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1.
DNA sequences contain information about the bendability and native conformation of DNA. For example, a repetition of certain dinucleotides at distances of 10-11bp supports wrapping around nucleosomes and supercoiled structures of bacterial DNA. We analyzed 86 eubacterial genomes, 16 archaea, and six genomes of higher eukaryotes. First, we discuss whether or not the observed periodicities represent indeed bendability signals. This claim is confirmed since: (1) dinucleotide signals are of comparable size to mononucleotide signals, (2) the signals are present in non-coding DNA as well, and (3) repeat masking has only a minor effect on 10-11bp periodicities. Moreover, the periodicities persist up to 150bp, comparable to the nucleosome size. We show that doublet peaks in Caenorhabditis elegans and some prokaryotes can be traced back to long-ranging modulations. In mammalian genomes, we find consistently spectral peaks as observed earlier in human chromosomes 20, 21 and 22. It has been shown in previous studies that archaea have periods of 10bp, whereas eubacteria exhibit 11bp periodicities. These differences reflect different supercoiled states of microbial DNA. Is the period of 10bp an archaeal or a thermophilic feature? This question is addressed by relating periodicities to optimal growth temperatures. It turns out that the archaea Methanopyrus kandleri (t(opt)=80 degrees C) and a Halobacterium strain (t(opt)=42 degrees C) both have longer periods of about 11bp. Eubacterial genomes have consistently periods around 11bp indicative of negative supercoiling.  相似文献   

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Liu H  Wu J  Xie J  Yang X  Lu Z  Sun X 《Biophysical journal》2008,94(12):4597-4604
By analyzing dinucleotide position-frequency data of yeast nucleosome-bound DNA sequences, dinucleotide periodicities of core DNA sequences were investigated. Within frequency domains, weakly bound dinucleotides (AA, AT, and the combinations AA-TT-TA and AA-TT-TA-AT) present doublet peaks in a periodicity range of 10-11 bp, and strongly bound dinucleotides present a single peak. A time-frequency analysis, based on wavelet transformation, indicated that weakly bound dinucleotides of core DNA sequences were spaced smaller (∼10.3 bp) at the two ends, with larger (∼11.1 bp) spacing in the middle section. The finding was supported by DNA curvature and was prevalent in all core DNA sequences. Therefore, three approaches were developed to predict nucleosome positions. After analyzing a 2200-bp DNA sequence, results indicated that the predictions were feasible; areas near protein-DNA binding sites resulted in periodicity profiles with irregular signals. The effects of five dinucleotide patterns were evaluated, indicating that the AA-TT pattern exhibited better performance. A chromosome-scale prediction demonstrated that periodicity profiles perform better than previously described, with up to 59% accuracy. Based on predictions, nucleosome distributions near the beginning and end of open reading frames were analyzed. Results indicated that the majority of open reading frames’ start and end sites were occupied by nucleosomes.  相似文献   

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Merling A  Sagaydakova N  Haran TE 《Biochemistry》2003,42(17):4978-4984
It is well-known, but little understood, that the nucleotide sequences between phased A(4-6)-tracts (at 10-11 bp intervals) have only a slight effect on overall curvature. To explore this phenomenon, we have examined the gel-migration properties of sequences containing both A-tracts as well as G-tracts (i.e., sequences of the form G(n)C(m) or C(n)G(m), n + m > 4) in various relative positioning. We show that the composite bend of these sequences depends on their relative arrangement. When G-tracts are placed between two A-tracts, such that both tracts are repeated in phase to themselves (e.g., G(5)A(6)G(5)A(5)), or adjacent to the 3'-side of A-tracts (e.g., A(6)G(5)N(10)), they have minimal influence on the extent of bending of the composite sequence. When G-tracts are placed one helical repeat away from A-tracts (e.g., G(5)N(5)A(6)N(6)), or are adjacent only to the 5'-side of A-tracts (e.g., G(5)A(6)N(10)) their influence on the composite bend is larger. The differential behavior of AG- versus GA-tracts means that A-tracts influence their flanking sequences in a polar manner. Whereas they suppress, or make constant, the intrinsic bending characteristics of any sequence placed immediately 3' to them (and hence by definition any sequence placed between two phased A-tracts), sequences adjoining them on their 5'-side are free to modulate the overall curvature. We interpret these results as evidence for the dominant nature of the unique and nonuniform structure adopted by tracts of four adenines or more. The effects of A-tracts extend at least five base pairs into the adjoining 3' region. This is further evidence for the complexity of DNA structure and the inadequacy of simple nearest-neighbor models to explain all its manifestations.  相似文献   

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Computer analyses of various genome sequences revealed the existence of certain periodical patterns of adenine–adenine dinucleotides (ApA). For each genome sequence of 13 eubacteria, 3 archaebacteria, 10 eukaryotes, 60 mitochondria, and 9 chloroplasts, we counted frequencies of ApA dinucleotides at each downstream position within 50 bp from every ApA. We found that the complete genomes of all three archaebacteria have clear ApA periodicities of about 10 bps. On the other hand, all of the 13 eubacteria we analyzed were found to have an ApA periodicity of about 11 bp. Similar periodicities exist in the 10 eukaryotes, although higher organisms such as primates tend to have weaker periodic patterns. None of the mitochondria and chroloplasts we analyzed showed an evident periodic pattern. Received: 3 November 1998 / Accepted: 24 March 1999  相似文献   

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We determined DNA bend sites in the promoter region of the human estrogen receptor (ER) gene by the circular permutation assay. A total of five sites (ERB-4 to -1, and ERB+1) mapped in the 3 kb region showed an average distance of 688 bp. Most of the sites were accompanied by short poly(dA) x poly(dT) tracts including the potential bend core sequence A2N8A2N8A2 (A/A/A). Fine mapping of the ERB-2 site indicated that this A/A/A and the 20 bp immediate flanking sequence containing one half of the estrogen response element were the sites of DNA curvature. All of the experimentally mapped bend sites corresponded to the positions of DNA curvature as well as to nucleosomes predicted by computer analysis. In vitro nucleosome mapping at ERB-2 revealed that the bend center was located 10-30 bp from the experimental and predicted nucleosome dyad axes.  相似文献   

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Background

Periodic spacing of A-tracts (short runs of A or T) with the DNA helical period of ~10?C11?bp is characteristic of intrinsically bent DNA. In eukaryotes, the DNA bending is related to chromatin structure and nucleosome positioning. However, the physiological role of strong sequence periodicity detected in many prokaryotic genomes is not clear.

Results

We developed measures of intensity and persistency of DNA curvature-related sequence periodicity and applied them to prokaryotic chromosomes and phages. The results indicate that strong periodic signals present in chromosomes are generally absent in phage genomes. Moreover, chromosomes containing prophages are less likely to possess a persistent periodic signal than chromosomes with no prophages.

Conclusions

Absence of DNA curvature-related sequence periodicity in phages could arise from constraints associated with DNA packaging in the viral capsid. Lack of prophages in chromosomes with persistent periodic signal suggests that the sequence periodicity and concomitant DNA curvature could play a role in protecting the chromosomes from integration of phage DNA.  相似文献   

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Wang JP  Widom J 《Nucleic acids research》2005,33(21):6743-6755
DNA sequences that are present in nucleosomes have a preferential approximately 10 bp periodicity of certain dinucleotide signals, but the overall sequence similarity of the nucleosomal DNA is weak, and traditional multiple sequence alignment tools fail to yield meaningful alignments. We develop a mixture model that characterizes the known dinucleotide periodicity probabilistically to improve the alignment of nucleosomal DNAs. We assume that a periodic dinucleotide signal of any type emits according to a probability distribution around a series of 'hot spots' that are equally spaced along nucleosomal DNA with 10 bp period, but with a 1 bp phase shift across the middle of the nucleosome. We model the three statistically most significant dinucleotide signals, AA/TT, GC and TA, simultaneously, while allowing phase shifts between the signals. The alignment is obtained by maximizing the likelihood of both Watson and Crick strands simultaneously. The resulting alignment of 177 chicken nucleosomal DNA sequences revealed that all 10 distinct dinucleotides are periodic, however, with only two distinct phases and varying intensity. By Fourier analysis, we show that our new alignment has enhanced periodicity and sequence identity compared with center alignment. The significance of the nucleosomal DNA sequence alignment is evaluated by comparing it with that obtained using the same model on non-nucleosomal sequences.  相似文献   

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Fukushima A  Ikemura T  Kinouchi M  Oshima T  Kudo Y  Mori H  Kanaya S 《Gene》2002,300(1-2):203-211
We used a power spectrum method to identify periodic patterns in nucleotide sequence, and characterized nucleotide sequences that confer periodicities to prokaryotic and eukaryotic genomes and genomes. A 10-bp periodicity was prevalent in hyperthermophilic bacteria and archaebacteria, and an 11-bp periodicity was prevalent in eubacteria. The 10-bp periodicity was also prevalent in the eukaryotes such as the worm Caenorhabditis elegans. Additionally, in the worm genome, a 68-bp periodicity in chromosome I, a 59-bp periodicity in chromosome II, and a 94-bp periodicity in chromosome III were found. In human chromosomes 21 and 22, approximately 167- or 84-bp periodicity was detected along the entire length of these chromosomes. Because the 167-bp is identical to the length of DNA that forms two complete helical turns in nucleosome organization, we speculated that the respective sequences may correspond to arrays of a special compact form of nucleosomes clustered in specific regions of the human chromosomes. This periodic element contained a high frequency of TGG. TGG-rich sequences are known to form a specific subset of folded DNA structures, and therefore, the sequences might have potential to form specific higher order structures related to the clustered occurrence of a specific form of the speculated nucleosomes.  相似文献   

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The hybridization of human DNA with three non-cross-hybridizing monomers (68 bp in length) of the heterochromatic Sau3A family of DNA repeats, indicates the coexistence within a Sau3A-positive genomic block of divergent Sau3A units as well as of unrelated sequences. To gain some insight into the structure of these human heterochromatic DNA regions, three previously cloned Sau3A-positive genomic fragments (with a total length of approximately 1900 base-pairs (bp] were sequenced. The analysis of the sequences showed the presence of clustered Sau3A units with different degrees of divergence and of two DNA regions of approximately 100 bp and 291 bp in length, unrelated to the family of repeats. A consensus sequence derived from the 24 identified Sau3A monomers presents, among highly variable regions, two less variant regions of 8 bp and 10 bp in length, respectively. The Sau3A-unrelated DNA fragment 291 bp in length, used as a probe on genomic DNA digested with a series of restriction enzymes, defines a "new" family of DNA repeats possessing periodicities for HaeIII (HaeIII family). Sau3A and HaeIII repeats display a high degree of linkage in a collection of Sau3A-positive genomic recombinant phages.  相似文献   

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Two different views have been proposed for origins of genes (or proteins). One is that primordial genes evolved from random sequences. This view underlies the concept of modern in vitro evolution experiments that functional molecules (even proteins) evolved from random sequence-libraries. On the contrary, the second view reminds that "random sequences" would be an unusual state in which to find RNA or DNA, because it is their inherent nature to yield periodic structures during the course of semi-conservative replication. In this second view, the periodicity of DNA (or RNA) is responsible for emergence of primordial genes. Although recent reports on the variety of periodicities present in proteins, genes and genomes are consistent with the second view, it has yet to be experimentally tested. We assessed the significance of periodicities of DNA in the origin of genes by constructing such periodic DNAs. The results showed that periodic DNA produced ordered proteins at very high rates, which is in contrast to the fact that proteins with random sequences lack secondary structures. We concluded that periodicity played a pivotal role in the origin of many genes. The observation should pave the way for new experimental evolution systems for proteins.  相似文献   

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The recently published complete DNA sequence of the bacterium Thermotoga maritima provides evidence, based on protein sequence conservation, for lateral gene transfer between Archaea and Bacteria. We introduce a new method of periodicity analysis of DNA sequences, based on structural parameters, which brings independent evidence for the lateral gene transfer in the genome of T.maritima. The structural analysis relates the Archaea-like DNA sequences to the genome of Pyrococcus horikoshii. Analysis of 24 complete genomic DNA sequences shows different periodicity patterns for organisms of different origin. The typical genomic periodicity for Bacteria is 11 bp whilst it is 10 bp for Archaea. Eukaryotes have more complex spectra but the dominant period in the yeast Saccharomyces cerevisiae is 10.2 bp. These periodicities are most likely reflective of differences in chromatin structure.  相似文献   

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An estimated 80% of genomic DNA in eukaryotes is packaged as nucleosomes, which, together with the remaining interstitial linker regions, generate higher order chromatin structures [1]. Nucleosome sequences isolated from diverse organisms exhibit ∼10 bp periodic variations in AA, TT and GC dinucleotide frequencies. These sequence elements generate intrinsically curved DNA and help establish the histone-DNA interface. We investigated an important unanswered question concerning the interplay between chromatin organization and genome evolution: do the DNA sequence preferences inherent to the highly conserved histone core exert detectable natural selection on genomic divergence and polymorphism? To address this hypothesis, we isolated nucleosomal DNA sequences from Drosophila melanogaster embryos and examined the underlying genomic variation within and between species. We found that divergence along the D. melanogaster lineage is periodic across nucleosome regions with base changes following preferred nucleotides, providing new evidence for systematic evolutionary forces in the generation and maintenance of nucleosome-associated dinucleotide periodicities. Further, Single Nucleotide Polymorphism (SNP) frequency spectra show striking periodicities across nucleosomal regions, paralleling divergence patterns. Preferred alleles occur at higher frequencies in natural populations, consistent with a central role for natural selection. These patterns are stronger for nucleosomes in introns than in intergenic regions, suggesting selection is stronger in transcribed regions where nucleosomes undergo more displacement, remodeling and functional modification. In addition, we observe a large-scale (∼180 bp) periodic enrichment of AA/TT dinucleotides associated with nucleosome occupancy, while GC dinucleotide frequency peaks in linker regions. Divergence and polymorphism data also support a role for natural selection in the generation and maintenance of these super-nucleosomal patterns. Our results demonstrate that nucleosome-associated sequence periodicities are under selective pressure, implying that structural interactions between nucleosomes and DNA sequence shape sequence evolution, particularly in introns.  相似文献   

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Detection, sequence patterns and function of unusual DNA structures.   总被引:25,自引:14,他引:11       下载免费PDF全文
Unusual DNA structures were detected by an electrophoretic procedure in which DNA fragments were separated according to size on agarose gels and then by shape on polyacrylamide gels. Fragments from yeast centromeres migrated faster in polyacrylamide than predicted from their base composition and size and this property was attributed to a nonrandom distribution of oligomeric A tracts that exhibited minima at 10-11 base intervals. Fragments from seven loci in 107 kb of DNA migrated anomalously slow and these fragments contained blocks of A2-6 in a 10-11 base periodicity which is indicative of bent DNA. The most pronounced bent sequences were found within yeast ARS1 and centered at 245 and 240 bp from the left and right ends of the adenovirus genome. Each sequence is approximately 150 bp away from a replication origin and the adenovirus sequences are within 50 bp of enhancers. Nuclear matrix attachment sites, which are also adjacent to enhancers, contain sequences characteristic of bent DNA. These results suggest that bent structures reside at the base of DNA loops in chromosomes.  相似文献   

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A unique deletion covering around 43% of the pBR322 genome was found after attempting to insert 100 or 200 bp poly(dA).poly(dT) into the EcoRV site of pBR322 DNA. This result was not observed if an equivalent size heterologous DNA or a larger poly(dA).poly(dT) fragment of 10-20,000 bp was introduced at the same site. DNA sequencing analysis at the junctions suggests that a specific intramolecular pairing may be involved in the formation of this deletion mutant.  相似文献   

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