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Marsupials and monotremes possess a novel family of MHC class I genes that is lost from the eutherian lineage.

Papenfuss AT, Feng ZP, Krasnec K, Deakin JE, Baker ML, Miller RD - BMC Genomics (2015)

Bottom Line: Major histocompatibility complex (MHC) class I genes are found in the genomes of all jawed vertebrates.These class I genes are found in both American and Australian marsupials, and in monotremes, at an evolutionary chromosomal breakpoint, but are not present in non-mammalian genomes and have been lost from the eutherian lineage.This family was present in the ancestral mammal and is found in extant marsupials and monotremes, but has been lost from the eutherian lineage.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. papenfuss@wehi.edu.au.

ABSTRACT

Background: Major histocompatibility complex (MHC) class I genes are found in the genomes of all jawed vertebrates. The evolution of this gene family is closely tied to the evolution of the vertebrate genome. Family members are frequently found in four paralogous regions, which were formed in two rounds of genome duplication in the early vertebrates, but in some species class Is have been subject to additional duplication or translocation, creating additional clusters. The gene family is traditionally grouped into two subtypes: classical MHC class I genes that are usually MHC-linked, highly polymorphic, expressed in a broad range of tissues and present endogenously-derived peptides to cytotoxic T-cells; and non-classical MHC class I genes generally have lower polymorphism, may have tissue-specific expression and have evolved to perform immune-related or non-immune functions. As immune genes can evolve rapidly and are subject to different selection pressure, we hypothesised that there may be divergent, as yet unannotated or uncharacterised class I genes.

Results: Application of a novel method of sensitive genome searching of available vertebrate genome sequences revealed a new, extensive sub-family of divergent MHC class I genes, denoted as UT, which has not previously been characterized. These class I genes are found in both American and Australian marsupials, and in monotremes, at an evolutionary chromosomal breakpoint, but are not present in non-mammalian genomes and have been lost from the eutherian lineage. We show that UT family members are expressed in the thymus of the gray short-tailed opossum and in other immune tissues of several Australian marsupials. Structural homology modelling shows that the proteins encoded by this family are predicted to have an open, though short, antigen-binding groove.

Conclusions: We have identified a novel sub-family of putatively non-classical MHC class I genes that are specific to marsupials and monotremes. This family was present in the ancestral mammal and is found in extant marsupials and monotremes, but has been lost from the eutherian lineage. The function of this family is as yet unknown, however, their predicted structure may be consistent with presentation of antigens to T-cells.

No MeSH data available.


Sensitive pan-genome search for MHC class I genes. a The canonical domain structure of MHC class I proteins and (b) genes. c The location in the opossum genome and score of matches to profile hidden Markov models representing the antigen-presenting domain (split into α1 and α2 regions), C-type immunoglobulin domain and C-terminal domain. d Example of a high-scoring run of α1, α2, Ig and C-terminal domains in the opossum genome. e Finite state automata of the alignment algorithm to search for runs of α1, α2, Ig and C-terminal domains, taking domain score and distance between domains into account. The nodes (circles) show match states. Symbols on edges show scores/penalties: +m is the match score, which is based on the HMM match score; -γ is a distance-dependent affine gap penalty, which models introns and allows the alignment to skip over matches that interrupt a run of domains; -ψ is a constant penalty for dropping the C-terminal domain
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Fig1: Sensitive pan-genome search for MHC class I genes. a The canonical domain structure of MHC class I proteins and (b) genes. c The location in the opossum genome and score of matches to profile hidden Markov models representing the antigen-presenting domain (split into α1 and α2 regions), C-type immunoglobulin domain and C-terminal domain. d Example of a high-scoring run of α1, α2, Ig and C-terminal domains in the opossum genome. e Finite state automata of the alignment algorithm to search for runs of α1, α2, Ig and C-terminal domains, taking domain score and distance between domains into account. The nodes (circles) show match states. Symbols on edges show scores/penalties: +m is the match score, which is based on the HMM match score; -γ is a distance-dependent affine gap penalty, which models introns and allows the alignment to skip over matches that interrupt a run of domains; -ψ is a constant penalty for dropping the C-terminal domain

Mentions: Both classical and non-classical class I molecules have a conserved and distinctive protein domain structure. MHC class I genes typically have 5–9 exons encoding proteins with well-defined domain organization (Fig. 1a and 1b). The first exon encodes a signal peptide. Exons 2 and 3 encode the α1 and α2 domains, which together make up the antigen-presenting domain (APD). An immunoglobulin domain (Ig or α3) is encoded by exon 4. Additional exons may encode one or more transmembrane domains and the final exon contains a conserved cytoplasmic domain at the C-terminal of some MHC class I genes. The α1, α2 and Ig domains are the hallmark of MHC class I genes. However, different isoforms of some MHC class I genes exist. These may splice out some of these domains to produce other membrane bound versions of the protein or secreted forms. Additionally, the UL16-binding protein (ULBP) and retinoic acid early transcript (RAET) families, known in eutherians, are MHC class I-related genes that lack immunoglobulin domains and may utilize a GPI-anchor, rather than a transmembrane domain [12–15].Fig. 1


Marsupials and monotremes possess a novel family of MHC class I genes that is lost from the eutherian lineage.

Papenfuss AT, Feng ZP, Krasnec K, Deakin JE, Baker ML, Miller RD - BMC Genomics (2015)

Sensitive pan-genome search for MHC class I genes. a The canonical domain structure of MHC class I proteins and (b) genes. c The location in the opossum genome and score of matches to profile hidden Markov models representing the antigen-presenting domain (split into α1 and α2 regions), C-type immunoglobulin domain and C-terminal domain. d Example of a high-scoring run of α1, α2, Ig and C-terminal domains in the opossum genome. e Finite state automata of the alignment algorithm to search for runs of α1, α2, Ig and C-terminal domains, taking domain score and distance between domains into account. The nodes (circles) show match states. Symbols on edges show scores/penalties: +m is the match score, which is based on the HMM match score; -γ is a distance-dependent affine gap penalty, which models introns and allows the alignment to skip over matches that interrupt a run of domains; -ψ is a constant penalty for dropping the C-terminal domain
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4509613&req=5

Fig1: Sensitive pan-genome search for MHC class I genes. a The canonical domain structure of MHC class I proteins and (b) genes. c The location in the opossum genome and score of matches to profile hidden Markov models representing the antigen-presenting domain (split into α1 and α2 regions), C-type immunoglobulin domain and C-terminal domain. d Example of a high-scoring run of α1, α2, Ig and C-terminal domains in the opossum genome. e Finite state automata of the alignment algorithm to search for runs of α1, α2, Ig and C-terminal domains, taking domain score and distance between domains into account. The nodes (circles) show match states. Symbols on edges show scores/penalties: +m is the match score, which is based on the HMM match score; -γ is a distance-dependent affine gap penalty, which models introns and allows the alignment to skip over matches that interrupt a run of domains; -ψ is a constant penalty for dropping the C-terminal domain
Mentions: Both classical and non-classical class I molecules have a conserved and distinctive protein domain structure. MHC class I genes typically have 5–9 exons encoding proteins with well-defined domain organization (Fig. 1a and 1b). The first exon encodes a signal peptide. Exons 2 and 3 encode the α1 and α2 domains, which together make up the antigen-presenting domain (APD). An immunoglobulin domain (Ig or α3) is encoded by exon 4. Additional exons may encode one or more transmembrane domains and the final exon contains a conserved cytoplasmic domain at the C-terminal of some MHC class I genes. The α1, α2 and Ig domains are the hallmark of MHC class I genes. However, different isoforms of some MHC class I genes exist. These may splice out some of these domains to produce other membrane bound versions of the protein or secreted forms. Additionally, the UL16-binding protein (ULBP) and retinoic acid early transcript (RAET) families, known in eutherians, are MHC class I-related genes that lack immunoglobulin domains and may utilize a GPI-anchor, rather than a transmembrane domain [12–15].Fig. 1

Bottom Line: Major histocompatibility complex (MHC) class I genes are found in the genomes of all jawed vertebrates.These class I genes are found in both American and Australian marsupials, and in monotremes, at an evolutionary chromosomal breakpoint, but are not present in non-mammalian genomes and have been lost from the eutherian lineage.This family was present in the ancestral mammal and is found in extant marsupials and monotremes, but has been lost from the eutherian lineage.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. papenfuss@wehi.edu.au.

ABSTRACT

Background: Major histocompatibility complex (MHC) class I genes are found in the genomes of all jawed vertebrates. The evolution of this gene family is closely tied to the evolution of the vertebrate genome. Family members are frequently found in four paralogous regions, which were formed in two rounds of genome duplication in the early vertebrates, but in some species class Is have been subject to additional duplication or translocation, creating additional clusters. The gene family is traditionally grouped into two subtypes: classical MHC class I genes that are usually MHC-linked, highly polymorphic, expressed in a broad range of tissues and present endogenously-derived peptides to cytotoxic T-cells; and non-classical MHC class I genes generally have lower polymorphism, may have tissue-specific expression and have evolved to perform immune-related or non-immune functions. As immune genes can evolve rapidly and are subject to different selection pressure, we hypothesised that there may be divergent, as yet unannotated or uncharacterised class I genes.

Results: Application of a novel method of sensitive genome searching of available vertebrate genome sequences revealed a new, extensive sub-family of divergent MHC class I genes, denoted as UT, which has not previously been characterized. These class I genes are found in both American and Australian marsupials, and in monotremes, at an evolutionary chromosomal breakpoint, but are not present in non-mammalian genomes and have been lost from the eutherian lineage. We show that UT family members are expressed in the thymus of the gray short-tailed opossum and in other immune tissues of several Australian marsupials. Structural homology modelling shows that the proteins encoded by this family are predicted to have an open, though short, antigen-binding groove.

Conclusions: We have identified a novel sub-family of putatively non-classical MHC class I genes that are specific to marsupials and monotremes. This family was present in the ancestral mammal and is found in extant marsupials and monotremes, but has been lost from the eutherian lineage. The function of this family is as yet unknown, however, their predicted structure may be consistent with presentation of antigens to T-cells.

No MeSH data available.