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  • 1
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: Evolution of the two gene families of the complement system involved in the formation of the C3 convertases, B/C2 andC3/C4/C5, was studied at the cDNA level in lower vertebrates. Cyclostomes, the most primitive extant vertebrates, seem to possess only one member each of these families, indicating chat gene duplication between B and C2 or among C3, C4 and C5 occurred in the lineage of jawed vertebrates. Typical C3 and C4 cDNAs were identified in both amphibian (Xenopus) and teleost (medaka fish), locating the C3 /C4 gene duplication before the divergence of ray funned fish and lobe-finned Fish, On the other hand, typical B cDNA was identified in Xenopus, whereas teleost counterparts from three species all showed intermediate character between B and C2, suggesting the possibility that the B/C2 gene duplication occurred in die tetrapod lineage. Genetic linkage between these two family genes within the MHC was observed in Xenopus but not in medaka fish.
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  • 2
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The expression of the fourth component of complement (C4) of the mouse can differ 20-fold and is determined byC4-high (C4 h ) orC4-low (C4 l ) alleles. To investigate the molecular mechanisms underlying the differences in C4 expression, we compared the transcriptional activity of theC4 genes between high and low C4-producer strains of mice (B10 and FM vs B10.BR) using nuclear transcriptional and chloramphenicol acetyltransferase (CAT) assays. We also compared the level of C4-specific RNA in total and nuclear RNA of the liver. The results revealed no significant difference in transcriptional activity betweenC4 h andC4 l genes. However, the steady-state levels of C4 mRNA are ten times lower inC4 l strains than inC4 h strains, suggesting that the major regulation of C4 plasma levels occurs at the post-transcriptional level.
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  • 3
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract ComplementC4 shows extensive structural and functional similarity to complementC3, hence these components are believed to have originated by gene duplication from a common ancestor. Although to dateC3 cDNA clones have been isolated from all major classes of extant vertebrates includingXenopus, C4 cDNA clones have been isolated from mammalian species only. We describe here the molecular cloning and structural analysis ofXenopus C4 cDNA. The cDNA sequence encoding the thioester region ofXenopus C4 was amplified by reverse transcriptase-polymerase chain reaction usingXenopus liver mRNA as a template, and then used to screen a liver cDNA library. The amino acid sequence ofXenopus C4 deduced from a clone containing the entire protein-coding sequence showed 39%, 30%, 25%, and 20% overall identity with those of human C4, C3, C5, and α2-macroglobulin, respectively. The predicted amino acid sequence consisted of a 22-residue putative signal peptide, a 634-residue β chain, a 732-residue α chain, and a 287-residue γ chain. Of 30 cysteine residues, 27 were found in exactly the same positions as in humanC4. Genomic Southern blotting analysis indicated thatC4 is a single copy gene inXenopus and is part of the frog MHC cluster. These results clearly demonstrate thatC3/C4 gene duplication and linkage between theC4 gene and the major histocompatibility complex predate mammalian/amphibian divergence.
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  • 4
    ISSN: 1432-1211
    Keywords: Key words LMP7 ; Trans-species polymorphism ; MHC ; Xenopus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract LMP7 (PSMB8) is a major histocompatibility complex (MHC)-encoded catalytic subunit of 20S immunoproteasome, which is responsible for the production of antigenic peptide to be presented by the MHC class I molecules. Two highly diverged allelic lineages of LMP7, termed LMP7A and LMP7B, have been identified previously in an amphibian, Xenopus laevis. Fourteen Xenopus species were analyzed by genomic Southern hybridization using LMP7A- and LMP7B-specific probes. Ten had both LMP7A and LMP7B, and the other 4 had only LMP7A. Identification of LMP7A and LMP7B was confirmed by reverse transcription-polymerase chain reaction/sequencing analysis of LMP7 mRNA including eight diagnostic amino acid residues that discriminate the two allelic lineages. These data suggest that these two allelic lineages were established more than 80 million years ago, and were transmitted from species to species. Trans-species evolution has so far been reported for MHC class I and II molecules in mammals and teleost fish, and is believed to be a basis for the extraordinary polymorphism of these molecules. A similar mode of evolution of the LMP7 alleles in Xenopus provides a possible explanation for the linkage of the LMP7 gene with the MHC in all vertebrates analyzed to date.
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  • 5
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 6
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have previously reported the molecular cloning of the mammalian major histocompatibility complex (MHC) class III gene, complement factor B (Bf) from Xenopus laevis, and linkage of the gene to the frog MHC. Here, we estimated the copy number of the Xenopus Bf gene by genomic Southern blotting analysis and demonstrated that Xenopus laevis has two copies of the Bf gene. Both genes co-segregated with the MHC-linked HSP70 genes among 19 offspring of an f/r × f/r cross, indicating a close linkage of the two Bf genes to the frog MHC. Both genes are transcribed and contain open reading frames. When compared with the previously determined cDNA sequence (Xenopus Bf A), the predicted amino acid sequence of the second cDNA species (Xenopus Bf B) shows 82% overall identity. Polymerase chain reaction analysis indicated that all of the partially inbred frogs with the f, r, g, and j MHC haplotypes, as well as 12 outbred frogs tested have both Bf genes, suggesting that the duplicated Bf genes are stable genetic traits in Xenopus laevis.
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  • 7
    ISSN: 1432-1211
    Keywords: Key words Complement ; Decay-accelerating factor ; Repetitive sequence ; Gene structure ; Serine/threonine-rich region
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The decay-accelerating factor (DAF, CD55) protects cells from autologous complement attack on self cell membranes. We have previously reported that the seventh exon encoding the serine/threonine-rich(S/T)-abc region of the guinea pig DAF gene is composed of five homologous repeats of about 51 base pairs, and that differential usage of these repeats produces the various lengths observed in the S/T region of guinea pig DAF. In this study, we found that the seventh intron of the guinea pig DAF gene was wholly composed of 18 tandem repeats homologous to the repeating unit of the S/T-abc exon. This type of repetitive structure, although the number of repeats was variable, was also found in the corresponding exons and introns of all DAF genes of other species so far tested including human and seven other primates and mouse, in which alternative splicing in this region has not been found. This suggested that generation of the repetitive sequences spanning the exon and intron regions had occurred before the diversification of these species. In addition, all the intron sequences of the tested DAF genes had no stop codon when they were presumably translated in the same reading frame as the seventh and eighth exons, except for that of one of two duplicated mouse DAF genes. These findings and significant interspecies identities of the intron sequence suggest that the intron sequence conceivably could be translated in some tissues and/or in some stages of development although to date we have not yet succeeded in detecting mRNA for this region.
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Immunological reviews 198 (2004), S. 0 
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary:  Most components of the human complement system have unmistakable domain architectures, making evolutionary tracing feasible. In contrast to the major genes of the adaptive immune system, which are present only in jawed vertebrates, complement component genes with unique domain structures are present not only in jawed vertebrates but also in jawless fish and non-vertebrate deuterostomes. Recent progress in genome analysis in several eukaryotes, occupying the phylogenetically critical positions, showed that most individual domains found in the complement components are metazoa specific, being found both in deuterostomes and in protostomes but not in yeast or plant. However, unique domain architecture of complement components is not present in protostomes, suggesting that the complement system has been established in the deuterostome lineage not by invention of new domains but by innovation of unique combination of the pre-existing domains. The recently assembled Ciona intestinalis draft genome contained the most modular complement genes, except for factor I. However, some possible C. intestinalis complement components show critical structural divergence from the mammalian counterparts, casting doubt on their mutual interaction. Thus, another integrative step seems to have been required to establish the modern complement system of higher vertebrates.
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  • 9
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 10
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary: MHC classical class I and class II genes have been identified in representative species from all major jawed vertebrate taxa, the oldest group being the cartilaginous fish, whereas no class I/II genes of any type have been detected in animals from older taxa. Among ectothermic vertebrate classes, studies of MHC architecture have been done in cartilaginous fish (sharks), bony fish (several teleost species), and amphibians (the frog Xenopus). The Xenopus MHC contains class I, class II, and class III genes, demonstrating that all of these genes were linked in the ancestor of the tetrapods, but the gene order is not the same as that in mouse/man. Studies of poly-ploid Xenopus suggest that MHC genes can be differentially silenced when multiple copies are present; i.e. MHC 'subregions’can be silenced. Surprisingly, in all teleosts examined to date class I and class II genes are not linked. Likewise, class III genes like the complement genes factor B (Bf) and C4 are scattered throughout the genome of teleosts. However, the presumed classical class I genes are closely linked to the‘immune’proteasome genes, LMP2 and LMP7, and to the peptide-transporter genes (TAP), implying that a true‘class I region’exists in this group. A similar type of linkage group is found in chickens and perhaps Xenopus, and thus it may reveal die ancestral organization of class I-associated genes, In cartilaginous fish, classical and non-classical class I genes have been isolated from three shark species, and class II A and B chain genes from nurse sharks. Studies of MHC linkage in sharks are being carried out to provide further understanding of the putative primordial organization of MHC. Segregation studies in one shark family point to linkage of class I and class II genes, suggesting that the non-linkage of these genes in teleosts is a derived characteristic.
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