Selection for ancient periodic motifs that do not impart DNA bending

A ~10–11 bp periodicity in dinucleotides imparting DNA bending, with shorter periods found in organisms with positively-supercoiled DNA and longer periods found in organisms with negatively-supercoiled DNA, was previously suggested to assist in DNA compaction. However, when measured with more robust methods, variation in the observed periods between organisms with different growth temperatures is not consistent with that hypothesis. We demonstrate that dinucleotide periodicity does not arise solely by mutational biases but is under selection. We found variation between genomes in both the period and the suite of dinucleotides that are periodic. Whereas organisms with similar growth temperatures have highly variable periods, differences in periods increase with phylogenetic distance between organisms. In addition, while the suites of dinucleotides under selection for periodicity become more dissimilar among more distantly-related organisms, there is a core set of dinucleotides that are strongly periodic among genomes in all domains of life. Notably, this core set of periodic motifs are not involved in DNA bending. These data indicate that dinucleotide periodicity is an ancient genomic architecture which may play a role in shaping the evolution of genes and genomes.Author summary: Chromosomes are DNA polymers comprising hundreds of millions of instances of 4 different nucleotide building blocks. Chromosomes are often viewed as repositories of genes, which are small DNA regions encoding products which cooperate to make an organism. But chromosomes are also enormous, unwieldy molecules that must be maneuvered in various ways. Due to their bulk, maneuverability would be greatly facilitated by information embedded within and between genes which assists those processes. This infrastructure would enable cells to manipulate genomes efficiently; disrupting it would be disastrous. We examined the spacings between all possible pairs of nucleotides (dinucleotides) and found that different dinucleotides were strongly periodic in different organisms. That is, certain spacings were more frequently observed, and were integral multiples of a single spacing (the period). The period varied among organisms between 9.7 and 11.8 nucleotides; contrary to long-held assumptions, the period was not related to organismal growth temperature. More closely-related organisms were more likely to have similar periods and share which dinucleotides were periodic, but even distantly-related organisms shared a core of periodic dinucleotides. This ancient periodicity likely assists cells in maneuvering the vast DNA polymer, and differences between organisms could restrict the flow of genes between them.