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小鼠免疫球蛋白轻链基因在体细胞变化前后的序列。

Sequences of mouse immunoglobulin light chain genes before and after somatic changes.

作者信息

Bernard O, Hozumi N, Tonegawa S

出版信息

Cell. 1978 Dec;15(4):1133-44. doi: 10.1016/0092-8674(78)90041-7.

Abstract

We have determined the nucleotide sequences of the germ line gene as well as a corresponding somatically mutated and rearranged gene coding for a mouse immunoglobulin lambdaI type light chain. These sequencing studies were carried out on three Eco RI-DNA fragments which had been cloned from BALB/c mouse embryos or a lambdaI chainsecreting myeloma, H2020. The embryonic DNA clone Ig 99lambda contains two protein-encoding segments, one for the majority of the hydrophobic leader (L) and the other for the rest of the leader and the variable (V) region of the lambda0 chain (Cohn et al., 1974); these segments are separated by a 93 base pair (bp) intervening sequence (I-small). The coding of the V region ends with His at residue 97. The second embryonic DNA clone Ig 25lambda includes a 39 bp DNA segment (J) coding for the rest of the conventionally defined V region (that is, up to residue 110), and also contains the sequence coding for the constant (C) region approximately 1250 untranslated bp (I-large) away from the J sequence. The J sequence is directly linked with the V-coding sequence in the myeloma DNA clone, Ig 303lambda, which has the various DNA segments arranged in the following order: 5' untranslated region, L, l-small, V linked with J, l-large, C, 3' untranslated sequence. The lg 303lambda V DNA sequence codes for the V region synthesized by the H2020 myeloma and is different from the lg 99lambda V DNA sequence by only two bases. No silent base change was observed between the two DNA clones for the entire sequence spanning the 5' untranslated regions and the V-coding segments. These results confirm the previously drawn conclusion that an active complete lambdaI gene arises by somatic recombination that takes place at the ends of the V-coding DNA segment and the J sequence. No sequence homology was observed at or near the sites of the recombination.

摘要

我们已经确定了种系基因以及编码小鼠免疫球蛋白λI型轻链的相应体细胞突变和重排基因的核苷酸序列。这些测序研究是在从BALB/c小鼠胚胎或分泌λI链的骨髓瘤H2020中克隆的三个Eco RI-DNA片段上进行的。胚胎DNA克隆Ig 99λ包含两个蛋白质编码片段,一个用于大部分疏水前导肽(L),另一个用于前导肽的其余部分和λ0链的可变(V)区(科恩等人,1974年);这些片段被一个93个碱基对(bp)的间隔序列(I-小)隔开。V区的编码在第97位残基处终止于组氨酸。第二个胚胎DNA克隆Ig 25λ包括一个39 bp的DNA片段(J),编码传统定义的V区的其余部分(即直至第110位残基),并且还包含编码恒定(C)区的序列,该序列距离J序列约1250个非翻译bp(I-大)。J序列在骨髓瘤DNA克隆Ig 303λ中与V编码序列直接相连,其各种DNA片段按以下顺序排列:5'非翻译区、L、I-小、与J相连的V、I-大、C、3'非翻译序列。Ig 303λ V DNA序列编码由H2020骨髓瘤合成的V区,与Ig 99λ V DNA序列仅相差两个碱基。在跨越5'非翻译区和V编码片段的整个序列中,两个DNA克隆之间未观察到沉默碱基变化。这些结果证实了先前得出的结论,即一个活跃的完整λI基因是通过在V编码DNA片段末端和J序列处发生的体细胞重组产生的。在重组位点或其附近未观察到序列同源性。

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