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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

Phylogenetic tree of MHC class II α1 domain sequences. The sequences which possess αW43 are labeled with the orange letter “W”. The bootstrap consensus tree was inferred from 500 replicates using the Neighbor-Joining method [61]. The tree is drawn to scale, with branch lengths representing the number of amino acid substitutions per site (see scale bar). Numbers behind names relate to references listed in Additional file 10: Text S4. Sequences that are also depicted in Figure 2 have their names with colored shapes indicative for the species: black square for spotted gar, red circle for Atlantic salmon, green circle for zebrafish, purple square for medaka, violet triangle for stickleback, gray diamond for Tetraodon, teal triangle for Fugu, blue diamond for Nile tilapia. Identical shapes, but white, are used for other reported sequences of those species. DM sequences are shown with the yellow background color. Tetrapod classical (-related) sequences are shown with the orange background color. The other background colors distinguish DA, DB and DE sequences, and within the DA group also cyprinid, salmonid and neoteleost sequences are distinguished. The dashed blue line divides the DA/DB lineage from the other class II sequences. S1, S2 and S3 indications plus dashed lines refer to products of genes situated in the respective synteny regions (Figure 2). Spotted gar 501A1 shows some interesting similarity with MHC class II of other classes of vertebrates (see also Additional file 10: Text S4 and Additional file 3: Figure S3B), but this single sequence does not provide sufficient information for valid discussion.
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Figure 4: Phylogenetic tree of MHC class II α1 domain sequences. The sequences which possess αW43 are labeled with the orange letter “W”. The bootstrap consensus tree was inferred from 500 replicates using the Neighbor-Joining method [61]. The tree is drawn to scale, with branch lengths representing the number of amino acid substitutions per site (see scale bar). Numbers behind names relate to references listed in Additional file 10: Text S4. Sequences that are also depicted in Figure 2 have their names with colored shapes indicative for the species: black square for spotted gar, red circle for Atlantic salmon, green circle for zebrafish, purple square for medaka, violet triangle for stickleback, gray diamond for Tetraodon, teal triangle for Fugu, blue diamond for Nile tilapia. Identical shapes, but white, are used for other reported sequences of those species. DM sequences are shown with the yellow background color. Tetrapod classical (-related) sequences are shown with the orange background color. The other background colors distinguish DA, DB and DE sequences, and within the DA group also cyprinid, salmonid and neoteleost sequences are distinguished. The dashed blue line divides the DA/DB lineage from the other class II sequences. S1, S2 and S3 indications plus dashed lines refer to products of genes situated in the respective synteny regions (Figure 2). Spotted gar 501A1 shows some interesting similarity with MHC class II of other classes of vertebrates (see also Additional file 10: Text S4 and Additional file 3: Figure S3B), but this single sequence does not provide sufficient information for valid discussion.

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)

Phylogenetic tree of MHC class II α1 domain sequences. The sequences which possess αW43 are labeled with the orange letter “W”. The bootstrap consensus tree was inferred from 500 replicates using the Neighbor-Joining method [61]. The tree is drawn to scale, with branch lengths representing the number of amino acid substitutions per site (see scale bar). Numbers behind names relate to references listed in Additional file 10: Text S4. Sequences that are also depicted in Figure 2 have their names with colored shapes indicative for the species: black square for spotted gar, red circle for Atlantic salmon, green circle for zebrafish, purple square for medaka, violet triangle for stickleback, gray diamond for Tetraodon, teal triangle for Fugu, blue diamond for Nile tilapia. Identical shapes, but white, are used for other reported sequences of those species. DM sequences are shown with the yellow background color. Tetrapod classical (-related) sequences are shown with the orange background color. The other background colors distinguish DA, DB and DE sequences, and within the DA group also cyprinid, salmonid and neoteleost sequences are distinguished. The dashed blue line divides the DA/DB lineage from the other class II sequences. S1, S2 and S3 indications plus dashed lines refer to products of genes situated in the respective synteny regions (Figure 2). Spotted gar 501A1 shows some interesting similarity with MHC class II of other classes of vertebrates (see also Additional file 10: Text S4 and Additional file 3: Figure S3B), but this single sequence does not provide sufficient information for valid discussion.
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Related In: Results  -  Collection

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Figure 4: Phylogenetic tree of MHC class II α1 domain sequences. The sequences which possess αW43 are labeled with the orange letter “W”. The bootstrap consensus tree was inferred from 500 replicates using the Neighbor-Joining method [61]. The tree is drawn to scale, with branch lengths representing the number of amino acid substitutions per site (see scale bar). Numbers behind names relate to references listed in Additional file 10: Text S4. Sequences that are also depicted in Figure 2 have their names with colored shapes indicative for the species: black square for spotted gar, red circle for Atlantic salmon, green circle for zebrafish, purple square for medaka, violet triangle for stickleback, gray diamond for Tetraodon, teal triangle for Fugu, blue diamond for Nile tilapia. Identical shapes, but white, are used for other reported sequences of those species. DM sequences are shown with the yellow background color. Tetrapod classical (-related) sequences are shown with the orange background color. The other background colors distinguish DA, DB and DE sequences, and within the DA group also cyprinid, salmonid and neoteleost sequences are distinguished. The dashed blue line divides the DA/DB lineage from the other class II sequences. S1, S2 and S3 indications plus dashed lines refer to products of genes situated in the respective synteny regions (Figure 2). Spotted gar 501A1 shows some interesting similarity with MHC class II of other classes of vertebrates (see also Additional file 10: Text S4 and Additional file 3: Figure S3B), but this single sequence does not provide sufficient information for valid discussion.
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