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MHC-linked and un-linked class I genes in the wallaby.

Siddle HV, Deakin JE, Coggill P, Hart E, Cheng Y, Wong ES, Harrow J, Beck S, Belov K - BMC Genomics (2009)

Bottom Line: MHC class I antigens are encoded by a rapidly evolving gene family comprising classical and non-classical genes that are found in all vertebrates and involved in diverse immune functions.The classical class I have moved away from antigen processing genes in eutherian mammals and the wallaby independently, but both lineages appear to have benefited from this loss of linkage by increasing the number of classical genes, perhaps enabling response to a wider range of pathogens.The discovery of non-classical orthologs between distantly related marsupial species is unusual for the rapidly evolving class I genes and may indicate an important marsupial specific function.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia. h.siddle@usyd.edu.au

ABSTRACT

Background: MHC class I antigens are encoded by a rapidly evolving gene family comprising classical and non-classical genes that are found in all vertebrates and involved in diverse immune functions. However, there is a fundamental difference between the organization of class I genes in mammals and non-mammals. Non-mammals have a single classical gene responsible for antigen presentation, which is linked to the antigen processing genes, including TAP. This organization allows co-evolution of advantageous class Ia/TAP haplotypes. In contrast, mammals have multiple classical genes within the MHC, which are separated from the antigen processing genes by class III genes. It has been hypothesized that separation of classical class I genes from antigen processing genes in mammals allowed them to duplicate. We investigated this hypothesis by characterizing the class I genes of the tammar wallaby, a model marsupial that has a novel MHC organization, with class I genes located within the MHC and 10 other chromosomal locations.

Results: Sequence analysis of 14 BACs containing 15 class I genes revealed that nine class I genes, including one to three classical class I, are not linked to the MHC but are scattered throughout the genome. Kangaroo Endogenous Retroviruses (KERVs) were identified flanking the MHC un-linked class I. The wallaby MHC contains four non-classical class I, interspersed with antigen processing genes. Clear orthologs of non-classical class I are conserved in distant marsupial lineages.

Conclusion: We demonstrate that classical class I genes are not linked to antigen processing genes in the wallaby and provide evidence that retroviral elements were involved in their movement. The presence of retroviral elements most likely facilitated the formation of recombination hotspots and subsequent diversification of class I genes. The classical class I have moved away from antigen processing genes in eutherian mammals and the wallaby independently, but both lineages appear to have benefited from this loss of linkage by increasing the number of classical genes, perhaps enabling response to a wider range of pathogens. The discovery of non-classical orthologs between distantly related marsupial species is unusual for the rapidly evolving class I genes and may indicate an important marsupial specific function.

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Neighbour-joining phylogenetic analysis of the relationship between marsupial class I genes. Bootstrap support for branches is provided. Estimated divergence times are indicated adjacent to the relevant node. The tammar wallaby class I sequences Maeu-I*01 and Maeu-I*02 are cDNA transcripts from Genbank. The phylogenetic tree is divided into the following clades; clade 1 includes MHC un-linked wallaby class I genes and expressed class I transcripts from Australian marsupials, clade 2 includes opossum class I genes only, including opossum class Ia (Modo-UA, UB and UC), clade 3 includes marsupial specific class I genes from both the American and Australian lineages.
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Figure 2: Neighbour-joining phylogenetic analysis of the relationship between marsupial class I genes. Bootstrap support for branches is provided. Estimated divergence times are indicated adjacent to the relevant node. The tammar wallaby class I sequences Maeu-I*01 and Maeu-I*02 are cDNA transcripts from Genbank. The phylogenetic tree is divided into the following clades; clade 1 includes MHC un-linked wallaby class I genes and expressed class I transcripts from Australian marsupials, clade 2 includes opossum class I genes only, including opossum class Ia (Modo-UA, UB and UC), clade 3 includes marsupial specific class I genes from both the American and Australian lineages.

Mentions: The MHC un-linked class I genes group together (clade 1), in a phylogenetic analysis, while MHC-linked class I genes on chromosome 2q form a separate and distinct clade (clade 3) (Figure 2). Again, Maeu-UP is an exception, occupying the basal position in clade 1. Although the position of Maeu-UP is not well supported using neighbour joining (Figure 2) or Bayesian analysis (Additional file 3: Phylogenetic tree showing divergence times for tammar wallaby class I genes and Additional file 4: Phylogenetic tree produced for BEAST analysis) both methods produced trees with the same topology. Clade 1 also contains previously identified expressed class I transcripts from the Australian marsupials including the red-necked wallaby (Macropus rufogriseus), brushtail possum (Trichosurus vulpecula), Tasmanian devil (Sarcophilus harrisii) and tammar wallaby. Opossum class I sequences, including the Modo-UA (class Ia) and Modo-UG (class Ib) form a sister clade (clade 2) to the MHC un-linked tammar wallaby class I genes. Interestingly, clade 3 contains the tammar wallaby MHC-linked class I genes (Maeu-UE, Maeu-UO, Maeu-UK, Maeu-UM and Maeu-UL), two class I sequences isolated from the brushtail possum(Trichosurus vulpecula) and the majority of the opossum class Ib sequences. This clade is basal to the opossum class Ia sequences and MHC un-linked tammar wallaby class I sequences.


MHC-linked and un-linked class I genes in the wallaby.

Siddle HV, Deakin JE, Coggill P, Hart E, Cheng Y, Wong ES, Harrow J, Beck S, Belov K - BMC Genomics (2009)

Neighbour-joining phylogenetic analysis of the relationship between marsupial class I genes. Bootstrap support for branches is provided. Estimated divergence times are indicated adjacent to the relevant node. The tammar wallaby class I sequences Maeu-I*01 and Maeu-I*02 are cDNA transcripts from Genbank. The phylogenetic tree is divided into the following clades; clade 1 includes MHC un-linked wallaby class I genes and expressed class I transcripts from Australian marsupials, clade 2 includes opossum class I genes only, including opossum class Ia (Modo-UA, UB and UC), clade 3 includes marsupial specific class I genes from both the American and Australian lineages.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2719672&req=5

Figure 2: Neighbour-joining phylogenetic analysis of the relationship between marsupial class I genes. Bootstrap support for branches is provided. Estimated divergence times are indicated adjacent to the relevant node. The tammar wallaby class I sequences Maeu-I*01 and Maeu-I*02 are cDNA transcripts from Genbank. The phylogenetic tree is divided into the following clades; clade 1 includes MHC un-linked wallaby class I genes and expressed class I transcripts from Australian marsupials, clade 2 includes opossum class I genes only, including opossum class Ia (Modo-UA, UB and UC), clade 3 includes marsupial specific class I genes from both the American and Australian lineages.
Mentions: The MHC un-linked class I genes group together (clade 1), in a phylogenetic analysis, while MHC-linked class I genes on chromosome 2q form a separate and distinct clade (clade 3) (Figure 2). Again, Maeu-UP is an exception, occupying the basal position in clade 1. Although the position of Maeu-UP is not well supported using neighbour joining (Figure 2) or Bayesian analysis (Additional file 3: Phylogenetic tree showing divergence times for tammar wallaby class I genes and Additional file 4: Phylogenetic tree produced for BEAST analysis) both methods produced trees with the same topology. Clade 1 also contains previously identified expressed class I transcripts from the Australian marsupials including the red-necked wallaby (Macropus rufogriseus), brushtail possum (Trichosurus vulpecula), Tasmanian devil (Sarcophilus harrisii) and tammar wallaby. Opossum class I sequences, including the Modo-UA (class Ia) and Modo-UG (class Ib) form a sister clade (clade 2) to the MHC un-linked tammar wallaby class I genes. Interestingly, clade 3 contains the tammar wallaby MHC-linked class I genes (Maeu-UE, Maeu-UO, Maeu-UK, Maeu-UM and Maeu-UL), two class I sequences isolated from the brushtail possum(Trichosurus vulpecula) and the majority of the opossum class Ib sequences. This clade is basal to the opossum class Ia sequences and MHC un-linked tammar wallaby class I sequences.

Bottom Line: MHC class I antigens are encoded by a rapidly evolving gene family comprising classical and non-classical genes that are found in all vertebrates and involved in diverse immune functions.The classical class I have moved away from antigen processing genes in eutherian mammals and the wallaby independently, but both lineages appear to have benefited from this loss of linkage by increasing the number of classical genes, perhaps enabling response to a wider range of pathogens.The discovery of non-classical orthologs between distantly related marsupial species is unusual for the rapidly evolving class I genes and may indicate an important marsupial specific function.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia. h.siddle@usyd.edu.au

ABSTRACT

Background: MHC class I antigens are encoded by a rapidly evolving gene family comprising classical and non-classical genes that are found in all vertebrates and involved in diverse immune functions. However, there is a fundamental difference between the organization of class I genes in mammals and non-mammals. Non-mammals have a single classical gene responsible for antigen presentation, which is linked to the antigen processing genes, including TAP. This organization allows co-evolution of advantageous class Ia/TAP haplotypes. In contrast, mammals have multiple classical genes within the MHC, which are separated from the antigen processing genes by class III genes. It has been hypothesized that separation of classical class I genes from antigen processing genes in mammals allowed them to duplicate. We investigated this hypothesis by characterizing the class I genes of the tammar wallaby, a model marsupial that has a novel MHC organization, with class I genes located within the MHC and 10 other chromosomal locations.

Results: Sequence analysis of 14 BACs containing 15 class I genes revealed that nine class I genes, including one to three classical class I, are not linked to the MHC but are scattered throughout the genome. Kangaroo Endogenous Retroviruses (KERVs) were identified flanking the MHC un-linked class I. The wallaby MHC contains four non-classical class I, interspersed with antigen processing genes. Clear orthologs of non-classical class I are conserved in distant marsupial lineages.

Conclusion: We demonstrate that classical class I genes are not linked to antigen processing genes in the wallaby and provide evidence that retroviral elements were involved in their movement. The presence of retroviral elements most likely facilitated the formation of recombination hotspots and subsequent diversification of class I genes. The classical class I have moved away from antigen processing genes in eutherian mammals and the wallaby independently, but both lineages appear to have benefited from this loss of linkage by increasing the number of classical genes, perhaps enabling response to a wider range of pathogens. The discovery of non-classical orthologs between distantly related marsupial species is unusual for the rapidly evolving class I genes and may indicate an important marsupial specific function.

Show MeSH
Related in: MedlinePlus