An isochore map of human chromosomes

Abstract

Isochores are large DNA segments (≫300 kb on average) that are characterized by an internal variation in GC well below the full variation seen in the mammalian genome. Precisely defining in terms of size and composition as well as mapping the isochores on human chromosomes have, however, remained largely unsolved problems. Here we used a very simple approach to segment the human chromosomes de novo, based on assessments of GC and its variation within and between adjacent regions. We obtain a complete coverage of the human genome (neglecting the remaining gaps) by ∼3200 isochores, which may be visualized as the ultimate chromosomal bands. Isochores visibly belong to five families characterized by different GC levels, as expected from previous investigations. Since we previously showed that isochores are tightly linked to basic biological properties such as gene density, replication timing, and recombination, the new level of detail provided by the isochore map will help the understanding of genome structure, function, and evolution.

Sister chromatid telomere fusions, but not NHEJ-mediated inter-chromosomal telomere fusions, occur independently of DNA ligases 3 and 4

“…4D). Mean GC content (Costantini et al 2006;Pratto et al 2014) of junction-proximal sequence extracted for these and LIG4 −/− samples (Supplemental Fig. 4E) was also correspondingly lower than WT cells (P = 0.0477 and P = 0.0445 in respective pairwise analyses), supporting the potential for distinct mechanisms and for sequence context to be permissive for long-range LIG4-independent repair.…”

Replication timing, chromosomal bands, and isochores

“…Complete coverage of the human genome comprises Ϸ3,200 isochores having an average size of 0.9 Mb (14,15). This prompted a new comparison with the replication maps of chromosomes 21q and 11q (11) and of chromosome 6 (16), which is presented here.…”

Segmentation with an Isochore Distribution

“…An isochore is a long contiguous segment of genomic DNA with a "fairly homogeneous" guanine+cytosine (GC) content [9]. The old debate about the theory's utility reemerged at the completion of the human genome draft sequence and persists to this day [9][10][11][12][13]. Eyre-Walker and Hurst [14] review biologically relevant issues in conjunction with isochores.…”

“…We do not want to settle the question of biological relevance, but rather treat isochores as a technically useful concept describing the "fairly homogeneous" GC content of a region within an environment of at least 50-300 thousand base pairs. Usual isochore computations involve sliding windows of fixed length [10,11,13,14]. Window-less methods usually correspond to the minimization of some segment homogeneity measure [2,15].…”