A model for codon position bias in RNA editing

RNA editing can be crucial for the expression of genetic information via inserting, deleting, or substituting a few nucleotides at specific positions in an RNA sequence. Within coding regions in an RNA sequence, editing usually occurs with a certain bias in choosing the positions of the editing sites. In the mitochondrial genes of {\it Physarum polycephalum}, many more editing events have been observed at the third codon position than at the first and second, while in some plant mitochondria the second codon position dominates. Here we propose an evolutionary model that explains this bias as the basis of selection at the protein level. The model predicts a distribution of the three positions rather close to the experimental observation in {\it Physarum}. This suggests that the codon position bias in {\it Physarum} is mainly a consequence of selection at the protein level.Comment: 4 pages, 1 figure, submitted to Phys. Rev. Let

Modeling DNA unzipping in the presence of bound proteins

Unzipping force analysis of protein association is a technique to investigate protein-DNA interactions by mechanically unzipping DNA. We computationally investigate the limits of this technique under quasistatic conditions. We find the minimum binding energy of a protein for which the protein can be detected using this technique and the minimum distance between the binding sites of two proteins of varying binding energies that can be resolved unambiguously with this technique

Melting of Branched RNA Molecules

Stability of the branching structure of an RNA molecule is an important condition for its function. In this letter we show that the melting thermodynamics of RNA molecules is very sensitive to their branching geometry for the case of a molecule whose groundstate has the branching geometry of a Cayley Tree and whose pairing interactions are described by the Go model. Whereas RNA molecules with a linear geometry melt via a conventional continuous phase transition with classical exponents, molecules with a Cayley Tree geometry are found to have a free energy that seems smooth, at least within our precision. Yet, we show analytically that this free energy in fact has a mathematical singularity at the stability limit of the ordered structure. The correlation length appears to diverge on the high-temperature side of this singularity.Comment: 4 pages, 3 figure

Numerical Method for Accessing the Universal Scaling Function for a Multi-Particle Discrete Time Asymmetric Exclusion Process

In the universality class of the one dimensional Kardar-Parisi-Zhang surface growth, Derrida and Lebowitz conjectured the universality of not only the scaling exponents, but of an entire scaling function. Since Derrida and Lebowitz's original publication [PRL 80 209 (1998)] this universality has been verified for a variety of continuous time, periodic boundary systems in the KPZ universality class. Here, we present a numerical method for directly examining the entire particle flux of the asymmetric exclusion process (ASEP), thus providing an alternative to more difficult cumulant ratios studies. Using this method, we find that the Derrida-Lebowitz scaling function (DLSF) properly characterizes the large system size limit (N-->infty) of a single particle discrete time system, even in the case of very small system sizes (N <= 22). This fact allows us to not only verify that the DLSF properly characterizes multiple particle discrete-time asymmetric exclusion processes, but also provides a way to numerically solve for quantities of interest, such as the particle hopping flux. This method can thus serve to further increase the ease and accessibility of studies involving even more challenging dynamics, such as the open boundary ASEP

Coupled dynamics of RNA folding and nanopore translocation

The translocation of structured RNA or DNA molecules through narrow pores necessitates the opening of all base pairs. Here, we study the interplay between the dynamics of translocation and base-pairing theoretically, using kinetic Monte Carlo simulations and analytical methods. We find that the transient formation of basepairs that do not occur in the ground state can significantly speed up translocation.Comment: 4 pages, 3 figures, to appear in Physical Review Letter

Discovery of new genes and deletion editing in Physarum mitochondria enabled by a novel algorithm for finding edited mRNAs

Gene finding is complicated in organisms that exhibit insertional RNA editing. Here, we demonstrate how our new algorithm Predictor of Insertional Editing (PIE) can be used to locate genes whose mRNAs are subjected to multiple frameshifting events, and extend the algorithm to include probabilistic predictions for sites of nucleotide insertion; this feature is particularly useful when designing primers for sequencing edited RNAs. Applying this algorithm, we successfully identified the nad2, nad4L, nad6 and atp8 genes within the mitochondrial genome of Physarum polycephalum, which had gone undetected by existing programs. Characterization of their mRNA products led to the unanticipated discovery of nucleotide deletion editing in Physarum. The deletion event, which results in the removal of three adjacent A residues, was confirmed by primer extension sequencing of total RNA. This finding is remarkable in that it comprises the first known instance of nucleotide deletion in this organelle, to be contrasted with nearly 500 sites of single and dinucleotide addition in characterized mitochondrial RNAs. Statistical analysis of this larger pool of editing sites indicates that there are significant biases in the 2 nt immediately upstream of editing sites, including a reduced incidence of nucleotide repeats, in addition to the previously identified purine-U bias