The Major Components of the Mouse and Human Genomes

Cuny, G; Soriano, Philippe; Macaya, Gabriel; Bernardi, Giorgio

doi:10.1111/j.1432-1033.1981.tb05227.x

Cited by 148 publications

(110 citation statements)

References 48 publications

(33 reference statements)

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“…The estimates of d G + dC contents of the major components as calculated from QO values were systematically higher than those obtained by direct nucleoside analysis. This discrepancy was also found for the major components of mouse and human DNAs [8] and is apparently due to a different frequency of short oligonucleotide sequences in these vertebrate DNAs compared to the bacterial DNAs used in establishing the d G + dC vs ,oo relationship. Finally, the compositional heterogeneities (Fig.…”

Section: Other Materials and Met1~1drmentioning

confidence: 82%

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Organization of Nucleotide Sequences in the Chicken Genome

Olofsson¹,

Bernardi²

1983

European Journal of Biochemistry

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The four major components of chicken D N A were prepared by density gradient centrifugation and characterized in several basic properties: relative amounts, d G + d C content, buoyant densities, compositional heterogeneity, and reassociation kinetics. While the relative amounts and the compositions of the major components of chicken DNA were similar to those found in mammalian genomes, their compositional hetei-ogeneities were found to be narrower. The relative amounts of interspersed repeated and unique sequences were strikingly different in different components and also different from those found in the corresponding major components of mouse and human DNAs. If one takes into consideration that major D N A components (a) account for practically all of main-band D N A and (b) derive by preparative breakage from very long DNA segments of fairly homogeneous composition, the isochores, our findings indicate that the distribution of interspersed repeats is different in different chromosomal regions and is species-specific.Equilibrium density gradient centrifugation in the presence of DNA ligands has been applied in our laboratory to investigate the nucleotide sequence organization of the genomes of eukaryotes and, more particularly, of vertebrates [I -81. This approach has led us, so far, to several conclusions. The first one is that, neglecting satellite and minor components, the genomes of higher, warm-blooded vertebrates can be resolved into four families of fragments, the major DNA components. Two of these components (not resolved in some species) represent about two thirds of the main-band D N A and have densities in the range 1.697-1.702 g/cm3, whereas the other two represent about 25 "/, and 10 "/, and have densities of 1.704 and 1.708 g/cm3, respectively.Both the relative amounts and the buoyant densities of the major components show little variation in different mammalian and avian genomes. In contrast, DNAs from lower, cold-blooded vertebrates have buoyant densities which are, in most cases, in the same range as the light components of warm-blooded vertebrates; these DNAs d o not show the compositional heterogeneity of DNAs from higher vertebrates and cannot be resolved into families of fragments equivalent to the major components mentioned above.The second conclusion is that the four major components of warm-blooded vertebrates are families of DNA fragments derived, by preparative breakage, from very long DNA segments (3 x lo5 residues in the mouse genome) fairly homogeneous in base composition, the isochores, possibly corresponding to chromosomal bands. Furthermore, unique, interspersed repeated and foldback sequences show a different distribution in the major components of mouse and human DNAs, and also in corresponding major components of these mammalian DNAs. The first finding points to a sequence interspersion pattern which varies in different chromosomal regions; the second one to an unsuspected variety of sequence arrangements in mammals.In the present work we have investigated the basic propertie...

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Section: Other Materials and Met1~1drmentioning

confidence: 82%

“…Finally, the compositional heterogeneities (Fig. 3) of the isolated major components were remarkably small not only when compared with that of total chicken DNA, but also with the values for the major components of mouse and human DNAs [8].…”

Section: Other Materials and Met1~1drmentioning

confidence: 96%

Organization of Nucleotide Sequences in the Chicken Genome

Olofsson¹,

Bernardi²

1983

European Journal of Biochemistry

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“…Via the relation GC3 = 2.92 GC ‫מ‬ 74.3% , the GC3 values would correspond to estimated bulk DNA components (Macaya et al 1976;Cuny et al 1981;Bernardi et al 1985) at 38.7%, 48.3%, 58.1%, 72.7%, and 84% GC3.…”

Section: Peak Locations Comparison With Experimental Results Using Gmentioning

confidence: 99%

“…The discovery of isochores was accompanied by the identification, and physical isolation, of a small number of DNA components of increasing GC level in several vertebrate species (Macaya et al 1976;Cuny et al 1981;Olofsson and Bernardi 1983;Bernardi et al 1985). The isochores from which the DNA derived were correspondingly allocated, in each species, to a small number of isochore families: five in human, four in mouse, six in chicken, and two in Xenopus.…”

Section: The Gene Landscapes Apparently Correspond To Experimentally mentioning

confidence: 99%

“…The number of peaks found in the human (five, or possibly six), mouse (four), chicken (six), and Xenopus landscapes (two) correspond to those that one might expect from the major components of bulk DNA. The latter were determined experimentally (Macaya et al 1976;Cortadas et al 1977;Cuny et al 1981) by silver-and BAMDassisted density gradient ultracentrifugation of DNA fragments ranging up to 50-100 kb. BAMD is an acronym for 3,6-bis (acetomercurimethyl) 1-4 dioxane, a mercury-based, sequence-specific DNA ligand that binds preferentially to AT-rich DNA, and that may also exhibit a preference for certain AT-rich oligonucleotides.…”

Section: The Gene Landscapes Apparently Correspond To Experimentally mentioning

confidence: 99%

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Compositional Gene Landscapes in Vertebrates

Cruveiller

Jabbari²,

Clay³

et al. 2004

Genome Res.

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The existence of a well conserved linear relationship between GC levels of genes' second and third codon positions (GC2, GC3) prompted us to focus on the landscape, or joint distribution, spanned by these two variables. In human, well curated coding sequences now cover at least 15%-30% of the estimated total gene set. Our analysis of the landscape defined by this gene set revealed not only the well documented linear crest, but also the presence of several peaks and valleys along that crest, a property that was also indicated in two other warm-blooded vertebrates represented by large gene databases, that is, mouse and chicken. GC2 is the sum of eight amino acid frequencies, whereas GC3 is linearly related to the GC level of the chromosomal region containing the gene. The landscapes therefore portray relations between proteins and the DNA environments of the genes that encode them.Two-dimensional frequency distributions of the GC levels of second and third codon positions of protein-coding genes reveal compositional constraints and selection pressures: those acting on proteins on one hand, and those acting on DNA, RNA, and possibly translational accuracy on the other hand. Indeed, GC levels in third positions (GC3) are almost free of constraints at the amino acid level, whereas those in second positions (GC2) are almost completely determined by the gene product. Their joint distribution, or landscape, therefore displays relations between the DNA and the proteins that its embedded genes encode.Among taxa that are well represented in sequence databases, genic GC2 and GC3 levels exhibit a tendency to cluster along a widely conserved, straight line in the landscape: the landscape's major axis or orthogonal regression line. The correlation to which this linearity corresponds is found in species as distant as human and Escherichia coli, and the major axis is consistently close to the line GC3 = 6 GC2 ‫מ‬ 200%. In other words, a 1% change in GC2 corresponds roughly to a 6% change in GC3, and the two codon positions have similar GC levels around 40%. The intragenomic correlation, and the correlation between first/ second and third codon positions (GC1 + 2 vs.

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The Genomic Code: A Pervasive Encoding/Molding of Chromatin Structures and a Solution of the “Non‐Coding DNA” Mystery

Bernardi

2019

BioEssays

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Recent investigations have revealed 1) that the isochores of the human genome group into two super-families characterized by two different long-range 3D structures, and 2) that these structures, essentially based on the distribution and topology of short sequences, mold primary chromatin domains (and define nucleosome binding). More specifically, GC-poor, gene-poor isochores are low-heterogeneity sequences with oligo-A spikes that mold the lamina-associated domains (LADs), whereas GC-rich, gene-rich isochores are characterized by single or multiple GC peaks that mold the topologically associating domains (TADs). The formation of these "primary TADs" may be followed by extrusion under the action of cohesin and CTCF. Finally, the genomic code, which is responsible for the pervasive encoding and molding of primary chromatin domains (LADs and primary TADs, namely the "gene spaces"/"spatial compartments") resolves the longstanding problems of "non-coding DNA," "junk DNA," and "selfish DNA" leading to a new vision of the genome as shaped by DNA sequences. and its role on the structure of the genome. This review deals exactly with this problem and shows, on the basis of past [4][5][6] and recent [7][8][9][10] published findings, that there is a fundamental link between DNA structure and chromatin structure, the "genomic code," which involves the encoding and molding of chromatin structure. Furthermore, being pervasive in the genome, the genomic code solves old outstanding problems, such as the "non-coding DNA," "junk DNA," or "selfish DNA."A good starting point for this introduction is to recall three early observations that are the roots of the recent findings because they concern DNA conformation and its link with the distribution of short sequences in the genome. This will be done not merely for historical reasons but because of their relevance to the recent results under review. Fifty five years ago, it was found [11] that calf thymus DNA undergoes a reversible decrease in viscosity in the sub-melting temperature range, indicating a reversible change in the configuration of ≈35% GCpoor DNA molecules. Five years later, two approaches, developed in order to fractionate DNAs on the basis of composition, provided information on their 3D conformation and their shortsequence frequencies. The background of the first approach was the chromatography of proteins on hydroxyapatite, a type of calcium phosphate, which had been shown to separate phosphoproteins according to their phosphate levels. [12] When applied to DNA, this approach separated native from denatured DNA, a "collapsed" structure that is eluted at a lower phosphate molarity because it has less phosphates available for binding to the calcium of hydroxyapatite. [13] In 1968, the discovery was made that hydroxyapatite could also separate yeast nuclear DNA (38% GC) from mitochondrial DNAs (18% GC in wild-type cells down to 4% GC in different "petite" mutants), the latter of which are eluted at increasingly higher phosphate molarities. This is because, being increasin...

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The Major Components of the Mouse and Human Genomes

Cited by 148 publications

References 48 publications

Organization of Nucleotide Sequences in the Chicken Genome

Organization of Nucleotide Sequences in the Chicken Genome

Compositional Gene Landscapes in Vertebrates

The Genomic Code: A Pervasive Encoding/Molding of Chromatin Structures and a Solution of the “Non‐Coding DNA” Mystery

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