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

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