An analysis of symmetric words in human DNA: adjacent vs non-adjacent word distances

It is important to develop methods for nding DNA sites with high potencial for the formation of hairpin/cruciform structures. In a previous work, we studied the distances between adjacent reversed complement words (symmetric words), and we observed that for some words some distances were favored. In the work presented here, we extended the study to the distance between non-adjacent reversed complement words and we observed strong periodicity in the distance distribution of some words. This may be an indication of potential for the formation of hairpin/cruciform structures.publishe

It Is NL-complete to Decide Whether a Hairpin Completion of Regular Languages Is Regular

The hairpin completion is an operation on formal languages which is inspired by the hairpin formation in biochemistry. Hairpin formations occur naturally within DNA-computing. It has been known that the hairpin completion of a regular language is linear context-free, but not regular, in general. However, for some time it is was open whether the regularity of the hairpin completion of a regular language is is decidable. In 2009 this decidability problem has been solved positively by providing a polynomial time algorithm. In this paper we improve the complexity bound by showing that the decision problem is actually NL-complete. This complexity bound holds for both, the one-sided and the two-sided hairpin completions

DNA cruciform arms nucleate through a correlated but non-synchronous cooperative mechanism

Inverted repeat (IR) sequences in DNA can form non-canonical cruciform structures to relieve torsional stress. We use Monte Carlo simulations of a recently developed coarse-grained model of DNA to demonstrate that the nucleation of a cruciform can proceed through a cooperative mechanism. Firstly, a twist-induced denaturation bubble must diffuse so that its midpoint is near the centre of symmetry of the IR sequence. Secondly, bubble fluctuations must be large enough to allow one of the arms to form a small number of hairpin bonds. Once the first arm is partially formed, the second arm can rapidly grow to a similar size. Because bubbles can twist back on themselves, they need considerably fewer bases to resolve torsional stress than the final cruciform state does. The initially stabilised cruciform therefore continues to grow, which typically proceeds synchronously, reminiscent of the S-type mechanism of cruciform formation. By using umbrella sampling techniques we calculate, for different temperatures and superhelical densities, the free energy as a function of the number of bonds in each cruciform along the correlated but non-synchronous nucleation pathways we observed in direct simulations.Comment: 12 pages main paper + 11 pages supplementary dat

Statistical properties of thermodynamically predicted RNA secondary structures in viral genomes

By performing a comprehensive study on 1832 segments of 1212 complete genomes of viruses, we show that in viral genomes the hairpin structures of thermodynamically predicted RNA secondary structures are more abundant than expected under a simple random null hypothesis. The detected hairpin structures of RNA secondary structures are present both in coding and in noncoding regions for the four groups of viruses categorized as dsDNA, dsRNA, ssDNA and ssRNA. For all groups hairpin structures of RNA secondary structures are detected more frequently than expected for a random null hypothesis in noncoding rather than in coding regions. However, potential RNA secondary structures are also present in coding regions of dsDNA group. In fact we detect evolutionary conserved RNA secondary structures in conserved coding and noncoding regions of a large set of complete genomes of dsDNA herpesviruses.Comment: 9 pages, 2 figure

Crowding-induced hybridization of single DNA hairpins

It is clear that a crowded environment influences the structure, dynamics, and interactions of biological molecules, but the complexity of this phenomenon demands the development of new experimental and theoretical approaches. Here we use two complementary single-molecule FRET techniques to show that the kinetics of DNA base pairing and unpairing, which are fundamental to both the biological role of DNA and its technological applications, are strongly modulated by a crowded environment. We directly observed single DNA hairpins, which are excellent model systems for studying hybridization, either freely diffusing in solution or immobilized on a surface under crowding conditions. The hairpins followed two-state folding dynamics with a closing rate increasing by 4-fold and the opening rate decreasing 2-fold, for only modest concentrations of crowder [10% (w/w) polyethylene glycol (PEG)]. These experiments serve both to unambiguously highlight the impact of a crowded environment on a fundamental biological process, DNA base pairing, and to illustrate the benefits of single-molecule approaches to probing the structure and dynamics of complex biomolecular systems

Autism-associated SNPs in the clock genes _npas2_, _per1_ and the homeobox gene _en2_ alter DNA sequences that show characteristics of microRNA genes.

Intronic single nucleotide polymorphisms (SNPs) in the clock genes _npas2_ and _per1_ and the homeobox gene _en2_ are reported to be associated with autism. This bioinformatics analysis of the intronic regions which contain the autism-associated SNPs rs1861972 and rs1861973 in _en2_, rs1811399 in _npas2_, and rs885747 in _per1_, shows that these regions encode RNA transcripts with predicted structural characteristics of microRNAs. These microRNA-like structures are disrupted _in silico_ by the presence of the autism enriched alleles of rs1861972, rs1861973, rs1811399 and rs885747 specifically, as compared with the minor alleles of these SNPs. The predicted gene targets of these microRNA-like structures include genes reported to be implicated in autism (_gabrb3_, _shank3_) and genes causative of diseases co-morbid with autism (_mecp2_ and _rai1_). The inheritance of the AC haplotype of rs1861972 - rs1861973 in _en2_, the C allele of rs1811399 in _npas2_, and the C allele of rs1234747 in _per1_ may contribute to the causes of autism by affecting microRNA genes that are co-expressed along with the homeobox gene _en2_ and the circadian genes _npas2_ and _per1_