EVOLUTION OF MEGASATELLITE DNA.

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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