Gene conversion and polymorphism: Generation of mouse immunoglobulin γ2a chain alleles by differential gene conversion by γ2b chain gene

Ollo, Roger; Rougeon, F

doi:10.1016/0092-8674(83)90471-3

Cited by 120 publications

(43 citation statements)

References 31 publications

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“…In addition, two class I HuIFN-ot genes have been characterized which do not differ in their coding regions while exhibiting completely different restriction maps in their 5' and 3' regions (unpublished data; 58). Similar segmental gene conversion events between nonallelic duplicated genes have been observed for y-globin genes (51), a-globin genes (48), mouse y2a immunoglobulin genes (39), and mouse H-2kb histocompatibility genes (31).…”

Section: Methodsmentioning

confidence: 72%

Two distinct families of human and bovine interferon-alpha genes are coordinately expressed and encode functional polypeptides.

Capon¹,

Shepard²,

Goeddel³

1985

Mol. Cell. Biol.

191

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The classical human interferon-a (HuIFN-a) gene family is estimated to consist of 15 or more nonallelic members which encode proteins sharing greater than 77% amino acid sequence homology. Low-stringency hybridization with a HuIFN-a cDNA probe permitted the isolation of two distinct classes of bovine IFN-a genes. The first subfamily (class I) is more closely related to the known HuIFN-a genes than to the second subfamily (class II) of bovine IFN-a genes. Extensive analysis of the human genome has revealed a HuIFN-a gene subfamily corresponding to the class II bovine IFN-a genes. The class I human and bovine IFN-a genes encode mature IFN polypeptides of 165 to 166 amino acids, whereas the class II IFN-a genes encode 172 amino acid proteins. Expression in Eschenichia coli of members of both gene subfamilies results in polypeptides having potent antiviral activity. In contrast to previous studies which found no evidence of class II IFN-a protein or mRNA expression, we demonstrate that the class I and class II IFN-a genes are coordinately induced in response to viral infection.Interferons are secreted proteins produced by the cells of most vertebrates in response to viruses or other agents and are characterized by their ability to induce an antiviral state in a variety of target cells (reviewed in reference 53). Interferons have been shown to modulate the activity of T and B lymphocytes, natural killer cells, macrophages, and other cells involved in the immune response and to regulate the growth of tumor cells and other proliferating cell types. Several types of interferons have been differentiated on the basis of cellular origin and biochemical and antigenic properties. Interferon-a (IFN-a) and interferon-r (IFN-,3) represent the major interferons synthesized by leukocytes and fibroblasts, respectively, after treatment with viruses, double-stranded RNA, or other inducers. IFN-y is produced by T lymphocytes that have been stimulated by mitogens or specific antigens. Despite many similarities in their biological functions, however, these three types of interferon are distinguished by profound differences in structure and gene organization.Human IFN-a (HuIFN-a) is encoded by a family of at least 15 related genes (15,17,23,26,35,36,55,59,65). The HuIFN-a genes which have been characterized lack introns, and most appear to be functional, although the extent of expression varies greatly (15, 21). The members of this family are related by greater than 85% nucleotide homology in their coding regions. HuIFN-, and HuIFN-y are specified by unique genes (11,16,19,56). The gene for HuIFN-lacks introns (9, 25, 38) and encodes a protein possessing 29% amino acid homology with HuIFN-al, suggesting that IFN-a and IFN-, genes have evolved from a common ancestor (56). By contrast, the HuIFN-y coding region is divided by three introns (18) and exhibits extremely limited amino acid homology with 19). Interestingly, although only a single HuIFN-, gene has been unequivocally identified, bovine IFN-, (BoIFN-P) is encoded by a family of fi...

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Section: Methodsmentioning

confidence: 72%

Two distinct families of human and bovine interferon-alpha genes are coordinately expressed and encode functional polypeptides.

Capon¹,

Shepard²,

Goeddel³

1985

Mol. Cell. Biol.

191

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“…Conceptually, such a correction process between nonallelic genes can be mediated by gene conversion, which is a nonreciprocal exchange of sequences between two genes that rectifies the sequence at the acceptor locus without altering the donor locus (e.g., references 39, 50). Gene conversion has been implicated in sequence exchange among different genes during the evolution of several multigene families such as the -y-globins (55), mouse histocompatibility genes (42,61), immunoglobulins (3,41), and chicken embryonic 8-and E-globin genes (49). Alternatively, multiple nonequal recombination events between nonallelic loci can also generate a pattern of segmental sequence identity such as is observed between the (31 and (2 tubulin genes.…”

Section: Discussionmentioning

confidence: 99%

Apparent gene conversion between beta-tubulin genes yields multiple regulatory pathways for a single beta-tubulin polypeptide isotype.

Sullivan¹,

Lau²,

Cleveland³

1985

Mol. Cell. Biol.

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We have determined the complete nucleotide sequences of two chicken 0-tubulin genes, 11 and I2. These genes display an unusual pattern of segmental homology which indicates that they originally arose by gene duplication and have subsequently coevolved by a process that included localized gene conversion or intergenic recombination. Since the ,I-tubulin polypeptides encoded by the two genes are virtually identical (99.5%), particularly in the major j-tubulin isotype defining regions, they almost certainly constitute a single isotypic class of j8 tubulin. However, the regulatory properties of the two genes are highly divergent as indicated by analysis of their patterns of expression in different chicken cell types. I1 is the major transcript detected in skeletal muscle myoblasts, whereas ,2 is the major f3-tubulin transcript in cultured sympathetic neurons. The existence of these two genes appears to derive from a regulatory requirement whereby the expression of a single tubulin isotype is mediated through different regulatory programs in development and differentiation. These results thus provide direct experimental support for the hypothesis that gene conversion and intergenic recombination play an important role in evolution by uncoupling the evolution of structural genes from the regulatory sequences which control them.The principal structural subunit of eucaryotic microtubules is the protein tubulin, a heterodimer which is comprised of related but nonidentical a and ,B polypeptides (29). Such microtubules are prominent filamentous structures which are found in eucaryotic cells and comprise an integral element of the cytoskeleton as well as of the mitotic apparatus, elongated neuronal processes, and eucaryotic cilia and flagella. The cellular functions even within the class of ubiquitous cytoskeletal microtubules are diverse. For example, these microtubules are important in executing changes in cell shape during embryogenesis (e.g., references 6, 26), in mediating the transport of substances and organelles within the cytoplasm (e.g., references 22, 38), and possibly in transduction of signals originating at the cell membrane (34). Thus, two important questions regarding the function of microtubules are immediately evident. First, how does a single structural element function in such diverse roles, and second, how is the expression of tubulin and other microtubule-associated proteins integrated with different programs that determine cell structure and function?Recently, with the isolation of tubulin DNA sequences by molecular cloning techniques (for review see references 10 and 13), the outlines of an answer to these questions have begun to emerge. Analysis of a number of higher eucaryotic genomes has demonstrated that genes for both the ax-and the P-tubulin polypeptides are present as dispersed, multigene families in most, if not all, metazoan species (1,12,16,25,31,32,51). To the important and unresolved question of the functional significance of tubulin multigene families (a general question which in fact re...

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“…There are abundant data to indicate that the ␥2a a gene and the ␥2a b gene are not alleles, but two different genes (15)(16)(17)(18)(19). Hence, Jouvin-Marche and colleagues (15,19) have suggested that the ␥2a b gene be renamed ␥2c.…”

Section: Induced Expression Of Murinementioning

confidence: 99%

Induced Expression of Murine γ2a by CD40 Ligation Independently of IFN-γ

Collins

Shi

Burrell

et al. 2006

The Journal of Immunology

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IgG2a, with γ2a H chains, is important for protection against viruses and other intracellular pathogens. Although a large portion of IgG2a expression is dependent upon IFN-γ, some germline transcription and switch recombination to the murine γ2a H chain gene expression are independent of IFN-γ. We found that agonistic anti-CD40 Abs injected into IFN-γ-deficient mice induce a >200-fold increase in the amount of serum Ig2a, while other Ig isotypes are increased by 16-fold or less. In vitro, ligation of CD40 on B cells, without the addition of other B cell activators or cytokines, results in germline transcription and switch recombination that are largely restricted to the γ2a gene. These results suggest that some immune responses to infectious agents can result in large amounts of IgG2a expression through ligation of CD40, without the expression of IFN-γ by Th1 or other cells.

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Gene conversion and polymorphism: Generation of mouse immunoglobulin γ2a chain alleles by differential gene conversion by γ2b chain gene

Cited by 120 publications

References 31 publications

Two distinct families of human and bovine interferon-alpha genes are coordinately expressed and encode functional polypeptides.

Two distinct families of human and bovine interferon-alpha genes are coordinately expressed and encode functional polypeptides.

Apparent gene conversion between beta-tubulin genes yields multiple regulatory pathways for a single beta-tubulin polypeptide isotype.

Induced Expression of Murine γ2a by CD40 Ligation Independently of IFN-γ

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