International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

D18 Megasatellite DNA: Human RS447 and Its Homologs in Rodents

Yoichi Gondo1,2, Yoshinori Okada3, Takeya Okada2, Yasushi Saitoh4, Yoshiko Yanagisawa5, Joh-E Ikeda2,5. 1RIKEN, Genomic Sciences Center; 2The Institute of Medical Sciences and 3School of Medicine, Tokai University; 4Dept. of Agricul., Tohoku University; 5The NeuroGenes Project, ICORP, JST

A novel large tandemly repeated sequence was identified on human 4p15 (Kogi et al., Genomics 42, 278, 1997). The unit sequence RS447 is 4746 bp that contains 1590 bp of a large ORF encoding for an active deubiquitinating enzyme. The copy number of the tandem repeats was highly polymorphic in a human population and well conserved in all the tested mammalian species, monkey, dog, cow, rabbit, pig, rat, mouse and Chinese hamster. We have designated this new class of head-to-tail tandem repeat "megasatellite DNA" (Gondo et al., Genomics 54, 39-49, 1998). Pedigree analyses indicated that the copy number was indeed highly variable. Six cases out of 60 parent-to-offspring transmissions exhibited the copy number changes. This variability rate per generation, 10%, corresponds to the highest instability so far identified in mammalian genomes like minisatellite DNA. In order to understand the mechanism of the hypervariability, function of the coded deubiquitinating enzyme and evolution of RS447 megasatellite DNA, we have been isolating and characterizing RS447 homologs in other species. So far, RS447 homologs have been isolated from Chinese hamster and rat, both of which also exhibited the head-to-tail tandem repetitive structure in each genome and coded a putative deubiquitinase. The mouse genome, on the other hand, did not carry any tandemly repeated RS447 homologs but contained many dispersed counterparts. The DNA database search identified that sequences of human, Chinese hamster and rat RS447 have the highest homology to those of mouse deubiquitinating enzymes DUB-1 and DUB-2. The megasatellite DNAs, thus, seem to have already existed before the mammalian speciations. In mouse, however, the tandem structure has been somehow lost after mouse was separated from the common ancestor of the rodent family. In addition, the sequence comparison of RS447 copies within and among these species implies the concerted evolution between tandemly repeated copies within species.

 


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