Limits...
Conservation and divergence of gene families encoding components of innate immune response systems in zebrafish.

Stein C, Caccamo M, Laird G, Leptin M - Genome Biol. (2007)

Bottom Line: Although the genes encoding many components of immune signaling pathways have been found in teleost fish, it is not clear whether all components are present or whether the complexity of the signaling mechanisms employed by mammals is similar in fish.We also found a conserved NACHT-domain protein with WD40 repeats that had previously not been described in mammals.Additionally, we have identified in each of the three fish a large species-specific subgroup of NLR proteins that contain a novel amino-terminal domain that is not found in mammalian genomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genetics, University of Cologne, Zuelpicher Str, 47, 50674 Cologne, Germany. cornelia.stein@uni-koeln.de

ABSTRACT

Background: The zebrafish has become a widely used model to study disease resistance and immunity. Although the genes encoding many components of immune signaling pathways have been found in teleost fish, it is not clear whether all components are present or whether the complexity of the signaling mechanisms employed by mammals is similar in fish.

Results: We searched the genomes of the zebrafish Danio rerio and two pufferfish for genes encoding components of the Toll-like receptor and interferon signaling pathways, the NLR (NACHT-domain and leucine rich repeat containing) protein family, and related proteins. We find that most of the components known in mammals are also present in fish, with clearly recognizable orthologous relationships. The class II cytokines and their receptors have diverged extensively, obscuring orthologies, but the number of receptors is similar in all species analyzed. In the family of the NLR proteins, the canonical members are conserved. We also found a conserved NACHT-domain protein with WD40 repeats that had previously not been described in mammals. Additionally, we have identified in each of the three fish a large species-specific subgroup of NLR proteins that contain a novel amino-terminal domain that is not found in mammalian genomes.

Conclusion: The main innate immune signaling pathways are conserved in mammals and teleost fish. Whereas the components that act downstream of the receptors are highly conserved, with orthologous sets of genes in mammals and teleosts, components that are known or assumed to interact with pathogens are more divergent and have undergone lineage-specific expansions.

Show MeSH

Related in: MedlinePlus

Genomic organization of two class II cytokine gene clusters. Chromosomes are shown as lines with the positions of the region marked in megabase pairs underneath. Genes transcribed on the top strand are shown above the line, and those transcribed in the opposite direction are shown below. Class II cytokine encoding genes are shaded in gray. In the left diagram the syntenic regions and duplications, and inversions surrounding the IL-10 locus are shaded in red and blue. The human IL-10 gene is located on chromosome 1 and the region shows the same arrangement as in the mouse. The current zebrafish genome assembly Zv7 does not yet contain the recently sequenced clone CU459075, which places IL-34 into the interval between IL-10 and prolargin (IL-34 is included in Zv7 on the unplaced contig Zv7_NA1656). There are therefore no coordinates for the right end of the interval. The two pufferfish show the same arrangement both for the region around IL-10 and for the MDM1/cytokine/IFN-γ region. The names for the fish genes are explained in the text. IFN, interferon; IL, interleukin.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2258186&req=5

Figure 11: Genomic organization of two class II cytokine gene clusters. Chromosomes are shown as lines with the positions of the region marked in megabase pairs underneath. Genes transcribed on the top strand are shown above the line, and those transcribed in the opposite direction are shown below. Class II cytokine encoding genes are shaded in gray. In the left diagram the syntenic regions and duplications, and inversions surrounding the IL-10 locus are shaded in red and blue. The human IL-10 gene is located on chromosome 1 and the region shows the same arrangement as in the mouse. The current zebrafish genome assembly Zv7 does not yet contain the recently sequenced clone CU459075, which places IL-34 into the interval between IL-10 and prolargin (IL-34 is included in Zv7 on the unplaced contig Zv7_NA1656). There are therefore no coordinates for the right end of the interval. The two pufferfish show the same arrangement both for the region around IL-10 and for the MDM1/cytokine/IFN-γ region. The names for the fish genes are explained in the text. IFN, interferon; IL, interleukin.

Mentions: Among these class II cytokines, IL-10 exhibits an apparent orthology between fish and mammals [41,42]. This is also supported by the genomic locations of the IL-10 genes, which are situated adjacent to and on the opposite strand of the Mapkap2 genes in all five species (Figure 11). The genes that had been annotated as IL-20 in the zebrafish (Refseq: NP_001076424.1) and Tetraodon (Uniprot: Q7SX60), and initially as IL-19 and then changed to IL-24 in Takifugu (Ensembl: SINFRUG00000154816) are equally related to mammalian IL-19 and IL-20. The previous automated naming of the fish genes should therefore be amended. In concordance with the nomenclature rules for vertebrate gene families, this gene has therefore been given the next available number in the IL series (IL-34). The fish IL-34 genes and the mammalian IL-19, IL-20, and IL-24 genes are located in the vicinity of the IL-10 genes (in the zebrafish this gene has not yet been placed on a chromosome), but duplications and inversions have broken up the syntenic relationships downstream of IL-10. The phylogenetic tree argues for a common precursor for these genes that has duplicated in mammals, yielding IL-19 and IL-20. Whether IL-24 is the product of a second local duplication or of an older duplication of a larger segment of the genome is not clear, but it shows a higher degree of similarity to the class II cytokine genes found in a complex on a different chromosome in all five species (Figure 11).


Conservation and divergence of gene families encoding components of innate immune response systems in zebrafish.

Stein C, Caccamo M, Laird G, Leptin M - Genome Biol. (2007)

Genomic organization of two class II cytokine gene clusters. Chromosomes are shown as lines with the positions of the region marked in megabase pairs underneath. Genes transcribed on the top strand are shown above the line, and those transcribed in the opposite direction are shown below. Class II cytokine encoding genes are shaded in gray. In the left diagram the syntenic regions and duplications, and inversions surrounding the IL-10 locus are shaded in red and blue. The human IL-10 gene is located on chromosome 1 and the region shows the same arrangement as in the mouse. The current zebrafish genome assembly Zv7 does not yet contain the recently sequenced clone CU459075, which places IL-34 into the interval between IL-10 and prolargin (IL-34 is included in Zv7 on the unplaced contig Zv7_NA1656). There are therefore no coordinates for the right end of the interval. The two pufferfish show the same arrangement both for the region around IL-10 and for the MDM1/cytokine/IFN-γ region. The names for the fish genes are explained in the text. IFN, interferon; IL, interleukin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2258186&req=5

Figure 11: Genomic organization of two class II cytokine gene clusters. Chromosomes are shown as lines with the positions of the region marked in megabase pairs underneath. Genes transcribed on the top strand are shown above the line, and those transcribed in the opposite direction are shown below. Class II cytokine encoding genes are shaded in gray. In the left diagram the syntenic regions and duplications, and inversions surrounding the IL-10 locus are shaded in red and blue. The human IL-10 gene is located on chromosome 1 and the region shows the same arrangement as in the mouse. The current zebrafish genome assembly Zv7 does not yet contain the recently sequenced clone CU459075, which places IL-34 into the interval between IL-10 and prolargin (IL-34 is included in Zv7 on the unplaced contig Zv7_NA1656). There are therefore no coordinates for the right end of the interval. The two pufferfish show the same arrangement both for the region around IL-10 and for the MDM1/cytokine/IFN-γ region. The names for the fish genes are explained in the text. IFN, interferon; IL, interleukin.
Mentions: Among these class II cytokines, IL-10 exhibits an apparent orthology between fish and mammals [41,42]. This is also supported by the genomic locations of the IL-10 genes, which are situated adjacent to and on the opposite strand of the Mapkap2 genes in all five species (Figure 11). The genes that had been annotated as IL-20 in the zebrafish (Refseq: NP_001076424.1) and Tetraodon (Uniprot: Q7SX60), and initially as IL-19 and then changed to IL-24 in Takifugu (Ensembl: SINFRUG00000154816) are equally related to mammalian IL-19 and IL-20. The previous automated naming of the fish genes should therefore be amended. In concordance with the nomenclature rules for vertebrate gene families, this gene has therefore been given the next available number in the IL series (IL-34). The fish IL-34 genes and the mammalian IL-19, IL-20, and IL-24 genes are located in the vicinity of the IL-10 genes (in the zebrafish this gene has not yet been placed on a chromosome), but duplications and inversions have broken up the syntenic relationships downstream of IL-10. The phylogenetic tree argues for a common precursor for these genes that has duplicated in mammals, yielding IL-19 and IL-20. Whether IL-24 is the product of a second local duplication or of an older duplication of a larger segment of the genome is not clear, but it shows a higher degree of similarity to the class II cytokine genes found in a complex on a different chromosome in all five species (Figure 11).

Bottom Line: Although the genes encoding many components of immune signaling pathways have been found in teleost fish, it is not clear whether all components are present or whether the complexity of the signaling mechanisms employed by mammals is similar in fish.We also found a conserved NACHT-domain protein with WD40 repeats that had previously not been described in mammals.Additionally, we have identified in each of the three fish a large species-specific subgroup of NLR proteins that contain a novel amino-terminal domain that is not found in mammalian genomes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genetics, University of Cologne, Zuelpicher Str, 47, 50674 Cologne, Germany. cornelia.stein@uni-koeln.de

ABSTRACT

Background: The zebrafish has become a widely used model to study disease resistance and immunity. Although the genes encoding many components of immune signaling pathways have been found in teleost fish, it is not clear whether all components are present or whether the complexity of the signaling mechanisms employed by mammals is similar in fish.

Results: We searched the genomes of the zebrafish Danio rerio and two pufferfish for genes encoding components of the Toll-like receptor and interferon signaling pathways, the NLR (NACHT-domain and leucine rich repeat containing) protein family, and related proteins. We find that most of the components known in mammals are also present in fish, with clearly recognizable orthologous relationships. The class II cytokines and their receptors have diverged extensively, obscuring orthologies, but the number of receptors is similar in all species analyzed. In the family of the NLR proteins, the canonical members are conserved. We also found a conserved NACHT-domain protein with WD40 repeats that had previously not been described in mammals. Additionally, we have identified in each of the three fish a large species-specific subgroup of NLR proteins that contain a novel amino-terminal domain that is not found in mammalian genomes.

Conclusion: The main innate immune signaling pathways are conserved in mammals and teleost fish. Whereas the components that act downstream of the receptors are highly conserved, with orthologous sets of genes in mammals and teleosts, components that are known or assumed to interact with pathogens are more divergent and have undergone lineage-specific expansions.

Show MeSH
Related in: MedlinePlus