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STRUCTURAL ANALYSIS OF RS447 MEGASATELLITE DNA.

RS447 大卫星 DNA 的结构分析。

基本信息

批准号：
10640602
负责人：
GONDO Yoichi
金额：
$ 2.43万
依托单位：
RIKEN (1999)Tokai University (1998)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

We proposed the concept of "megasatellite DNA" and it has been widely accepted. The RS447 megasatellite DNA was firstly identified on human 4p15. The unit size of 4746bp is tandemly repeated about 20 to 100 times. The copy number is highly polymorphic and indeed hypervariable. By pedigree analysis, 6 out of 60 parent-to-offspring transmission exhibited copy-number changes. This novel repetitive sequence is, however, neither junk nor selfish DNA. There is an ORF of 1590 bp that codes for an active deubiquitinase. The RS447 sequence is conserved in mammals. The RS447 homologs have been cloned from the Chinese hamster and rat. The tandemly repeated structure is well conserved in all the tested mammalian specied except the mouse. Thus, in order to elucidate the structural function and its evolution, the comparative studies of the RS447 homologs among human and those rodents has been conducted. Sequencing of independent copies RS447 of the human, Chinese hamster and rat indicated more than 99% identities within the species but much lower between the species although there are significantly high homologies. It implies the RS447 tandem repeat is homogenized within species by some mechanism(s) like concerted evolution. At this moment, it is an enigma why RS447 homologs is dispersed distributed in the mouse genome. We have constructed 12 independent transgenic mouse strains which tandemly carry the human RS447 as transgene. These transgenic mice should provide a clue to understand the RS447 structure and evolution in the mouse.

我们提出了“巨卫星DNA”的概念，并得到了广泛的接受。 RS447 巨卫星 DNA 首次在人类 4p15 上发现。 4746bp的单元大小串联重复约20至100次。拷贝数具有高度多态性并且确实高度可变。通过谱系分析，60 个亲代到后代的传播中，有 6 个表现出拷贝数变化。然而，这种新颖的重复序列既不是垃圾，也不是自私的 DNA。有一个 1590 bp 的 ORF，编码活性去泛素酶。 RS447 序列在哺乳动物中是保守的。 RS447同源物已从中国仓鼠和大鼠中克隆出来。除小鼠外，串联重复结构在所有测试的哺乳动物物种中都非常保守。因此，为了阐明其结构功能及其进化，对人类和啮齿类动物的RS447同源物进行了比较研究。对人类、中国仓鼠和大鼠的独立副本 RS447 进行测序表明，物种内的同一性超过 99%，但物种之间的同一性要低得多，尽管同源性显着较高。这意味着 RS447 串联重复序列通过协同进化等机制在物种内实现同质化。目前，RS447同源物为何分散分布在小鼠基因组中仍是一个谜。我们构建了12个独立的转基因小鼠品系，它们串联地携带人类RS447作为转基因。这些转基因小鼠应该为了解小鼠的 RS447 结构和进化提供线索。