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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    • "Heavy chain D genes however appear to be lacking in marsupials. The T-cell receptor has been isolated in several marsupials and includes TCRa, TCRb, TCRd, and TCRg (Baker et al., 2001; Harrison et al., 2003; Parra et al., 2008; Zuccolotto et al., 2000), as well as the unique marsupial TCRm (Baker et al., 2005). In the first 24 h after birth in the gray short-tailed opossum ab T-cells appear, followed by gd T cells and then around two weeks later T-cells expressing TCRm appear (Parra et al., 2009). "
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