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Comprehensive analysis of MHC class II genes in teleost fish genomes reveals dispensability of the peptide-loading DM system in a large part of vertebrates.

Dijkstra JM, Grimholt U, Leong J, Koop BF, Hashimoto K - BMC Evol. Biol. (2013)

Bottom Line: Although the absence of DM-like genes in teleost fish has been speculated based on the results of homology searches, it has not been definitively clear whether the DM system is truly specific for tetrapods or not.We discovered a novel ancient class II group (DE) in teleost fish and classified teleost fish class II genes into three major groups (DA, DB and DE).Analyses of predicted class II molecules revealed that the critical tryptophan residue required for a classical class II molecule in the DM system could be found only in some non-classical but not in classical-type class II molecules of teleost fish.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan. unni.grimholt@ibv.uio.no.

ABSTRACT

Background: Classical major histocompatibility complex (MHC) class II molecules play an essential role in presenting peptide antigens to CD4+ T lymphocytes in the acquired immune system. The non-classical class II DM molecule, HLA-DM in the case of humans, possesses critical function in assisting the classical MHC class II molecules for proper peptide loading and is highly conserved in tetrapod species. Although the absence of DM-like genes in teleost fish has been speculated based on the results of homology searches, it has not been definitively clear whether the DM system is truly specific for tetrapods or not. To obtain a clear answer, we comprehensively searched class II genes in representative teleost fish genomes and analyzed those genes regarding the critical functional features required for the DM system.

Results: We discovered a novel ancient class II group (DE) in teleost fish and classified teleost fish class II genes into three major groups (DA, DB and DE). Based on several criteria, we investigated the classical/non-classical nature of various class II genes and showed that only one of three groups (DA) exhibits classical-type characteristics. Analyses of predicted class II molecules revealed that the critical tryptophan residue required for a classical class II molecule in the DM system could be found only in some non-classical but not in classical-type class II molecules of teleost fish.

Conclusions: Teleost fish, a major group of vertebrates, do not possess the DM system for the classical class II peptide-loading and this sophisticated system has specially evolved in the tetrapod lineage.

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Related in: MedlinePlus

MHC class II loci in gar and various teleost fish. Schematic view of MHC class II A and B genomic regions as found for gar (A), salmon and zebrafish (B), and neoteleosts (C), and, for the teleost fishes, organized per DE, DB and DA group. Small blocks indicate genes, and stars indicate ends of scaffolds. Nomenclature and gene identities are explained in Additional file 2: Figure S2, and for salmon also in Additional file 8: Text S2. Synteny with class II genomic regions in other species is indicated by similar coloring of homologues: blue for Mhc-scaffold genes as found in human, dark green for neoteleost S1 region genes, lime green for neoteleost S2 region genes, and purple for neoteleost S3 region genes. Dotted and dashed purple lines indicate extended and probable S3 regions, respectively. Orange and red boxes represent MHC class II and MHC class I genes, respectively. “A” stands for a class II α chain gene and “B” for a β chain gene. Class II A and B gene names are in red font if matching transcripts were found (Additional file 5: Table S2 and Additional file 7: Text S1), and the name is boxed if matching transcripts were abundant. Crosses indicate pseudogenes and/or genes with incomplete information. White backgrounds indicate that in syntenic regions in other species also MHC class II genes were found, blue backgrounds indicate scaffolds without such class II synteny, and gray backgrounds indicate lack of sufficient sequence information for estimation of synteny. Observed synteny between teleost regions regardless of MHC class II presence (Additional file 4: Table S1) is summarized behind scaffolds by “M + number” and “D + number” for the respective chromosome numbers in medaka (M) and zebrafish (D for Danio), respectively. Linkage of classical-type class I and class II in spotted gar scaffold 501 suggests that this is an Mhc region, but more information on neighboring genes is needed (therefore dashed blue line). MHC class I genes on zebrafish Chr.8 are nonclassical [56]. The MHC class II genes and the Mhc-scaffold gene MSH5 (Additional file 2: Figure S2) in the neoteleost S1 group may or may not have derived from a direct translocation from the Mhc region on the same chromosome [33]. Tetraodon scaffold T55 has no synteny with regions in other species (Additional file 7: Table S1), so the linkage of T55 A gene with Mhc-scaffold genes (Additional file 2: Figure S2) is probably not ancestral. a Eight tilapia regions with little informative value were omitted from the figure, but are shown in Additional file 2: Figure S2.
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Figure 2: MHC class II loci in gar and various teleost fish. Schematic view of MHC class II A and B genomic regions as found for gar (A), salmon and zebrafish (B), and neoteleosts (C), and, for the teleost fishes, organized per DE, DB and DA group. Small blocks indicate genes, and stars indicate ends of scaffolds. Nomenclature and gene identities are explained in Additional file 2: Figure S2, and for salmon also in Additional file 8: Text S2. Synteny with class II genomic regions in other species is indicated by similar coloring of homologues: blue for Mhc-scaffold genes as found in human, dark green for neoteleost S1 region genes, lime green for neoteleost S2 region genes, and purple for neoteleost S3 region genes. Dotted and dashed purple lines indicate extended and probable S3 regions, respectively. Orange and red boxes represent MHC class II and MHC class I genes, respectively. “A” stands for a class II α chain gene and “B” for a β chain gene. Class II A and B gene names are in red font if matching transcripts were found (Additional file 5: Table S2 and Additional file 7: Text S1), and the name is boxed if matching transcripts were abundant. Crosses indicate pseudogenes and/or genes with incomplete information. White backgrounds indicate that in syntenic regions in other species also MHC class II genes were found, blue backgrounds indicate scaffolds without such class II synteny, and gray backgrounds indicate lack of sufficient sequence information for estimation of synteny. Observed synteny between teleost regions regardless of MHC class II presence (Additional file 4: Table S1) is summarized behind scaffolds by “M + number” and “D + number” for the respective chromosome numbers in medaka (M) and zebrafish (D for Danio), respectively. Linkage of classical-type class I and class II in spotted gar scaffold 501 suggests that this is an Mhc region, but more information on neighboring genes is needed (therefore dashed blue line). MHC class I genes on zebrafish Chr.8 are nonclassical [56]. The MHC class II genes and the Mhc-scaffold gene MSH5 (Additional file 2: Figure S2) in the neoteleost S1 group may or may not have derived from a direct translocation from the Mhc region on the same chromosome [33]. Tetraodon scaffold T55 has no synteny with regions in other species (Additional file 7: Table S1), so the linkage of T55 A gene with Mhc-scaffold genes (Additional file 2: Figure S2) is probably not ancestral. a Eight tilapia regions with little informative value were omitted from the figure, but are shown in Additional file 2: Figure S2.

Mentions: Using various databases, we extensively searched for teleost MHC class II genes. The ancestors of teleost fish and tetrapods have separated from each other more than 400 million years ago (Figure 1). Evolutionary relationships among relevant species are depicted in Figure 1 and also in Additional file 1: Figure S1, with more details. We identified a total of 120 MHC class II genes or partial genes in the following Ensembl genomic databases: Danio rerio (zebrafish; ZV9), Gasterosteus aculeatus (stickleback; BROAD S1), Oryzias latipes (Medaka1), Takifugu rubripes (Fugu4.0), Tetraodon nigroviridis (Tetraodon8.0) and Oreochromis niloticus (Nile tilapia; Orenil 1.0). Seventy-eight of these sequences are devoid of apparent deletions, premature stop codons and/or frame-shifts. Further, we investigated our improved assembly of the Atlantic salmon genome and found five new class II genes. The MHC class II sequences obtained in this study are summarized in Figure 2 (their genomic locations with surrounding genes). The amino acid sequence comparison of representative class II sequences is presented in Figure 3. The phylogenetic tree analyzed based on the aligned sequences is shown in Figure 4 (α1 domain of class II α chain) as a representative. Additional file 2: Figure S2, Additional file 3: Figure S3, Additional file 4: Table S1, Additional file 5: Table S2, Additional file 6: Table S3, Additional file 7: Text S1, Additional file 8: Text S2, Additional file 9: Text S3 and Additional file 10: Text S4 provide the detailed information.


Comprehensive analysis of MHC class II genes in teleost fish genomes reveals dispensability of the peptide-loading DM system in a large part of vertebrates.

Dijkstra JM, Grimholt U, Leong J, Koop BF, Hashimoto K - BMC Evol. Biol. (2013)

MHC class II loci in gar and various teleost fish. Schematic view of MHC class II A and B genomic regions as found for gar (A), salmon and zebrafish (B), and neoteleosts (C), and, for the teleost fishes, organized per DE, DB and DA group. Small blocks indicate genes, and stars indicate ends of scaffolds. Nomenclature and gene identities are explained in Additional file 2: Figure S2, and for salmon also in Additional file 8: Text S2. Synteny with class II genomic regions in other species is indicated by similar coloring of homologues: blue for Mhc-scaffold genes as found in human, dark green for neoteleost S1 region genes, lime green for neoteleost S2 region genes, and purple for neoteleost S3 region genes. Dotted and dashed purple lines indicate extended and probable S3 regions, respectively. Orange and red boxes represent MHC class II and MHC class I genes, respectively. “A” stands for a class II α chain gene and “B” for a β chain gene. Class II A and B gene names are in red font if matching transcripts were found (Additional file 5: Table S2 and Additional file 7: Text S1), and the name is boxed if matching transcripts were abundant. Crosses indicate pseudogenes and/or genes with incomplete information. White backgrounds indicate that in syntenic regions in other species also MHC class II genes were found, blue backgrounds indicate scaffolds without such class II synteny, and gray backgrounds indicate lack of sufficient sequence information for estimation of synteny. Observed synteny between teleost regions regardless of MHC class II presence (Additional file 4: Table S1) is summarized behind scaffolds by “M + number” and “D + number” for the respective chromosome numbers in medaka (M) and zebrafish (D for Danio), respectively. Linkage of classical-type class I and class II in spotted gar scaffold 501 suggests that this is an Mhc region, but more information on neighboring genes is needed (therefore dashed blue line). MHC class I genes on zebrafish Chr.8 are nonclassical [56]. The MHC class II genes and the Mhc-scaffold gene MSH5 (Additional file 2: Figure S2) in the neoteleost S1 group may or may not have derived from a direct translocation from the Mhc region on the same chromosome [33]. Tetraodon scaffold T55 has no synteny with regions in other species (Additional file 7: Table S1), so the linkage of T55 A gene with Mhc-scaffold genes (Additional file 2: Figure S2) is probably not ancestral. a Eight tilapia regions with little informative value were omitted from the figure, but are shown in Additional file 2: Figure S2.
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Figure 2: MHC class II loci in gar and various teleost fish. Schematic view of MHC class II A and B genomic regions as found for gar (A), salmon and zebrafish (B), and neoteleosts (C), and, for the teleost fishes, organized per DE, DB and DA group. Small blocks indicate genes, and stars indicate ends of scaffolds. Nomenclature and gene identities are explained in Additional file 2: Figure S2, and for salmon also in Additional file 8: Text S2. Synteny with class II genomic regions in other species is indicated by similar coloring of homologues: blue for Mhc-scaffold genes as found in human, dark green for neoteleost S1 region genes, lime green for neoteleost S2 region genes, and purple for neoteleost S3 region genes. Dotted and dashed purple lines indicate extended and probable S3 regions, respectively. Orange and red boxes represent MHC class II and MHC class I genes, respectively. “A” stands for a class II α chain gene and “B” for a β chain gene. Class II A and B gene names are in red font if matching transcripts were found (Additional file 5: Table S2 and Additional file 7: Text S1), and the name is boxed if matching transcripts were abundant. Crosses indicate pseudogenes and/or genes with incomplete information. White backgrounds indicate that in syntenic regions in other species also MHC class II genes were found, blue backgrounds indicate scaffolds without such class II synteny, and gray backgrounds indicate lack of sufficient sequence information for estimation of synteny. Observed synteny between teleost regions regardless of MHC class II presence (Additional file 4: Table S1) is summarized behind scaffolds by “M + number” and “D + number” for the respective chromosome numbers in medaka (M) and zebrafish (D for Danio), respectively. Linkage of classical-type class I and class II in spotted gar scaffold 501 suggests that this is an Mhc region, but more information on neighboring genes is needed (therefore dashed blue line). MHC class I genes on zebrafish Chr.8 are nonclassical [56]. The MHC class II genes and the Mhc-scaffold gene MSH5 (Additional file 2: Figure S2) in the neoteleost S1 group may or may not have derived from a direct translocation from the Mhc region on the same chromosome [33]. Tetraodon scaffold T55 has no synteny with regions in other species (Additional file 7: Table S1), so the linkage of T55 A gene with Mhc-scaffold genes (Additional file 2: Figure S2) is probably not ancestral. a Eight tilapia regions with little informative value were omitted from the figure, but are shown in Additional file 2: Figure S2.
Mentions: Using various databases, we extensively searched for teleost MHC class II genes. The ancestors of teleost fish and tetrapods have separated from each other more than 400 million years ago (Figure 1). Evolutionary relationships among relevant species are depicted in Figure 1 and also in Additional file 1: Figure S1, with more details. We identified a total of 120 MHC class II genes or partial genes in the following Ensembl genomic databases: Danio rerio (zebrafish; ZV9), Gasterosteus aculeatus (stickleback; BROAD S1), Oryzias latipes (Medaka1), Takifugu rubripes (Fugu4.0), Tetraodon nigroviridis (Tetraodon8.0) and Oreochromis niloticus (Nile tilapia; Orenil 1.0). Seventy-eight of these sequences are devoid of apparent deletions, premature stop codons and/or frame-shifts. Further, we investigated our improved assembly of the Atlantic salmon genome and found five new class II genes. The MHC class II sequences obtained in this study are summarized in Figure 2 (their genomic locations with surrounding genes). The amino acid sequence comparison of representative class II sequences is presented in Figure 3. The phylogenetic tree analyzed based on the aligned sequences is shown in Figure 4 (α1 domain of class II α chain) as a representative. Additional file 2: Figure S2, Additional file 3: Figure S3, Additional file 4: Table S1, Additional file 5: Table S2, Additional file 6: Table S3, Additional file 7: Text S1, Additional file 8: Text S2, Additional file 9: Text S3 and Additional file 10: Text S4 provide the detailed information.

Bottom Line: Although the absence of DM-like genes in teleost fish has been speculated based on the results of homology searches, it has not been definitively clear whether the DM system is truly specific for tetrapods or not.We discovered a novel ancient class II group (DE) in teleost fish and classified teleost fish class II genes into three major groups (DA, DB and DE).Analyses of predicted class II molecules revealed that the critical tryptophan residue required for a classical class II molecule in the DM system could be found only in some non-classical but not in classical-type class II molecules of teleost fish.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan. unni.grimholt@ibv.uio.no.

ABSTRACT

Background: Classical major histocompatibility complex (MHC) class II molecules play an essential role in presenting peptide antigens to CD4+ T lymphocytes in the acquired immune system. The non-classical class II DM molecule, HLA-DM in the case of humans, possesses critical function in assisting the classical MHC class II molecules for proper peptide loading and is highly conserved in tetrapod species. Although the absence of DM-like genes in teleost fish has been speculated based on the results of homology searches, it has not been definitively clear whether the DM system is truly specific for tetrapods or not. To obtain a clear answer, we comprehensively searched class II genes in representative teleost fish genomes and analyzed those genes regarding the critical functional features required for the DM system.

Results: We discovered a novel ancient class II group (DE) in teleost fish and classified teleost fish class II genes into three major groups (DA, DB and DE). Based on several criteria, we investigated the classical/non-classical nature of various class II genes and showed that only one of three groups (DA) exhibits classical-type characteristics. Analyses of predicted class II molecules revealed that the critical tryptophan residue required for a classical class II molecule in the DM system could be found only in some non-classical but not in classical-type class II molecules of teleost fish.

Conclusions: Teleost fish, a major group of vertebrates, do not possess the DM system for the classical class II peptide-loading and this sophisticated system has specially evolved in the tetrapod lineage.

Show MeSH
Related in: MedlinePlus