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

Hannah Siddle, Janine Deakin, Penny Coggill, Elizabeth Hart, Yuanyuan Cheng, Emily Wong, Jennifer Harrow, Stephan Beck, Katherine Belov

    Research output: Contribution to journalArticle

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    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 rocessing 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 istantly related marsupial species is unusual for the rapidly evolving class I genes and may indicate an important marsupial specific function.
    Original languageEnglish
    Pages (from-to)1-15
    Number of pages15
    JournalBMC Genomics
    Volume10:310
    DOIs
    Publication statusPublished - 2009

    Fingerprint

    MHC Class I Genes
    Macropodidae
    Antigen Presentation
    Genes
    Marsupialia
    Mammals
    Histocompatibility Antigens Class I
    Endogenous Retroviruses
    Haplotypes
    Genetic Recombination
    Sequence Analysis
    Vertebrates

    Cite this

    Siddle, H., Deakin, J., Coggill, P., Hart, E., Cheng, Y., Wong, E., ... Belov, K. (2009). MHC-linked and un-linked class I genes in the wallaby. BMC Genomics, 10:310, 1-15. https://doi.org/10.1186/1471-2164-10-310
    Siddle, Hannah ; Deakin, Janine ; Coggill, Penny ; Hart, Elizabeth ; Cheng, Yuanyuan ; Wong, Emily ; Harrow, Jennifer ; Beck, Stephan ; Belov, Katherine. / MHC-linked and un-linked class I genes in the wallaby. In: BMC Genomics. 2009 ; Vol. 10:310. pp. 1-15.
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    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 rocessing 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 istantly related marsupial species is unusual for the rapidly evolving class I genes and may indicate an important marsupial specific function.",
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    Siddle, H, Deakin, J, Coggill, P, Hart, E, Cheng, Y, Wong, E, Harrow, J, Beck, S & Belov, K 2009, 'MHC-linked and un-linked class I genes in the wallaby', BMC Genomics, vol. 10:310, pp. 1-15. https://doi.org/10.1186/1471-2164-10-310

    MHC-linked and un-linked class I genes in the wallaby. / Siddle, Hannah; Deakin, Janine; Coggill, Penny; Hart, Elizabeth; Cheng, Yuanyuan; Wong, Emily; Harrow, Jennifer; Beck, Stephan; Belov, Katherine.

    In: BMC Genomics, Vol. 10:310, 2009, p. 1-15.

    Research output: Contribution to journalArticle

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    AU - Siddle, Hannah

    AU - Deakin, Janine

    AU - Coggill, Penny

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    AB - 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 rocessing 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 istantly related marsupial species is unusual for the rapidly evolving class I genes and may indicate an important marsupial specific function.

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