7,966 research outputs found
Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution
It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing
Exons, introns and DNA thermodynamics
The genes of eukaryotes are characterized by protein coding fragments, the
exons, interrupted by introns, i.e. stretches of DNA which do not carry any
useful information for the protein synthesis. We have analyzed the melting
behavior of randomly selected human cDNA sequences obtained from the genomic
DNA by removing all introns. A clear correspondence is observed between exons
and melting domains. This finding may provide new insights in the physical
mechanisms underlying the evolution of genes.Comment: 4 pages, 8 figures - Final version as published. See also Phys. Rev.
Focus 15, story 1
DNA ANALYSIS USING GRAMMATICAL INFERENCE
An accurate language definition capable of distinguishing between coding and non-coding DNA has important applications and analytical significance to the field of computational biology. The method proposed here uses positive sample grammatical inference and statistical information to infer languages for coding DNA.
An algorithm is proposed for the searching of an optimal subset of input sequences for the inference of regular grammars by optimizing a relevant accuracy metric. The algorithm does not guarantee the finding of the optimal subset; however, testing shows improvement in accuracy and performance over the basis algorithm.
Testing shows that the accuracy of inferred languages for components of DNA are consistently accurate. By using the proposed algorithm languages are inferred for coding DNA with average conditional probability over 80%. This reveals that languages for components of DNA can be inferred and are useful independent of the process that created them. These languages can then be analyzed or used for other tasks in computational biology.
To illustrate potential applications of regular grammars for DNA components, an inferred language for exon sequences is applied as post processing to Hidden Markov exon prediction to reduce the number of wrong exons detected and improve the specificity of the model significantly
Copy number variants and selective sweeps in natural populations of the house mouse (Mus musculus domesticus)
Copy–number variants (CNVs) may play an important role in early adaptations, potentially facilitating rapid divergence of populations. We describe an approach to study this question by investigating CNVs present in natural populations of mice in the early stages of divergence and their involvement in selective sweeps. We have analyzed individuals from two recently diverged natural populations of the house mouse (Mus musculus domesticus) from Germany and France using custom, high–density, comparative genome hybridization arrays (CGH) that covered almost 164 Mb and 2444 genes. One thousand eight hundred and sixty one of those genes we previously identified as differentially expressed between these populations, while the expression of the remaining genes was invariant. In total, we identified 1868 CNVs across all 10 samples, 200 bp to 600 kb in size and affecting 424 genic regions. Roughly two thirds of all CNVs found were deletions. We found no enrichment of CNVs among the differentially expressed genes between the populations compared to the invariant ones, nor any meaningful correlation between CNVs and gene expression changes. Among the CNV genes, we found cellular component gene ontology categories of the synapse overrepresented among all the 2444 genes tested. To investigate potential adaptive significance of the CNV regions, we selected six that showed large differences in frequency of CNVs between the two populations and analyzed variation in at least two microsatellites surrounding the loci in a sample of 46 unrelated animals from the same populations collected in field trappings. We identified two loci with large differences in microsatellite heterozygosity (Sfi1 and Glo1/Dnahc8 regions) and one locus with low variation across the populations (Cmah), thus suggesting that these genomic regions might have recently undergone selective sweeps. Interestingly, the Glo1 CNV has previously been implicated in anxiety–like behavior in mice, suggesting a differential evolution of a behavioral trai
DNA Steganalysis Using Deep Recurrent Neural Networks
Recent advances in next-generation sequencing technologies have facilitated
the use of deoxyribonucleic acid (DNA) as a novel covert channels in
steganography. There are various methods that exist in other domains to detect
hidden messages in conventional covert channels. However, they have not been
applied to DNA steganography. The current most common detection approaches,
namely frequency analysis-based methods, often overlook important signals when
directly applied to DNA steganography because those methods depend on the
distribution of the number of sequence characters. To address this limitation,
we propose a general sequence learning-based DNA steganalysis framework. The
proposed approach learns the intrinsic distribution of coding and non-coding
sequences and detects hidden messages by exploiting distribution variations
after hiding these messages. Using deep recurrent neural networks (RNNs), our
framework identifies the distribution variations by using the classification
score to predict whether a sequence is to be a coding or non-coding sequence.
We compare our proposed method to various existing methods and biological
sequence analysis methods implemented on top of our framework. According to our
experimental results, our approach delivers a robust detection performance
compared to other tools
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Exploring the loblolly pine (Pinus taeda L.) genome by BAC sequencing and Cot analysis.
Loblolly pine (LP; Pinus taeda L.) is an economically and ecologically important tree in the southeastern U.S. To advance understanding of the loblolly pine (LP; Pinus taeda L.) genome, we sequenced and analyzed 100 BAC clones and performed a Cot analysis. The Cot analysis indicates that the genome is composed of 57, 24, and 10% highly-repetitive, moderately-repetitive, and single/low-copy sequences, respectively (the remaining 9% of the genome is a combination of fold back and damaged DNA). Although single/low-copy DNA only accounts for 10% of the LP genome, the amount of single/low-copy DNA in LP is still 14 times the size of the Arabidopsis genome. Since gene numbers in LP are similar to those in Arabidopsis, much of the single/low-copy DNA of LP would appear to be composed of DNA that is both gene- and repeat-poor. Macroarrays prepared from a LP bacterial artificial chromosome (BAC) library were hybridized with probes designed from cell wall synthesis/wood development cDNAs, and 50 of the "targeted" clones were selected for further analysis. An additional 25 clones were selected because they contained few repeats, while 25 more clones were selected at random. The 100 BAC clones were Sanger sequenced and assembled. Of the targeted BACs, 80% contained all or part of the cDNA used to target them. One targeted BAC was found to contain fungal DNA and was eliminated from further analysis. Combinations of similarity-based and ab initio gene prediction approaches were utilized to identify and characterize potential coding regions in the 99 BACs containing LP DNA. From this analysis, we identified 154 gene models (GMs) representing both putative protein-coding genes and likely pseudogenes. Ten of the GMs (all of which were specifically targeted) had enough support to be classified as intact genes. Interestingly, the 154 GMs had statistically indistinguishable (α = 0.05) distributions in the targeted and random BAC clones (15.18 and 12.61 GM/Mb, respectively), whereas the low-repeat BACs contained significantly fewer GMs (7.08 GM/Mb). However, when GM length was considered, the targeted BACs had a significantly greater percentage of their length in GMs (3.26%) when compared to random (1.63%) and low-repeat (0.62%) BACs. The results of our study provide insight into LP evolution and inform ongoing efforts to produce a reference genome sequence for LP, while characterization of genes involved in cell wall production highlights carbon metabolism pathways that can be leveraged for increasing wood production
Exon-phase symmetry and intrinsic structural disorder promote modular evolution in the human genome
A key signature of module exchange in the genome is phase symmetry of exons, suggestive of exon shuffling events that occurred without disrupting translation reading frame. At the protein level, intrinsic structural disorder may be another key element because disordered regions often serve as functional elements that can be effectively integrated into a protein structure. Therefore, we asked whether exon-phase symmetry in the human genome and structural disorder in the human proteome are connected, signalling such evolutionary mechanisms in the assembly of multi-exon genes. We found an elevated level of structural disorder of regions encoded by symmetric exons and a preferred symmetry of exons encoding for mostly disordered regions (>70% predicted disorder). Alternatively spliced symmetric exons tend to correspond to the most disordered regions. The genes of mostly disordered proteins (>70% predicted disorder) tend to be assembled from symmetric exons, which often arise by internal tandem duplications. Preponderance of certain types of short motifs (e.g. SH3-binding motif) and domains (e.g. high-mobility group domains) suggests that certain disordered modules have been particularly effective in exon-shuffling events. Our observations suggest that structural disorder has facilitated modular assembly of complex genes in evolution of the human genome. © 2013 The Author(s)
Universal power law behaviors in genomic sequences and evolutionary models
We study the length distribution of a particular class of DNA sequences known
as 5'UTR exons. These exons belong to the messanger RNA of protein coding
genes, but they are not coding (they are located upstream of the coding portion
of the mRNA) and are thus less constrained from an evolutionary point of view.
We show that both in mouse and in human these exons show a very clean power law
decay in their length distribution and suggest a simple evolutionary model
which may explain this finding. We conjecture that this power law behaviour
could indeed be a general feature of higher eukaryotes.Comment: 15 pages, 3 figure
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