EVOLUTION OF MEGASATELLITE DNA.

RS 447巨卫星DNA在人4p 15上串联重复20 - 100次，具有高度变异性和多态性。在4746 bp的基因单元中，有一个1590 bp的编码去泛素化酶USP 17的开放阅读框，至少在哺乳动物基因组中是保守的。为了研究基因组进化，以及建立有用的模型系统的实验分析，分离的基因组克隆RS 447同源物从中国仓鼠和大鼠进行了分析。携带人RS 447的转基因小鼠创始人也被操纵以建立纯合系。DNA序列与来自数据库的小鼠DUB-1和DUB-2的比较显示人RS 447与任何啮齿类同源物之间约60%的相似性。中国仓鼠、大鼠和小鼠的拷贝数分别为75、10和1个。物种内的同源性超过99.3%，但小鼠DUB和大鼠RS 447之间的同源性仅为77%，是物种间最高的。根据这些结果， ...更多信息 在以前的研究中已经提出了保守进化的可能性。在人类中，RS 447主要位于4p 15上，少数位于8 pter上。通过FISH和图谱分析，大鼠RS 447同源物仅位于染色体I上。据报道，小鼠DUB-1和DUB-2位于7号染色体上。小鼠7与大鼠I的同线性关系已有报道，但与人4p 15的同线性关系未见报道，因此，这可能是人与啮齿类动物间同线性关系的新发现。携带人RS 447的转基因小鼠系已交配以获得纯合子。转基因同窝出生的婴儿总是比预期的要少。目前尚未获得纯合子。这可能意味着RS 447的串联重复序列对小鼠有害。有趣的是，在人类中检测到反义转录物。在脑组织中尤为突出。然而，在大鼠中，脾脏中的表达明显丰富，迄今尚未检测到反义表达。因此，有必要对分离到的啮齿类RS 447同源基因进行同源性研究。RS <un>447巨卫星DNA与小鼠体细胞基因组高度变异的逆转录系统一起，为研究体细胞基因组动态和进化提供了一个工具。少

RS447 megasatellite DNA repeated 20 - 100 times tandemly on human 4pl5.It is hypervariable and highly polymorphic. In the unit size of 4746 bp, there is an ORF of 1590 bp encoding for deubiquitinase USP17, that is well conserved in at least mammalian genomes. To study genome evolution as well as to establish useful model systems for experimental analyses, isolated genomic clones for RS447 homologs from Chinese hamster and rat have been analysed in this study. Transgenic mouse founders carrying human RS447 have also been manipulated to establish homozygous lines. DNA sequence comparison together with mouse DUB-1 and -2 from database exhibited about 60% similarities between human RS447 and any of the rodent homologs. The copy numbers were 75, 10 and single for Chinese hamster, rat and mouse, respectively. More than 99.3% homologies within the species were found, yet only 77% homology between mouse DUB and rat RS447 was the highest between the species. Based upon these results, the possib … More ility of conserted evolution had already been proposed in the previous study. In human, RS447 resided mainly on 4pl5 and a few on 8pter. The FISH and mapping analyses, rat RS447 homolog was located only on chromosome I. It has been reported that mouse DUB-1 and -2 are on chromosome 7 by the other investigators. The synteny relation between mouse 7 and rat I has been reported but not to human 4pl5.Therefore, it may be a new finding of synteny between human and rodents. The transgenic mouse lines carrying human RS447 have been mated to obtain homozygotes. The transgenic littermates were born always less than expected. The homozygotes have not obtained so far yet. It may imply that the tandem repeat of RS447 would be detrimental to the mouse. Intriguingly, the antisense transcripts were detected in human. It was prominent in brain particularly. In the rat, however, the expression was clearly abundant in spleen and no antisense expression has been so far detected. It seems to be necessary to study if the isolated rodent RS447 homologs are authologs or paralogs. Together with the mouse p^<un> reversion system that exhibits the genomic hypervariability in somatic cells, RS447 megasatellite DNA provide a tool to investigate the genome dynamics and evolotion. Less