Isochore chromosome maps of eukaryotic genomes

Analytical DNA ultracentrifugation revealed that eukaryotic genomes are mos aics of isochores: long DNA segments ( >> 300 kb on average) relatively hom ogeneous in G + C. Important genome features are dependent on this isochore structure, e.g. genes are found predominantly in the GC-richest isochore c lasses. However, no reliable method is available to rigorously partition th e genome sequence into relatively homogeneous regions of different composit ion, thereby revealing the isochore structure of chromosomes at the sequenc e level. Homogeneous regions are currently ascertained by plain statistics on moving windows of arbitrary length, or simply by eye on G + C plots. On the contrary, the entropic segmentation method is able to divide a DNA sequ ence into relatively homogeneous, statistically significant domains. An ear ly version of this algorithm only produced domains having an average length far below the typical isochore size. Here we show that an improved segment ation method, specifically intended to determine the most statistically sig nificant partition of the sequence at each scale, is able to identify the b oundaries between long homogeneous genome regions displaying the typical fe atures of isochores. The algorithm precisely locates classes II and III of the human major histocompatibility complex region, two well-characterized i sochores at the sequence level, the boundary between them being the first i sochore boundary experimentally characterized at the sequence level. The an alysis is then extended to a collection of human large contigs. The relativ ely homogeneous regions we find show many of the features (G + C range, rel ative proportion of isochore classes, size distribution, and relationship w ith gene density) of the isochores identified through DNA centrifugation. I sochore chromosome maps, with many potential applications in genomics, are then drawn for all the completely sequenced eukaryotic genomes available. ( C) 2001 Elsevier Science B.V. All rights reserved.