The evolution of isochore patterns in vertebrate genomes

Abstract

Background: Previous work from our laboratory showed that (i) vertebrate genomes are mosaics of isochores, typically megabase-size DNA segments that are fairly homogeneous in base composition; (ii) isochores belong to a small number of families (five in the human genome) characterized by different GC levels; (iii) isochore family patterns are different in fishes/amphibians and mammals/birds, the latter showing GC-rich isochore families that are absent or very scarce in the former; (iv) there are two modes of genome evolution, a conservative one in which isochore patterns basically do not change (e.g., among mammalian orders), and a transitional one, in which they do change (e.g., between amphibians and mammals); and (v) isochores are tightly linked to a number of basic biological properties, such as gene density, gene expression, replication timing and recombination.

Results: The present availability of a number of fully sequenced genomes ranging from fishes to mammals allowed us to carry out investigations that (i) more precisely quantified our previous conclusions; (ii) showed that the different isochore families of vertebrate genomes are largely conserved in GC levels and dinucleotide frequencies, as well as in isochore size; and (iii) isochore family patterns can be either conserved or change within both warm- and cold-blooded vertebrates.

Conclusion: On the basis of the results presented, we propose that (i) the large conservation of GC levels and dinucleotide frequencies may reflect the conservation of chromatin structures; (ii) the conservation of isochore size may be linked to the role played by isochores in chromosome structure and replication; (iii) the formation, the maintainance and the changes of isochore patterns are due to natural selection.

Figure 1

Distribution of isochores according to GC levels. The histograms show the distribution (by weight; see Text) of isochores as pooled in bins of 0.5% GC from chimpanzee, dog, mouse, opossum and platypus. Total amounts of sequences are calculated from the sums of isochores; colors represent the five isochore families. Values at minima were split between the two neighbouring families (histogram bars with mixed colors). A comparable plot for the human genome [3] is reported for the sake of comparison.

Figure 2

Distribution of isochores according to GC levels. The histograms show the distribution (by weight; see Text) of isochores as pooled in bins of 0.5% GC from fish [6] and chicken isochores [7]. See also legend of Figure 1.

Figure 3

The amounts of DNA in human and medaka chromosomes, as well as in scaffolds of anolis and xenopus were partitioned into non-overlapping 100 kb windows and pooled in 1% GC bins.

Figure 4

Comparison of dinucleotide frequencies in eutherian genomes. Observed/expected frequencies for dinucleotides in 100-kb DNA segments in the isochore families from human, mouse, opossum and platypus. The lines between points are only used to make an easier comparison of the values from each genome.

Figure 5

Comparison of dinucleotide frequencies of human, reptiles and amphibians. See also legend of Figure 4.

Figure 6

Comparison of dinucleotide frequencies of human and fishes. See also legend of Figure 4.

Figure 7

Average size of isochores belonging in the five isochore families for all the vertebrates tested. The data for human, fishes [6] and chicken [7] are reported for the sake of comparison. A horizontal guideline at 0.9 Mb correspond to the average size of isochores in the human genome [3]. A vertical line is drawn to divide mammals and chicken from the fishes. Asterisks refer to sizes that are probably overestimated (see Text and Table 1).

Figure 8

Gene density. The histograms represent the gene density, as density of available genes per megabase, in the five isochore families (L1, L2, H1, H2 and H3) for chimpanzee, dog, mouse, opossum and platypus; the data published on human, chicken [7] and fishes [6] are reported for the sake of comparison. The gene density for xenopus is calculated on scaffolds partitioned into non-overlapping 100 kb windows, according to the borders of human isochore families.