Human intrachromosomal telomeric-like repeats: sequence organization and mechanisms of origin

The intrachromosomal location of (T(2)AG(3))(n) telomeric sequences has bee n reported in several species. It was proposed that interstitial telomeres (ITs) originated through telomeric fusion of ancestral chromosomes. However , the data so far obtained derive mainly from cytogenetic observations. Clo ning and database searching of human IT sequences allowed us to identify th ree classes: (i) short ITs, composed of few, essentially exact T2AG3 units; (ii) subtelomeric ITs, composed of larger arrays (several hundred base pai rs) including many degenerate units within subtelomeric domains; (iii) fusi on ITs, in which two extended stretches of telomeric repeats are oriented h ead-to-head. The number of short ITs is over 50 and subtelomeric ITs are pr obably present at all chromosomal ends. Surprisingly, the telomeric sequenc e in 2q13 remains the only fusion IT so far characterized, and evidence pre sented here suggests that another member of this class may be present in 1q 41. Different molecular mechanisms generated the three classes. In particul ar, several short ITs interrupt precisely repetitive elements or are flanke d by direct repeats of 10-41 bp, and are conserved in gorilla and chimpanze e. These features strongly suggest that telomeric repeats were inserted at intrachromosomal sites through the repair of double-strand breaks that occu rred in the germline during evolution.