Human dihydrofolate reductase gene organization. Extensive conservation of the G + C-rich 5' non-coding sequence and strong intron size divergence from homologous mammalian genes.
Human dihydrofolate reductase gene organization. Extensive conservation of the G + C-rich 5' non-coding sequence and strong intron size divergence from homologous mammalian genes.
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人类二氢叶酸还原酶基因组织。
DOI：
10.1016/0022-2836(84)90419-4
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发表时间：
1984
影响因子：
5.6
通讯作者：
Attardi,G
中科院分区：
文献类型：
--
作者：
Yang,JK;Masters,JN;Attardi,G
完整的人二氢叶酸还原酶 (DHFR) 基因已从四个重组 lambda 文库中克隆出来，这些重组 lambda 文库是用来自具有扩增的 DHFR 基因的甲氨蝶呤抗性人细胞系的 DNA 构建的。该基因的详细组织结构已通过克隆片段的限制性图谱和所有蛋白质编码区和相邻内含子片段的 DNA 测序确定，并显示与天然人类 DHFR 基因的结构相对应。该基因从 ATG 起始密码子到 3' 非翻译区末端的长度约为 29 × 103 个碱基，并包含五个中断蛋白质编码序列的内含子。内含子的数量和位置与小鼠基因中发现的相同。相比之下，在人、小鼠和中国仓鼠的基因中，同源内含子（第一个除外）的大小差异很大，可达数倍；除连接区域外，内含子序列也表现出很大的分歧。人类和小鼠基因 5' 非编码区之间存在长达数百个核苷酸的惊人序列同源性。这些区域的特点是异常高的 G + C 含量，在人类和小鼠基因中分别为 72% 和 66%，它保留在第一个编码片段和第一个内含子中，与基因其余部分相对较低的 G + C 含量 (~40%) 形成鲜明对比。
The complete human dihydrofolate reductase (DHFR) gene has been cloned from four recombinant lambda libraries constructed with the DNA from a methotrexate-resistant human cell line with amplified DHFR genes. The detailed organization of the gene has been determined by restriction mapping of the cloned fragments and DNA sequencing of all the protein coding regions and adjacent intron segments, and shown to correspond to that of the native human DHFR gene. The gene spans a length of approximately 29 × 103bases from the ATG initiator codon to the end of the 3′ untranslated region, and contains five introns that interrupt the protein coding sequence. The number and positions of introns are identical to those found in the mouse gene. By contrast, the size of the homologous introns (with the exception of the first one) varies greatly, up to several fold, in the genes from man, mouse and Chinese hamster; the intron sequences also exhibit a great divergence, except in the junction regions. A striking sequence homology, extending over several hundred nucleotides, exists between the human and mouse gene 5′ non-coding regions. These regions are characterized by an unusually high G + C content, 72% and 66% in the human and mouse genes, respectively, which is maintained in the first coding segment and first intron, and is in sharp contrast to the relatively low G + C content (~40%) of the remainder of the gene.