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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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Diagram of possible scenarios for the origin of TRM. Non-homologous recombination between ancient IgH and TCR loci gave rise to a hybrid locus. A duplication event of part of the hybrid locus presumably created and additional set of V, D and J gene segments. Subsequently two possible alternatives are given for the origin of TRMVj. Left panel: A V(D)J recombination in germ cells followed by deletion of the intron located within the sequence encoding the leader peptide. Right panel: A V(D)J recombination event occurs in somatic cells, followed by transcription and splicing, resulting in a complete mRNA transcript. This mRNA was reverse transcribed to DNA by a reverse transcriptase and it was inserted back into the genome by homologous recombination. V, D and J gene segments and C regions are color-coded as in previous figures. TRMV and TRMVj are distinguished as red or yellow color, respectively. The exon encoding leader peptide is indicated with an L.
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Figure 10: Diagram of possible scenarios for the origin of TRM. Non-homologous recombination between ancient IgH and TCR loci gave rise to a hybrid locus. A duplication event of part of the hybrid locus presumably created and additional set of V, D and J gene segments. Subsequently two possible alternatives are given for the origin of TRMVj. Left panel: A V(D)J recombination in germ cells followed by deletion of the intron located within the sequence encoding the leader peptide. Right panel: A V(D)J recombination event occurs in somatic cells, followed by transcription and splicing, resulting in a complete mRNA transcript. This mRNA was reverse transcribed to DNA by a reverse transcriptase and it was inserted back into the genome by homologous recombination. V, D and J gene segments and C regions are color-coded as in previous figures. TRMV and TRMVj are distinguished as red or yellow color, respectively. The exon encoding leader peptide is indicated with an L.

Mentions: In spite of detailed analyses of the opossum conventional TCR loci, the origins of TRM remain enigmatic. The current evidence support the following conclusions and model for the origin of TRM: 1) There likely was a recombination or insertion event between an IgH and TCR locus (Figure 10); 2) The TCR locus involved was most likely TRD or a TRD-like based on sequence similarity [14]. Unfortunately the highly conserved and stable organization of the TRA/D region across birds and mammals does not provide clues as to how TRD might have participated in the origins of TRM; 3) The IGH-TCR hybrid formed likely underwent a whole or partial duplication event giving rise to multiple sets of V, D, and J elements one of which remained unrearranged in the germline, the other becoming germline joined either through direct RAG mediated V(D)J recombination in the germline (left-hand path in Figure 10) or through retrotransposition (right-hand path in Figure 10). Ongoing analyses of the TRM locus in the platypus may yield further insights into these possible scenarios for the origins of this unusual TCR chain.


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)

Diagram of possible scenarios for the origin of TRM. Non-homologous recombination between ancient IgH and TCR loci gave rise to a hybrid locus. A duplication event of part of the hybrid locus presumably created and additional set of V, D and J gene segments. Subsequently two possible alternatives are given for the origin of TRMVj. Left panel: A V(D)J recombination in germ cells followed by deletion of the intron located within the sequence encoding the leader peptide. Right panel: A V(D)J recombination event occurs in somatic cells, followed by transcription and splicing, resulting in a complete mRNA transcript. This mRNA was reverse transcribed to DNA by a reverse transcriptase and it was inserted back into the genome by homologous recombination. V, D and J gene segments and C regions are color-coded as in previous figures. TRMV and TRMVj are distinguished as red or yellow color, respectively. The exon encoding leader peptide is indicated with an L.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 10: Diagram of possible scenarios for the origin of TRM. Non-homologous recombination between ancient IgH and TCR loci gave rise to a hybrid locus. A duplication event of part of the hybrid locus presumably created and additional set of V, D and J gene segments. Subsequently two possible alternatives are given for the origin of TRMVj. Left panel: A V(D)J recombination in germ cells followed by deletion of the intron located within the sequence encoding the leader peptide. Right panel: A V(D)J recombination event occurs in somatic cells, followed by transcription and splicing, resulting in a complete mRNA transcript. This mRNA was reverse transcribed to DNA by a reverse transcriptase and it was inserted back into the genome by homologous recombination. V, D and J gene segments and C regions are color-coded as in previous figures. TRMV and TRMVj are distinguished as red or yellow color, respectively. The exon encoding leader peptide is indicated with an L.
Mentions: In spite of detailed analyses of the opossum conventional TCR loci, the origins of TRM remain enigmatic. The current evidence support the following conclusions and model for the origin of TRM: 1) There likely was a recombination or insertion event between an IgH and TCR locus (Figure 10); 2) The TCR locus involved was most likely TRD or a TRD-like based on sequence similarity [14]. Unfortunately the highly conserved and stable organization of the TRA/D region across birds and mammals does not provide clues as to how TRD might have participated in the origins of TRM; 3) The IGH-TCR hybrid formed likely underwent a whole or partial duplication event giving rise to multiple sets of V, D, and J elements one of which remained unrearranged in the germline, the other becoming germline joined either through direct RAG mediated V(D)J recombination in the germline (left-hand path in Figure 10) or through retrotransposition (right-hand path in Figure 10). Ongoing analyses of the TRM locus in the platypus may yield further insights into these possible scenarios for the origins of this unusual TCR chain.

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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