Compositional Gene Landscapes in Vertebrates

Abstract

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.

Chromosome Architecture and Genome Organization

“…Indeed, scanning base composition along the DNA sequences of human chromosomes revealed regions that 1) exhibit a fairly homogeneous base composition ([ 14 , 16 ]; see also S1 Table ); 2) range from 200 Kb to several megabases [ 14 , 16 ]; 3) fall into five families, L1, L2, H1, H2 and H3 ([ 9 ]; also supported by the multimodal distribution of coding sequences [ 17 ]); 4) are flanked by sequences showing higher or lower GC levels, that generally belong to the compositionally closest families, so forming an ordered compositional mosaic; and 5) correspond to the families originally detected by ultracentrifugation [ 6 , 14 , 16 ]. The five isochore families are characterized by 1) increasing GC levels and GC ranges and decreasing average sizes ([ 16 ]; see Fig 1B and S1 Table ); 2) different trinucleotide frequencies [ 18 , 19 ] and different nucleosome positioning patterns [ 20 ]; 3) increasing gene densities [ 21 ].…”

An isochore map of human chromosomes

“…This fact also explains why GC distributions of fixed-length fragments of the human genome (Lander et al 2001) do not show the local maxima observed here. Finally, the isochore families corresponded to peaks in "gene landscapes" (Cruvellier et al 2004), formed by the distribution of coding sequences according to the GC levels of second and third codon positions (GC 2 and GC 3 ).…”

Simple proteomic checks for detecting noncoding RNA

“…This principle is often overlooked, despite much attention to automating gene prediction. In previous work, we proposed a simple screen, and applied it to rice [3,4], based on a constraint that is experienced by protein-coding genes in species ranging from human to Escherichia coli. GC levels (guanine 1 cytosine %) are distinctly lower in second (GC2) than in third (GC3) codon positions.…”