Isochores

Abstract Chromosomes of warm‐blooded vertebrates are mosaics of isochores, megabase deoxyribonucleic acid (DNA) stretches that are fairly homogeneous in base composition. In the human genome, isochores can be assigned to five families that cover a very broad range of guanine+cytosine (30–60% GC; this range is narrower in cold‐blooded vertebrates). The isochore structure of the genome led to new insights into a number of important genome features such as (1) the distribution of genes, (2) the structure of chromatin, and (3) the localisation of insertions/deletions and of the integration of proviral sequences. Moreover it also led to (1) the discovery of a set of correlations (collectively called the genomic code) linking coding sequences and extended flanking noncoding sequences, as well as other genome features, (2) the visualisation of the isochore patterns of the genomes as genome phenotypes, that may be conserved or change in evolution, like the classical phenotypes, and (3) the development of the neoselectionist theory of evolution, which explains the two modes, conservative and shifting, of genome evolution. Key Concepts: Isochores are the structural, functional and evolutionary units of the genomes of vertebrates and other eukaryotes. Structurally, isochores correspond to the highest resolution bands of chromosomes. Functionally, isochores from different families are characterised by different frequencies of short oligonucleotides, not only in the extended inter‐ and intragenic noncoding sequences, but also in short regulatory sequences upstream and downstream of coding sequences. Moreover, different categories of genes have a different distribution in isochore families. Evolutionarily, the isochore patterns change in different classes of vertebrates, from the relatively simple (low‐heterogeneity) patterns of cold‐blooded vertebrates to the complex (high‐heterogeneity) of warm‐blooded vertebrates.