Comparative Analysis of Sequence Periodicity among Prokaryotic Genomes Points to Differences in Nucleoid Structure and a Relationship to Gene Expression

Abstract

ABSTRACT Regular spacing of short runs of A or T nucleotides in DNA sequences with a period close to the helical period of the DNA double helix has been associated with intrinsic DNA bending and nucleosome positioning in eukaryotes. Analogous periodic signals were also observed in prokaryotic genomes. While the exact role of this periodicity in prokaryotes is not known, it has been proposed to facilitate the DNA packaging in the prokaryotic nucleoid and/or to promote negative or positive supercoiling. We developed a methodology for assessments of intragenomic heterogeneity of these periodic patterns and applied it in analysis of 1,025 prokaryotic chromosomes. This technique allows more detailed analysis of sequence periodicity than previous methods where sequence periodicity was assessed in an integral form across the whole chromosome. We found that most genomes have the periodic signal confined to several chromosomal segments while most of the chromosome lacks a strong sequence periodicity. Moreover, there are significant differences among different prokaryotes in both the intensity and persistency of sequence periodicity related to DNA curvature. We proffer that the prokaryotic nucleoid consists of relatively rigid sections stabilized by short intrinsically bent DNA segments and characterized by locally strong periodic patterns alternating with regions featuring a weak periodic signal, which presumably permits higher structural flexibility. This model applies to most bacteria and archaea. In genomes with an exceptionally persistent periodic signal, highly expressed genes tend to concentrate in aperiodic sections, suggesting that structural heterogeneity of the nucleoid is related to local differences in transcriptional activity.