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The mouse genome is a mosaic of isochores, consisting of long (>300 kb), compositionally homogeneous DNA segments that can be divided into two GC-poor families, L1 and L2, representing 56% of the genome, and two GC-rich families, H1 and H2, representing 26% and 7% of the genome, respectively, the remaining 11% being formed by satellite and ribosomal DNAs. (GC is the molar fraction of guanine + cytosine in DNA.) The mouse genome differs from the human genome (which is representative of most mammalian genomes) because it shows a narrower compositional spectrum of isochores and it has a karyotype formed exclusively by acrocentric chromosomes. The chromosomal distribution of the four isochore families, as investigated here by in situ hybridization of single-copy sequences from compositional DNA fractions, has shown that G(iemsa) bands are essentially composed of GC-poor isochores, whereas R(everse) bands comprise three subsets of bands: R′ bands, containing GC-poor isochores and GC-rich isochores of the H1 family, and T and T′ bands, containing all H2 isochores (in addition to other isochores), the former containing a higher proportion of H2 isochores than the latter. Mouse T and T′ bands are generally syntenic with, and are compositionally related to, human T and T′ bands and have the highest gene concentrations. These findings indicate that the distribution of isochore families and genes in chromosomal bands is basically similar in mouse and in human genomes, in spite of their remarkable differences and their extremely large phylogenetic distance.