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

Parra ZE, Baker ML, Hathaway J, Lopez AM, Trujillo J, Sharp A, Miller RD - BMC Genomics (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Evolutionary and Theoretical Immunology and Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA. zulyep@unm.edu

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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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Map of the opossum TRB locus. TRBV (red), TRBD (orange), TRBJ (green) and TRBC (blue) are indicated. Transcriptional orientation, pseudogenes, and syntenic genes discussed in the text are indicated as in Figure 1.
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Figure 4: Map of the opossum TRB locus. TRBV (red), TRBD (orange), TRBJ (green) and TRBC (blue) are indicated. Transcriptional orientation, pseudogenes, and syntenic genes discussed in the text are indicated as in Figure 1.

Mentions: TRB has been physically mapped to chromosome 8q in the opossum [17]. The opossum TRB locus spans 400 kb making it smaller in size than its human and mouse homologues that are about 650 kb each (Figure 4) [31,22]. Genes syntenic the opossum TRB locus are also conserved across human, mouse, cow and chicken. These include the trypsinogen genes (TRY) found at the 5' and 3' ends of the TRB locus and intermixed between the TRBV and TRBC gene segments (Figure 4) [22]. The mono-oxygenase DBH-like 2 (DBHL) is found at the 5' end of the locus in the opossum, similar to human, mouse, and cow, but not in chicken. Genes such as kell blood group glycoprotein (Kel) and ephrin type-b receptor 6 precursor (EPHB6) found at the 3' end of the opossum TRB locus have conserved synteny in mammals and chicken (Figure 4). As with TRA/D, the TRB locus organization is highly conserved between opossum and eutherians. This is further illustrated by a TRBV segment (TRBV28 in opossum) located at the 3' end of the locus that is in the reverse orientation relative to the other gene segments. A clear orthologue of this gene segment is present in human (TRBV30) and mouse (TRBV31) making this an ancient arrangement (Figure 4 and group F in Figure 5).


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

Parra ZE, Baker ML, Hathaway J, Lopez AM, Trujillo J, Sharp A, Miller RD - BMC Genomics (2008)

Map of the opossum TRB locus. TRBV (red), TRBD (orange), TRBJ (green) and TRBC (blue) are indicated. Transcriptional orientation, pseudogenes, and syntenic genes discussed in the text are indicated as in Figure 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2275272&req=5

Figure 4: Map of the opossum TRB locus. TRBV (red), TRBD (orange), TRBJ (green) and TRBC (blue) are indicated. Transcriptional orientation, pseudogenes, and syntenic genes discussed in the text are indicated as in Figure 1.
Mentions: TRB has been physically mapped to chromosome 8q in the opossum [17]. The opossum TRB locus spans 400 kb making it smaller in size than its human and mouse homologues that are about 650 kb each (Figure 4) [31,22]. Genes syntenic the opossum TRB locus are also conserved across human, mouse, cow and chicken. These include the trypsinogen genes (TRY) found at the 5' and 3' ends of the TRB locus and intermixed between the TRBV and TRBC gene segments (Figure 4) [22]. The mono-oxygenase DBH-like 2 (DBHL) is found at the 5' end of the locus in the opossum, similar to human, mouse, and cow, but not in chicken. Genes such as kell blood group glycoprotein (Kel) and ephrin type-b receptor 6 precursor (EPHB6) found at the 3' end of the opossum TRB locus have conserved synteny in mammals and chicken (Figure 4). As with TRA/D, the TRB locus organization is highly conserved between opossum and eutherians. This is further illustrated by a TRBV segment (TRBV28 in opossum) located at the 3' end of the locus that is in the reverse orientation relative to the other gene segments. A clear orthologue of this gene segment is present in human (TRBV30) and mouse (TRBV31) making this an ancient arrangement (Figure 4 and group F in Figure 5).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Evolutionary and Theoretical Immunology and Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA. zulyep@unm.edu

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

Show MeSH