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1.
Sequence of a human immunoglobulin gamma 3 heavy chain constant region gene: comparison with the other human C gamma genes. 总被引:13,自引:2,他引:11 下载免费PDF全文
We report the first and complete nucleotide sequence of a human gamma 3 heavy chain constant region gene (C gamma 3). This gene displays the same organization than the others C gamma genes and exhibits normal RNA splice and polyadenylation sites. A comparison of its primary sequence with those of C gamma 1, C gamma 2 and C gamma 4 genes confirms the high degree of homology (95%) of the human family in both coding and non-coding regions, and the divergence of the hinge region. The C gamma 3 gene we sequenced codes for a Gm(b) gamma 3 chain (EZZ). Comparison with other known protein sequences reveals that only two specific aminoacids are involved in the Gm(b) and Gm(g) allotypes, which suggests an important part of the spatial configuration in the allotypic specificities. 相似文献
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Structure of human immunoglobulin gamma genes: implications for evolution of a gene family 总被引:32,自引:0,他引:32
We have cloned five human immunoglobulin gamma genes from a fetal liver gene library. Four of them encode the known human immunoglobulin gamma chains gamma 1, gamma 2, gamma 3 and gamma 4. A fifth gamma gene seems to be a pseudogene. Nucleotide sequence determination demonstrates that the gamma 3 gene contains four separate hinge exons. Comparison of these hinge exons with those of the other gamma genes indicates that the first hinge exon is homologous to that of the pseudogene, and that the other three hinge exons are homologous to that of the gamma 1 gene, suggesting that the gamma 3 gene ancestor is a hybrid gene created by unequal crossing-over between the ancestral gamma 1 and psi gamma genes. Amplification of the gamma 1-type hinge exon probably followed to complete the gamma 3 gene. This hypothesis inevitably postulates the gene order 5'-gamma 1-gamma 3-psi gamma-3'. Cloning of overlapping chromosomal segments demonstrates that the gamma 2 gene is located 19 kb 5' to the gamma 4 gene. These analyses indicate that the human gamma-gene family has evolved by several types of DNA rearrangemet, including duplication of a complete gene; duplication of a hinge exon; and reassortment of exons by unequal cross-over between two adjacent genes. 相似文献
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R P Woychik S A Camper R H Lyons S Horowitz E C Goodwin F M Rottman 《Nucleic acids research》1982,10(22):7197-7210
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The hinge region of the immunoglobulin molecule is responsible for antigen-binding and cross-linking reactions, varying the distance between the two antigen-binding sites. As the amino acid sequence of the hinge region is identical among immunoglobulin molecules of the same (sub)class, it has been regarded as a constant region. By comparison of the nucleotide sequences among primate C alpha genes, it is clear that there is a wide variety of length among the hinge regions of hominoid C alpha genes, which basically consist of tandem repeats of a 15 base-pair sequence. This reiterated structure probably facilitates rapid evolutionary changes in the length of the hinge region. The hinge region of the Old World monkey C alpha gene has a non-reiterated structure whose nucleotide sequence is quite different from those of the hominoid C alpha genes, although its surrounding region is conserved during evolution. This unusual hypervariability reveals that the hinge region has evolved as a semi-variable region in contrast to its constant character from an ontogenic viewpoint. 相似文献
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Nucleotide sequences of switch regions of immunoglobulin C epsilon and C gamma genes and their comparison 总被引:24,自引:0,他引:24
Immunoglobulin class switch involves a unique recombination event that takes place at the switch (S) region which is located 5' to each constant region (C) gene of the heavy (H) chain. For example, differentiation of the B lymphocyte from a mu-chain producer to an epsilon-chain producer is mediated by the switch recombination between the S mu and S epsilon regions. In order to elucidate the molecular mechanism for the switch recombination, we have determined nucleotide sequences surrounding the class switch recombination sites of the C epsilon and C gamma 3 genes and those in the 5' flanking regions of the C gamma 2a and C delta genes. The results indicate that the 5' flanking regions of all the CH genes except for the C delta gene contain the S regions which comprise tandem repetition of short unit sequences in agreement with the previous analyses of the S gamma 1, S gamma 2b, S mu, and S alpha regions. Comparison of the nucleotide sequences of all the S regions revealed that length as well as nucleotide sequences of the S regions vary among different classes of the CH gene, but they share short common sequences, (G)AGCT and TGGG(G). The nucleotide sequence of the S mu region is homologous to those of the other S regions in the decreasing order of the S epsilon, S alpha, S gamma 3, and (S gamma 1, S gamma 2b, s gamma 2a) regions. We have compared the nucleotide sequences immediately adjacent to the recombination sites of seven rearranged genes and have always fund tetranucleotides TGAG and/or TGGG, except for one case. Such tetranucleotides may constitute a part of the recognition sequence of a putative recombinase. These results provide further support for our previous proposal that the switch recombination may be facilitated by short common sequences dispersed in all the S regions. 相似文献
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Cloning and complete nucleotide sequence of mouse immunoglobulin gamma 1 chain gene. 总被引:65,自引:0,他引:65
The 6.6 kb DNA fragment coding for the immunoglobulin γ1 chain was cloned from newborn mouse DNA using λgtWES·λB as the EK2 vector. The complete nucleotide sequence (1823 bases) of the γ1 chain gene was determined. The cloned gene contained the entire constant region gene sequence as well as the poly(A) addition site, but not the variable region gene. The results indicate that the variable and constant region genes of immunoglobulin heavy chain are separated in newborn mouse DNA. The constant region genes of other gamma chains (that is, γ2a, γ2b and γ3) are not present in the cloned DNA fragment. The sequence demonstrates that the γ1 chain gene is interrupted by three intervening sequences at the junction of the domains and the hinge region, as previously shown in the γ2b and α chain genes and in the γ1 chain gene cloned from myeloma. The results suggest that the intervening sequence was introduced into the heavy chain gene before divergence of the heavy chain classes, and also support the hypothesis that the splicing mechanism has facilitated the evolution of eucaryotic genes by linking duplicated domains or prototype peptides not directly adjacent to one another. Comparison of the nucleotide sequence of the γ1 chain gene around the boundaries of the coding and intervening sequences with those of other mouse genes revealed extensive divergence, although short prevalent sequences of AG-GTCAG at the 5′ border of the intervening sequence and TCTGCAG-GC at the 3′ border were deduced. A limited homology of nucleotide sequences was found among domains and between the hinge region and the 5′ portion of the CH2 domain. Comparison of 3′ untranslated sequences from the γ1 and γ2b chain genes and the mouse major β-globin gene shows significant homology and a palindrome sequence surrounding the poly(A) addition site. 相似文献
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Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution 总被引:5,自引:0,他引:5
The fetal globin genes G gamma and A gamma from one chromosome of a
chimpanzee (Pan troglodytes) were sequenced and found to be closely similar
to the corresponding genes of man and the gorilla. These genes contain
identical promoter and termination signals and have exons 1 and 2 separated
by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the
more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G
gamma and A gamma, respectively). Each intron 2 has a stretch of simple
sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The
two chimpanzee genes encode polypeptide chains that differ only at position
136 (glycine in G gamma and alanine in A gamma) and that are identical to
the corresponding human chains, which have aspartic acid at position 73 and
lysine at 104 in contrast to glycine and arginine at these respective
positions of the gorilla A gamma chain. Phylogenetic analysis by the
parsimony method revealed four silent (synonymous) base substitutions in
evolutionary descent of the chimpanzee G gamma and A gamma codons and none
in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla)
coding sequences evolved at one-tenth the average mammalian rate for
nonsynonymous and one-fourth that for synonymous substitutions. Three
sequence regions that were affected by gene conversions between chimpanzee
G gamma and A gamma loci were identified: one extended 3' of the hot spot
with G gamma replaced by the A gamma sequence, another extended 5' of the
hot spot with A gamma replaced by G gamma, and the third conversion
extended from the 5' flanking to the 5' end of intron 2, with G gamma
replaced here by the A gamma sequence. A conversion similar to this third
one has occurred independently in the descent of the gorilla genes. The
four previously identified conversions, labeled C1-C4 (Scott et al. 1984),
were substantiated with the addition of the chimpanzee genes to our
analysis (C1 being shared by all three hominines and C2, C3, and C4 being
found only in humans). Thus, the fetal genes from all three of these
hominine species have been active in gene conversions during the descent of
each species.
相似文献
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cDNA clones encoding bovine gamma-crystallins 总被引:3,自引:0,他引:3
R E Hay W D Woods R L Church J M Petrash 《Biochemical and biophysical research communications》1987,146(1):332-338
We have determined the nucleotide sequence of two bovine lens gamma-crystallin cDNA clones, pBL gamma II-1 and pBL gamma III-1. The 644 bp cDNA insert of pBL gamma II-1 contains coding information for the entire amino acid sequence of bovine gamma II-crystallin. The 497 bp cDNA insert of pBL gamma III-1 encodes a homologous but different gamma-crystallin polypeptide, and appears to lack the coding information for the C-terminal 17 amino acid residues. While the nucleotide and predicted amino acid sequences of the coding regions of the clones show a high degree of homology, the untranslated leader sequences are relatively dissimilar. The leader sequence of pBL gamma III-1 is strikingly homologous to a portion of a rabbit immunoglobulin alpha-heavy chain mRNA. 相似文献
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Genetic variation in immunoglobulin A, the most abundant immunoglobulin in mammalian cells, has not been reported in ruminants.
In this study, variation in the immunoglobulin heavy alpha chain constant gene (IGHA) of sheep was investigated by amplification of a fragment that included the hinge coding sequence, followed by single-strand
conformational polymorphism (SSCP) analysis and DNA sequencing. Three novel sequences, each characterized by unique SSCP banding
patterns, were identified. One or two sequences were detected in individual sheep and all the sequences identified shared
high homology to the published ovine and bovine IGHA sequences, suggesting that these sequences represent allelic variants of the IGHA gene in sheep. Sequence alignment showed that these sequences differed mainly in the 3′ end of exon 1 and in the coding sequence
of the hinge region. There was either a deletion or an insertion of two codons in the hinge coding region in these allelic
variants. Codon usage in the hinge coding region was quite different from that in the non-hinge coding regions of the gene,
suggesting different evolution of the IGHA hinge sequence. Three novel amino acid sequences of ovine IGHA were also predicted, and variation in these sequences might not only affect antigen recognition but also susceptibility to
cleavage by bacterial or parasitic proteases.
Nucleotide sequence data reported in this paper have been submitted to the NCBI GenBank nucleotide sequence database and have
been assigned the accession nos. AY956424–AY956426. 相似文献
13.
H Hayashida T Miyata Y Yamawaki-Kataoka T Honjo J Wels F Blattner 《The EMBO journal》1984,3(9):2047-2053
The nucleotide sequences of the immunoglobulin heavy-chain constant region genes of mouse, C gamma 3, C gamma 1, C gamma 2b and C gamma 2a, together with that of a human equivalent C gamma 4 were compared. All the six pairs of genes within the mouse C gamma gene family contain DNA segments that exhibit marked homology, whereas no such segmental homology was found in interspecies comparisons. This result indicates that the four C gamma genes of the mouse evolved concertedly by exchanging parts of their genetic information with each other either by gene conversion or by double unequal crossing-over. Another example of such concerted evolution was found in gene regions encoding membrane domains of the mouse C gamma chains. We also searched for such segmental homologies in other mammalian C gamma gene families and found at least two more examples in man and guinea-pig. In the mouse C gamma gene family, the silent positions of an exon encoding the third domain of C gamma chains show much greater divergence in sequence than other regions, indicating that the genetic information encoded by this gene region was least scrambled during recent evolution. A phylogenetic tree constructed from the nucleotide differences of this exon demonstrates that at least two C gamma genes had already existed before mammalian radiation. Based on these results, evolution of mammalian C gamma gene families is discussed. 相似文献
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Kappa-chain constant-region gene sequences in genus Rattus: coding regions are diverging more rapidly than noncoding regions 总被引:2,自引:0,他引:2
We have determined the nucleotide sequence of a 1,200-base pair (bp)
genomic fragment that includes the kappa-chain constant-region gene (C
kappa) from two species of native Australian rodents, Rattus leucopus
cooktownensis and Rattus colletti. Comparison of these sequences with each
other and with other rodent C kappa genes shows three surprising features.
First, the coding regions are diverging at a rate severalfold higher than
that of the nearby noncoding regions. Second, replacement changes within
the coding region are accumulating at a rate at least as great as that of
silent changes. Third, most of the amino acid replacements are localized in
one region of the C kappa domain--namely, the carboxy-terminal "bends" in
the alpha-carbon backbone. These three features have previously been
described from comparisons of the two allelic forms of C kappa genes in R.
norvegicus. These data imply the existence of considerable evolutionary
constraints on the noncoding regions (based on as yet undetermined
functions) or powerful positive selection to diversify a portion of the
constant-region domain (whose physiological significance is not known).
These surprising features of C kappa evolution appear to be characteristic
only of closely related C kappa genes, since comparison of rodent with
human sequences shows the expected greater conservation of coding regions,
as well as a predominance of silent nucleotide substitutions within the
coding regions.
相似文献
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Two Drosophila vitelline membrane (VM) genes located at polytene band positions 26A and 34C have been characterized at the nucleotide level. Sequence comparison of the two genes VM26A.1 and VM34C.1 has revealed a similar 114 base pair region centrally located in the coding regions of both genes. The conserved region has a 91% homology at the nucleic acid level and a 100% conservation at the amino acid level. This suggests a common evolutionary origin for these VM genes and indicates that a strong selective pressure exists to maintain a specific polypeptide sequence in a domain of the proteins. 相似文献
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Baboon immunoglobulin constant region heavy chains: identification of four <Emphasis Type="Italic">IGHG</Emphasis> genes 总被引:2,自引:1,他引:1
The increasing use of nonhuman primate models in biomedical research and especially in vaccine development requires the characterization of their immunoglobulin genes and corresponding products. Therefore, we sequenced, cloned and characterized the four immunoglobulin gamma chain constant region genes ( IGHG) present in baboons. These four genes were designated IGHG1, IGHG2, IGHG3 and IGHG4 on the basis of sequence similarities with the four human genes encoding the IgG1, IgG2, IgG3 and IgG4 subclasses and the three known rhesus macaque IGHG genes. Specifically, the baboon IgG1, IgG2, IgG3 and IgG4 sequences exhibit 90.3%, 88.3%, 86.7% and 89.6% amino acid identity to their human counterpart. The percent of amino acid identity of baboon IgG1, IgG2 and IgG3 to the corresponding rhesus macaque sequences is 98.5, 93.1 and 94.4, respectively. Therefore, baboon and rhesus macaque IGHG genes are highly homologous to each other. The majority of differences existing between baboon and human sequences are clustered in the hinge region, with the upper hinge being the most diverse and containing several proline residues. Similar to rhesus macaques, the hinge regions of all baboon IGHG genes consist of a single exon, whereas in humans the IgG3 molecule is encoded by multiple exons. These results confirm the evolutionary instability of the hinge region and indicate that functional properties associated with the hinge regions of baboon and human IgG molecules might differ between the two species. 相似文献
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Isolation and characterization of the rat proenkephalin gene 总被引:14,自引:0,他引:14
The rat proenkephalin gene has been isolated by molecular cloning and characterized by DNA-sequence analysis. The gene exhibits a structural organization similar to that of the human gene. The nucleotide sequence encoding the biologically active opioid peptides which are generated from the proenkephalin precursor as well as the 3' untranslated region of the mRNA are found on a large exon at the 3' end of the gene (Exon III). The nucleotide sequence encoding the N terminus of the mature protein and its signal peptide are located on Exon II while Exon I encodes the 5' untranslated region of the mRNA. The nucleotide sequence of these exons and their flanking regions has been determined and compared to the human proenkephalin gene. Analysis of the nucleotide sequence homology between the human and rat proenkephalin gene reveals the presence of highly conserved regions within both the coding and noncoding portions of the genes. Enkephalin-coding sequences as well as 5' flanking sequences appear to be the most highly conserved. The importance and possible function of these sequences are discussed. 相似文献
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Complete nucleotide and derived amino acid sequences of the fourth component of mouse complement (C4). Evolutionary aspects 总被引:12,自引:0,他引:12
M Nonaka K Nakayama Y D Yeul M Takahashi 《The Journal of biological chemistry》1985,260(20):10936-10943
The nucleotide sequence coding for the fourth component of mouse complement (C4) has been determined from a cloned genomic DNA fragment and a cloned cDNA fragment. The amino acid sequence of the protein was deduced. The single chain precursor protein (pro-C4) consists of 1719 amino acid residues. The mature beta, alpha, and gamma subunits contain 654, 766, and 291 amino acids, respectively. One potential carbohydrate attachment site is predicted for the beta chain, three for the alpha chain, and none for the gamma chain. From a comparison with human C4 cDNA sequence an extensive overall sequence homology, 79% in nucleotides and 76% in amino acids, is observed. There is conservation in both the position and number of cysteine residues in human and mouse C4. We compared the mouse C4 amino acid sequences with those of mouse C3 and human alpha 2-macroglobulin and the evolutionary relationship among these three proteins is discussed. 相似文献