Periodic spacing of A-tracts (short runs of A or T) with the DNA helical period of ~10–11 bp is associated with intrinsic DNA curvature [1, 2]. In eukaryotes, this periodicity is a major component of the nucleosome positioning signal [1, 3–7]. The DNA sequence periodicity can influence properties of the chromatin and expression of the encoded genes. For example, the “hyperperiodic regions” of the Caenorhabditis elegans genome are subject to particular types of histone modifications and contain mostly germ-line specific genes [8–10].
Strong periodic patterns with the characteristic period of ~10–11 bp were also detected in many prokaryotic genomes [9, 11–16]. The biological role of the sequence periodicity and DNA curvature in prokaryotes is not clear, although several possible roles or causes of the 10–11 bp periodicity have been proposed. Zhurkin pointed out that a similar periodic signal can arise from amphipathic α-helices in proteins . α-helices feature a helical period of about 3.6 residues per turn, which in DNA translates to an ~10.8 bp period. However, presence of the periodic patterns in both protein-coding and noncoding regions, as well as the extent of the periodicity beyond distances typical of α-helix lengths suggest that the sequence periodicity related to α-helices in proteins is not the only cause of the observed strong periodic signal in prokaryotic DNA [11, 12]. DNA bending affects DNA-protein interactions and curved DNA segments are often associated with promoters, where they can influence interactions between DNA and transcription factors [18, 19]. The sequence periodicity could also promote a particular mode of supercoiling: Herzel and coworkers proposed that ~11 bp periodicity found in most bacteria can relate to predominant negative supercoiling whereas ~10 bp periodicity of some archaeal genomes could promote positive supercoiling [9, 13]. Tolstorukov and coworkers analyzed clusters of periodically spaced. A-tracts in E. coli and other bacterial genomes, and proffered a hypothesis that the sequence periodicity-driven intrinsically curved segments contribute to the formation and stability of supercoiled DNA loops that constitute bacterial nucleoid . It is possible that the DNA sequence periodicity in prokaryotes can play multiple roles, including facilitating transcription initiation, contributing to DNA folding in the nucleoid, and promoting positive or negative supercoiling, but most likely to different extent in different genomes.
Whereas earlier works focused on measuring the predominant period in a whole genome, we recently developed a technique that allows comparing the intensity of the periodic signal among different genomes or different regions of the same genome . Comparisons among more than 1000 prokaryotic chromosomes revealed major differences in the intensity of the periodic signal among different genomes as well as varying levels of intrachromosomal heterogeneity . In most prokaryotic chromosomes, a strong DNA curvature-related periodicity is restricted to short chromosomal segments. By contrast, some genomes feature a persistently strong periodic signal covering majority of the chromosome length. Finally, some genomes exhibit hardly any periodic signal at all. We attributed the differences to presumed organism-specific differences in nucleoid structure and also noted that intrachromosomal heterogeneity could be related to differences in gene expression in different sections of the chromosome . We now extended the analysis of DNA curvature-related sequence periodicity in prokaryotes to large bacteriophages. Comparisons with chromosomal DNA indicate that phages generally lack a strong periodic signal. Moreover, chromosomes that contain prophages tend to have weaker or less persistent sequence periodicity, suggesting that the periodicity and concomitant DNA curvature could also play a role in protecting the chromosome from phage integration.