STRUCTURAL ANALYSIS OF RS447 MEGASATELLITE DNA.

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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.