCRδ chains in the duckbill platypus revealed the presence of a highly divergent variable (V) gene, indistinguishable from immunoglobulin heavy (IgH) chain V genes (VH) and related to V genes used in TCRµ. They are expressed as part of TCRδ repertoire (VHδ) and similar to what has been found in frogs and birds. This, however, is the first time a VHδ has been found in a mammal and provides a critical link in reconstructing the evolutionary history of TCRµ. The current structure of TCRδ and TCRµ genes in tetrapods suggests ancient and possibly recurring translocations of gene segments between the IgH and TCRδ genes, as well as translocations of TCRδ genes out of the TCRα/δ locus early in mammals, creating the TCRµ locus.
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    • "However, the identification of large lymphocytes in the quokka and Virginia opossum in the first days after birth (Cutts and Krause, 1980; Rowlands et al., 1964; Yadav et al., 1972b) may provide some clues. Although the lymphocytes were not further classified in the former studies, Parra et al. (2008) detected a T cell receptor transcript isoform in gray-short tailed opossum as young as 1 day old, suggesting that they at least have cells committed to becoming lymphocytes even though they may not be functionally mature at this stage. Alternatively , the large lymphocytes could be NKC—lymphocytes that kill different types of cancer and virus infected cells. "
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    • "Sequences of the *01 allele of human, mouse, frog, and trout TCR Vβ gene segments (lacking the signal peptide) were downloaded from the IMGT database (Lefranc et al., 2009). DNA sequences of opossum TCR Vβ gene segments were isolated from the genome sequence (MonDom5) using published coordinates (Parra et al., 2008) and electronically translated in reading frame 1. The region of the Vβ surrounding CDR2 from in human, mouse, opossum, frog, and trout gene segments were isolated and searched for a YxYxxxxxx motif using the 3of5 web application (Seiler et al., 2006). "
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