isochores

An isochore is a long, quasi-continuous region of DNA within a genome whose base composition—particularly GC content—varies little across its length. The concept was proposed in 1979 by Bernardi to describe a mosaic genome composed of regions with distinct GC content. In vertebrates, the genome is commonly parsed into five major isochore families ranging from GC-poor to GC-rich, often labeled L1, L2, H1, H2, and H3 (or, in alternate schemes, L, M, and H). Isochore L1 is markedly GC-poor; H3 is among the GC-richest regions; the intermediate families fill the spectrum. These categories are approximate and boundaries are not sharp; genomes host a continuum of GC values, with stretches of varying composition.

Isochores correlate with several genomic properties. GC-rich isochores tend to be gene-rich, contain more CpG islands, and exhibit higher density of expressed sequences; they also show early DNA replication timing and open chromatin features. GC-poor isochores usually have lower gene density, fewer CpG islands, late replication timing, and are more often associated with closed chromatin and lamina-associated domains. Recombination rates and mutation spectra also vary with GC content.

The isochore concept has profoundly influenced views of genome organization, but its universality and the clarity of boundaries are debated. Modern analyses recognize that genomes are mosaic with gradual transitions and that the isochore framework captures a broad, useful pattern rather than a strict architectural law. Isochores are most clearly observed in vertebrate genomes and are less pronounced in some lineages.