EVOLUTION OF MEGASATELLITE DNA.

RS447巨卫星DNA在人类4PL5上重复20-100次，具有高变异性和高度多态特性。在4746bp的单位大小中，存在一个1590bp的开放阅读框，编码脱泛素酶USP17，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实验分析模型系统，本研究对中国仓鼠和大鼠RS447同源物的分离基因组克隆进行了分析。携带人类RS447的转基因小鼠创始人也被操纵以建立纯合子系。与数据库中的小鼠DUB-1和DUB-2的DNA序列比较表明，人RS447与任何啮齿动物同源物的相似性约为60%。中国仓鼠为75条，大鼠为10条，小鼠为1条。在物种内发现了99.3%以上的同源性，而小鼠DUB和大鼠RS447之间的同源性只有77%是物种之间最高的。基于这些结果，可能的…在之前的研究中已经提出了更多的保守进化。在人类中，RS447主要位于4p5，少数位于8p5。FISH和作图分析表明，大鼠RS447同源基因仅位于第一染色体上。据报道，小鼠DUB-1和-2位于第7染色体上。小鼠7与大鼠I的共性关系已有报道，但在人4PL5中未见报道。因此，这可能是人与啮齿动物共性的新发现。携带人RS447的转基因小鼠已经进行了交配，以获得纯合子。转基因后代出生时总是比预期的要小。到目前为止，纯合子还没有获得。这可能意味着RS447的串联重复对小鼠是有害的。有趣的是，这些反义转录本在人类身上被检测到。尤其是在大脑中表现突出。然而，在大鼠中，该基因在脾中的表达明显丰富，到目前为止还没有检测到反义基因的表达。似乎有必要研究分离的啮齿动物RS447同源基因是同源基因还是同源基因。RS447巨卫星DNA与小鼠p^&lt；un&gt；逆转系统一起显示了体细胞的基因组高度变异性，为研究基因组动态和进化提供了工具。较少

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