Structure et évolution des régions sous-télomériques de l’Homme

Structure and evolution of human subtelomeric domains

¹ Laboratoire IECH, Institut de Génétique et Microbiologie, Université Paris-Sud, 91405 Orsay Cedex.
² Unité de Génétique Moléculaire, Centre d’Études du Bouchet, 91710 Vert le Petit.

Résumé

Des travaux récents d’analyse structurale du génome humain conduisent à considérer les régions sous-télomériques comme des domaines fonctionnels et comme des sites privilégiés d’évolution rapide du génome. Ce texte présente les principales investigations ayant conduit au développement de ces nouveaux concepts de régions sous télomériques distales, régions sous-télomériques proximales, régions sous-télomériques chromosome-spécifique. Les travaux réalisés rendent possibles de nouvelles études sur l’évolution récente des populations humaines.

Abstract

Recent progress in the field of human genome analysis has led to the development of new concepts in the definition of subtelomeric domains. Analysis of DNA sequences from human and yeast chromosome ends have shown that short stretches of degenerate TTAGGG are found at a distance from the telomeric repeats. These stretches define a boundary between two structurally different regions. The distal domain is characterised by numerous, short segments of interrupted homology to many other human telomeric regions and to a number of ESTs. The proximal domain shows much longer uninterrupted homology to a few chromosome ends. This domain evolved quickly within primates at least, as demonstrated by the detailed study of locus DNF92 which spread very recently in humans from 17qter to at least ten other chromosome ends. At the different sites, presence-absence polymorphisms are observed within humans. The region remained single locus at the paralogous site in higher primates. Conversely, a human and orangutan single locus telomeric domain occupies multiple chromosome ends in chimpanzee. Balanced translocation is the likely mechanism through which the spreading occurred. Some members of the olfactory receptor gene family show a similar behaviour: multiple telomeric locations, and presence-absence polymorphism. Strikingly, the set of chromosome ends occupied by the two regions is identical, except for the two ancestral sites. Moreover, the relative frequency of detection of the region at the different sites indicates some kind of competition between the two regions. Consequently, these two regions represent major new tools to investigate recent human genome evolution and human genome diversity in different populations.