Distribution of the mammalian-wide interspersed repeats (MIRs) in the isochores of the human genome

AbstractThe distribution of MIRs (mammalian-wide interspersed repeats) was investigated in 164 human sequences (≥100 kb), which were assigned, according to their GC level, to isochore families L, H1, H2 and H3. MIR elements, whose total number in the genome was estimated to be about 3.3×105, were found to be unevenly distributed in human isochores. The majority of MIRs (55%) were found in the L isochore family. In contrast, MIR density was highest in H2, closely followed by H1, whereas densities in L and H3 were 2- and 3-fold lower than in H2, respectively. For this reason, the assessment of MIR distribution by inter-repeat PCR led to an overestimation of MIR numbers in H2 isochore and an underestimation in L isochores

How Not to Search for Isochores: A Reply to Cohen et al

In a recent paper in these pages, Cohen et al. search for isochores in the human genome, based on a system of attributes that they assign to isochores. The putative isochores that they find and choose for presentation are almost all below 45% GC and cover only about 41% of the genome. Closer inspection reveals that the authors' methodology systematically loses GC-rich isochores because it does not anticipate the considerable fluctuations and corresponding long-range correlations that characterize mammalian DNA and that are highest in GC-rich DNA. Thus, they over-fragment GC-rich isochores (and also many GC-poor isochores) beyond recognition

The Distributions of "New" and "Old" Alu Sequences in the Human Genome: The Solution of a "Mystery"

The distribution in the human genome of the largest family of mobile elements, the Alu sequences, has been investigated for the past 30 years, and the vast majority of Alu sequences were shown to have the highest density in GC-rich isochores. Ten years ago, it was discovered, however, that the small ''youngest'' (most recently transposed) Alu families had a strikingly different distribution compared with the ''old'' families. This raised the question as to how this change took place in evolution. We solved what was considered to be a ''mystery'' by 1) revisiting our previous results on the integration and stability of retroviral sequences, and 2) assessing the densities of acceptor sites TTTT/AA in isochore families. We could conclude 1) that the open state of chromatin structure plays a crucial role in allowing not only the initial integration of retroviral sequences but also that of the youngest Alu sequences, and 2) that the distribution of old Alus can be explained as due to Alu sequences being unstable in the GC-poor isochores but stable in the compositionally matching GC-rich isochores, again in line with what happens in the case of retroviral sequences

The isochore patterns of invertebrate genomes

<p>Abstract</p> <p>Background</p> <p>Previous investigations from our laboratory were largely focused on the genome organization of vertebrates. We showed that these genomes are mosaics of isochores, megabase-size DNA sequences that are fairly homogeneous in base composition yet belong to a small number of families that cover a wide compositional spectrum. A question raised by these results concerned how far back in evolution an isochore organization of the eukaryotic genome arose.</p> <p>Results</p> <p>The present investigation deals with the compositional patterns of the invertebrates for which full genome sequences, or at least scaffolds, are available. We found that (i) a mosaic of isochores is the long-range organization of all the genomes that we investigated; (ii) the isochore families from the invertebrate genomes matched the corresponding families of vertebrates in GC levels; (iii) the relative amounts of isochore families were remarkably different for different genomes, except for those from phylogenetically close species, such as the Drosophilids.</p> <p>Conclusion</p> <p>This work demonstrates not only that an isochore organization is present in all metazoan genomes analyzed that included Nematodes, Arthropods among Protostomia, Echinoderms and Chordates among Deuterostomia, but also that the isochore families of invertebrates share GC levels with the corresponding families of vertebrates.</p

The evolution of isochore patterns in vertebrate genomes

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Mapping Insertions, Deletions and SNPs on Venter's Chromosomes

BACKGROUND:The very recent availability of fully sequenced individual human genomes is a major revolution in biology which is certainly going to provide new insights into genetic diseases and genomic rearrangements. RESULTS:We mapped the insertions, deletions and SNPs (single nucleotide polymorphisms) that are present in Craig Venter's genome, more precisely on chromosomes 17 to 22, and compared them with the human reference genome hg17. Our results show that insertions and deletions are almost absent in L1 and generally scarce in L2 isochore families (GC-poor L1+L2 isochores represent slightly over half of the human genome), whereas they increase in GC-rich isochores, largely paralleling the densities of genes, retroviral integrations and Alu sequences. The distributions of insertions/deletions are in striking contrast with those of SNPs which exhibit almost the same density across all isochore families with, however, a trend for lower concentrations in gene-rich regions. CONCLUSIONS:Our study strongly suggests that the distribution of insertions/deletions is due to the structure of chromatin which is mostly open in gene-rich, GC-rich isochores, and largely closed in gene-poor, GC-poor isochores. The different distributions of insertions/deletions and SNPs are clearly related to the two different responsible mechanisms, namely recombination and point mutations

GC3 of genes can be used as a proxy for isochore base composition: A reply to Elhaik et al.

In an article published in these pages, Elhaik et al. (Elhaik E, Landan G, Graur D. 2009. Can GC content at third-codon positions be used as a proxy for isochore composition? Mol Biol Evol. 26:1829-1833) asked if GC3, the GC level of the third-codon positions in protein-coding genes, can be used as a 'proxy' to estimate the GC level of the surrounding isochore. We use available data to directly answer this simple question in the affirmative and show how the use of indirect methods can lead to apparently conflicting conclusions. The answer reasserts that in human and other vertebrates, genes have a strong tendency to reside in compositionally corresponding isochores, which has far-reaching implications for genome structure and evolution. © 2010 The Author