Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three humanchromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions aresubdivided by degenerate (TTAGGG)n repeats into distal and proximal sub-domains with entirely different patterns of homology to other chromosomeends. The distal regions contain numerous, short (<2 kb) segments ofinterrupted homology to many other human telomeric regions. The proximalregions show much longer (approximately 10-40 kb) uninterrupted homology toa few chromosome ends. A comparison of all yeast subtelomeric regionsindicates that they too are subdivided by degenerate TTAGGG repeats intodistal and proximal sub-domains with similarly different patterns ofidentity to other non-homologous chromosome ends. Sequence comparisonsindicate that the distal and proximal sub-domains do not interact with eachother and that they interact quite differently with the correspondingregions on other, non- homologous, chromosomes. These findings suggest thatthe degenerate TTAGGG repeats identify a previously unrecognized,evolutionarily conserved boundary between remarkably different subtelomericdomains.