The coexistence of the nucleosome positioning code with the genetic code on eukaryotic genomes

It is known that there are several codes residing simultaneously on the DNA double helix. The two best-characterized codes are the genetic code—the code for protein production, and the code for DNA packaging into nucleosomes. Since these codes have to coexist simultaneously on the same DNA region, both must be degenerate to allow this coexistence. A-tracts are homopolymeric stretches of several adjacent deoxyadenosines on one strand of the double helix, having unusual structural properties, which were shown to exclude nucleosomes and as such are instrumental in setting the translational positioning of DNA within nucleosomes. We observe, cross-kingdoms, a strong codon bias toward the avoidance of long A-tracts in exon regions, which enables the formation of high density of nucleosomes in these regions. Moreover, long A-tract avoidance is restricted exclusively to nucleosome-occupied exon regions. We show that this bias in codon usage is sufficient for enabling DNA organization within nucleosomes without constraints on the actual code for proteins. Thus, there is inter-dependency of the two major codes within DNA to allow their coexistence. Furthermore, we show that modulation of A-tract occurrences in exon versus non-exon regions may result in a unique alternation of the diameter of the ‘30-nm’ fiber model.