Sequence periodicity of Escherichia coli is concentrated in intergenic regions
© Hosid et al; licensee BioMed Central Ltd. 2004
Received: 31 December 2003
Accepted: 26 August 2004
Published: 26 August 2004
Sequence periodicity with a period close to the DNA helical repeat is a very basic genomic property. This genomic feature was demonstrated for many prokaryotic genomes. The Escherichia coli sequences display the period close to 11 base pairs.
Here we demonstrate that practically only ApA/TpT dinucleotides contribute to overall dinucleotide periodicity in Escherichia coli. The noncoding sequences reveal this periodicity much more prominently compared to protein-coding sequences. The sequence periodicity of ApC/GpT, ApT and GpC dinucleotides along the Escherichia coli K-12 is found to be located as well mainly within the intergenic regions.
The observed concentration of the dinucleotide sequence periodicity in the intergenic regions of E. coli suggests that the periodicity is a typical property of prokaryotic intergenic regions. We suppose that this preferential distribution of dinucleotide periodicity serves many biological functions; first of all, the regulation of transcription.
DNA sequence periodicity with the period about 10–11 base pairs (bp) has been long known in eukaryotic DNA sequences. It was discovered recently in prokaryotic sequences as well [1–6]. The periodicity in Eubacteria sequences usually shows the period close to 11 bp . This period is clearly different from the structural helical period of 10.5–10.6 bp/turn [7, 8]. The difference was interpreted [1, 2] as a possible reflection of the sequence dependent writhe of prokaryotic DNA. In the work  it was demonstrated that the periodicity in the bacterial genomes, in E. coli as well, is distributed in a non-uniform way, in scattered segments of the size 100–150 bases. It was also known for a long time that quite a few DNA promoter regions of E. coli possess the sequence periodicity of AA and TT dinucleotides .
The sequence periodicity of AA/TT dinucleotides is frequently associated with sequence-dependent DNA curvature, which is known to play an important role in the initiation of transcription of many genes (for reviews, see [11–15]). Using different models and approaches for prediction of intrinsic DNA curvature it was shown that many E. coli promoters have upstream curved sequences [16, 17]. Pedersen et al.  showed that promoter area frequently has an unusual sequence structure. This region possesses higher DNA curvature, more rigid and less stable. Moreover, in our study of prokaryotic terminators of transcription (Hosid and Bolshoy, submitted) we have found that in E. coli DNA curvature peaks are frequently located downstream of the CDS.
Since the dinucleotide periodicity with the period close to the helical repeat is associated with DNA intrinsic curvature [19–23], the curvature distribution along DNA would suggest similar distribution of DNA sequence periodicity.
In this work, the sequence dinucleotide periodicity in E. coli and its distribution along the genome are systematically analyzed. A strong preference of intergenic regions to express the sequence periodicity of AA, AC, GC, and TT dinucleotides is discovered.
Results and Discussion
To screen the genome of E. coli and find out where the periodical regions are located, we chose the period 11.2 bp [1, 2, 5] and this study (Fig. 1); and the window of 150 bp [9, 26]. We used periodical AA and TT probes with the above periodicity to correlate with the E. coli genome sequence and to detect the periodical sites. This calculation shows that the periodicity is not evenly distributed along the E. coli genome.
The spectral analysis (Fig. 1) and examples of the periodicity distribution maps (Fig. 2) show that apart from described correlation among the intergenic regions and AA/TT periodicity, there are numerous sites of periodicity located within coding sequences. Work is in progress to find out the functional relevance, if any, of these sites.
The observed concentration of the sequence periodicity in the intergenic regions corroborates earlier results and suggests that the periodicity is a typical property of the intergenic regions.
The sequence of the whole genome of Escherichia coli K-12 MG1655, locus U00096, 4639221 base pairs, was taken from the National Center of Biotechnology Information ftp://ftp.ncbi.nih.gov/genbank/genomes. Intergenic regions were identified in accordance with the annotation to this genome of E. coli and gathered in a separate dataset.
Fourier transform of positional autocorrelation function
Autocorrelation profile X was calculated for each dinucleotide separately. For the calculation of ApA autocorrelation, for example, we calculated the number of occurrences of pairs ApA – ApA in a distance k, and designated it by X k . Spectral analysis of autocorrelation profile X was obtained using the following formulae:
where f p is normalized wave-function amplitude of period p, X is an autocorrelation profile for one chosen dinucleotide, X i is its value in position i, is its average value, and W is a maximal considered autocorrelation distance (in our case 100 bp).
As a probe of periodicity the sine waves with period T were taken to describe idealized periodical distribution of AA and TT dinucleotides within window W. The probes were correlated with E. coli sequences by moving the probes along the sequences and calculating the value C for every position.
where i is an index of a dinucleotide position in the window W and
The value Cmax is introduced for the normalization purposes. It is calculated as follows:
where i is a position in the window W and
Ideally periodical sequence segments would be, therefore, described by C = 1, while segments with no periodicity would correspond to C = 0. The results of these calculations are presented as maps of the sequence periodicity. The four sample maps are shown in Fig. 2a,2b,2c,2d.
Synchronization of the maps
The maps around intergenic regions were combined (summed) separately for the groups of similar sizes of the intergenic regions. Five such groups were analyzed: 100 ± 50 bp, 200 ± 50 bp, 300 ± 50 bp, 400 ± 50 bp, and 500 ± 50 bp. For each group the maps were synchronized at the respective intergenic centers and the sums of the maps were calculated and smoothed by a running average within 51 bp. The standard deviations for the combined plots were estimated by generating random sequences of the same size and dinucleotides composition for each group separately and averaging the respective periodicity maps.
The resonance plot
The resonance 3D plot for the intergenic regions of length 200 ± 50 bp was built from calculations with different periods T in the interval 10–12.5 bp. One-third (202) of the most periodic maps of this group was taken for the calculation. The maps for different periods T were smoothed five times by a running average over 51 bp. The baselines were set to 0. The surface of 3D plot was smoothed 3 times by a running average over 9 point square elements, on the grid with separations 0.1 bp for T, and 20 bp for sequence position.
We thank V. Kirzhner and all members of the Genome Diversity Center for fruitful discussions and critical comments on the paper. A.B. is grateful to Professors T. Ratiu and J.H. Maddocks from the Bernoulli Institute at the Swiss Federal Institute of Technology for the kind invitation to visit "Centre Bernoulli" for two months. S.H. and A.B. are partially supported by the FIRST Foundation of the Israel Academy of Science and Humanities.
- Herzel H, Weiss O, Trifonov EN: Sequence periodicity in complete genomes of Archaea suggests positive supercoiling. J Biomol Struct Dyn. 1998, 16: 341-345.View ArticlePubMedGoogle Scholar
- Herzel H, Weiss O, Trifonov EN: 10–11 bp periodicities in complete genomes reflect protein structure and DNA folding. Bioinformatics. 1999, 15: 187-193. 10.1093/bioinformatics/15.3.187View ArticlePubMedGoogle Scholar
- Ozoline ON, Deev AA, Trifonov EN: DNA bendability – a novel feature in E-coli promoter recognition. J Biomol Struct Dyn. 1999, 16: 825-831.View ArticlePubMedGoogle Scholar
- Tomita M, Wada M, Kawashima Y: ApA dinucleotide periodicity in prokaryote, eukaryote, and organelle genomes. J Mol Evol. 1999, 49: 182-192.View ArticlePubMedGoogle Scholar
- Worning P, Jensen LJ, Nelson KE, Brunak S, Ussery DW: Structural analysis of DNA sequence: evidence for lateral gene transfer in Thermotoga maritima. Nucleic Acids Res. 2000, 28: 706-709. 10.1093/nar/28.3.706PubMed CentralView ArticlePubMedGoogle Scholar
- Petersen L, Larsen TS, Ussery DW, On SLW, Krogh A: RpoD promoters in Campylobacter jejuni exhibit a strong periodic signal instead of a-35 box. J Mol Biol. 2003, 326: 1361-1372. 10.1016/S0022-2836(03)00034-2View ArticlePubMedGoogle Scholar
- Strauss F, Gaillard C, Prunell A: Helical Periodicity of DNA, Poly(Da) . Poly(Dt) and Poly(Da-Dt) . Poly(Da-Dt) in Solution. Eur J Biochem. 1981, 118: 215-222.View ArticlePubMedGoogle Scholar
- Peck LJ, Wang JC: Sequence Dependence of the Helical Repeat of DNA in Solution. Nature. 1981, 292: 375-378.View ArticlePubMedGoogle Scholar
- Tolstorukov MY, Virnik K, Adhya S, Zhurkin VB: Genome-wide A-tract distribution and DNA packaging in pro-and eukaryotes [abstract]. J Biomol Struct Dyn. 2003, 20: 869-870.Google Scholar
- Plaskon RR, Wartell RM: Sequence Distributions Associated with DNA Curvature Are Found Upstream of Strong Escherichia-Coli Promoters. Nucleic Acids Res. 1987, 15: 785-796.PubMed CentralView ArticlePubMedGoogle Scholar
- Trifonov EN: Curved DNA. Crc Critical Reviews in Biochemistry. 1985, 19: 89-106.View ArticlePubMedGoogle Scholar
- Hagerman PJ: Sequence-directed curvature of DNA. Annu Rev Biochem. 1990, 59: 755-781. 10.1146/annurev.bi.59.070190.003543View ArticlePubMedGoogle Scholar
- Harrington RE: DNA Curving and Bending in Protein DNA Recognition. Mol Microbiol. 1992, 6 (18): 2549-2555.View ArticlePubMedGoogle Scholar
- Perez-Martin J, Rojo F, de Lorenzo V: Promoters responsive to DNA bending: a common theme in prokaryotic gene expression. Microbiol Rev. 1994, 58: 268-290.PubMed CentralPubMedGoogle Scholar
- Gabrielian A, Pongor S: Correlation of intrinsic DNA curvature with DNA property periodicity. FEBS Lett. 1996, 393: 65-68. 10.1016/0014-5793(96)00855-1View ArticlePubMedGoogle Scholar
- Lisser S, Margalit H: Determination of Common Structural Features in Escherichia-Coli Promoters by Computer-Analysis. Eur J Biochem. 1994, 223: 823-830.View ArticlePubMedGoogle Scholar
- Gabrielian AE, Landsman D, Bolshoy A: Curved DNA in promoter sequences. In Silico Biol. 2000, 1: 183-196.Google Scholar
- Pedersen AG, Jensen LJ, Brunak S, Staerfeldt HH, Ussery DW: A DNA structural atlas for Escherichia coli. J Mol Biol. 2000, 299: 907-930. 10.1006/jmbi.2000.3787View ArticlePubMedGoogle Scholar
- Marini JC, Levene SD, Crothers DM, Englund PT: Bent Helical Structure in Kinetoplast DNA. Proc Natl Acad Sci U S A. 1982, 79 (24): 7664-7668.PubMed CentralView ArticlePubMedGoogle Scholar
- Hagerman PJ: Evidence for the existence of stable curvature of DNA in solution. Proc Natl Acad Sci U S A. 1984, 81 (15): 4632-4636.PubMed CentralView ArticlePubMedGoogle Scholar
- Hagerman PJ: Sequence dependence of the curvature of DNA – a test of the phasing hypothesis. Biochemistry. 1985, 24 (25): 7033-7037.View ArticlePubMedGoogle Scholar
- Koo HS, Wu HM, Crothers DM: DNA bending at adenine . thymine tracts. Nature. 1986, 320 (6062): 501-506.View ArticlePubMedGoogle Scholar
- Ulanovsky L, Bodner M, Trifonov EN, Choder M: Curved DNA – Design, Synthesis, and Circularization. Proc Natl Acad Sci U S A. 1986, 83: 862-866.PubMed CentralView ArticlePubMedGoogle Scholar
- Trifonov EN: Translation Framing Code and Frame-Monitoring Mechanism as Suggested by the Analysis of Messenger-RNA and 16 S Ribosomal-RNA Nucleotide-Sequences. J Mol Biol. 1987, 194: 643-652.View ArticlePubMedGoogle Scholar
- Trifonov EN: 3-, 10.5-, 200-and 400-base periodicities in genome sequences. Physica A. 1998, 249: 511-516. 10.1016/S0378-4371(97)00510-4. 10.1016/S0378-4371(97)00510-4View ArticleGoogle Scholar
- Bolshoy A, Nevo E: Ecologic genomics of DNA: upstream bending in prokaryotic promoters. Genome Res. 2000, 10: 1185-1193. 10.1101/gr.10.8.1185PubMed CentralView ArticlePubMedGoogle Scholar
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