Comparing RNA structures using a full set of biologically relevant edit operations is intractable

7 pagesArc-annotated sequences are useful for representing structural information of RNAs and have been extensively used for comparing RNA structures in both terms of sequence and structural similarities. Among the many paradigms referring to arc-annotated sequences and RNA structures comparison (see \cite{IGMA_BliDenDul08} for more details), the most important one is the general edit distance. The problem of computing an edit distance between two non-crossing arc-annotated sequences was introduced in \cite{Evans99}. The introduced model uses edit operations that involve either single letters or pairs of letters (never considered separately) and is solvable in polynomial-time \cite{ZhangShasha:1989}. To account for other possible RNA structural evolutionary events, new edit operations, allowing to consider either silmutaneously or separately letters of a pair were introduced in \cite{jiangli}; unfortunately at the cost of computational tractability. It has been proved that comparing two RNA secondary structures using a full set of biologically relevant edit operations is {\sf\bf NP}-complete. Nevertheless, in \cite{DBLP:conf/spire/GuignonCH05}, the authors have used a strong combinatorial restriction in order to compare two RNA stem-loops with a full set of biologically relevant edit operations; which have allowed them to design a polynomial-time and space algorithm for comparing general secondary RNA structures. In this paper we will prove theoretically that comparing two RNA structures using a full set of biologically relevant edit operations cannot be done without strong combinatorial restrictions

Local Similarity Between Quotiented Ordered Trees

International audienceIn this paper we propose a dynamic programming algorithm to evaluate local similarity between ordered quotiented trees using a constrained edit scoring scheme. A quotiented tree is a tree defined with an additional equivalent relation on vertices and such that the quotient graph is also a tree. The core of the method relies on two adaptations of an algorithm proposed by Zhang et al. [K. Zhang, D. Shasha, Simple fast algorithms for the editing distance between trees and related problems (1989) 1245-1262] for comparing ordered rooted trees. After some preliminary definitions and the description of this tree edit algorithm, we propose extensions to globally and locally compare two quotiented trees. This last method allows to find the region in each tree with the highest similarity. Algorithms are currently being used in genomic analysis to evaluate variability between RNA secondary structures

Louse (Insecta : Phthiraptera) mitochondrial 12S rRNA secondary structure is highly variable

Lice are ectoparasitic insects hosted by birds and mammals. Mitochondrial 12S rRNA sequences obtained from lice show considerable length variation and are very difficult to align. We show that the louse 12S rRNA domain III secondary structure displays considerable variation compared to other insects, in both the shape and number of stems and loops. Phylogenetic trees constructed from tree edit distances between louse 12S rRNA structures do not closely resemble trees constructed from sequence data, suggesting that at least some of this structural variation has arisen independently in different louse lineages. Taken together with previous work on mitochondrial gene order and elevated rates of substitution in louse mitochondrial sequences, the structural variation in louse 12S rRNA confirms the highly distinctive nature of molecular evolution in these insects

Efficient chaining of seeds in ordered trees

We consider here the problem of chaining seeds in ordered trees. Seeds are mappings between two trees Q and T and a chain is a subset of non overlapping seeds that is consistent with respect to postfix order and ancestrality. This problem is a natural extension of a similar problem for sequences, and has applications in computational biology, such as mining a database of RNA secondary structures. For the chaining problem with a set of m constant size seeds, we describe an algorithm with complexity O(m2 log(m)) in time and O(m2) in space

Reconstructing phylogeny from RNA secondary structure via simulated evolution

DNA sequences of genes encoding functional RNA molecules (e.g., ribosomal RNAs) are commonly used in phylogenetics (i.e. to infer evolutionary history). Trees derived from ribosomal RNA (rRNA) sequences, however, are inconsistent with other molecular data in investigations of deep branches in the tree of life. Since much of te functional constraints on the gene products (i.e. RNA molecules) relate to three-dimensional structure, rather than their actual sequences, accumulated mutations in the gene sequences may obscure phylogenetic signal over very large evolutionary time-scales. Variation in structure, however, may be suitable for phylogenetic inference even under extreme sequence divergence. To evaluate qualitatively the manner in which structural evolution relates to sequence change, we simulated the evolution of RNA sequences under various constraints on structural change

Actions of Agonists, Fipronil and Ivermectin on the Predominant In Vivo Splice and Edit Variant (RDLbd, I/V) of the Drosophila GABA Receptor Expressed in Xenopus laevis Oocytes

Ionotropic GABA receptors are the targets for several classes of insecticides. One of the most widely-studied insect GABA receptors is RDL (resistance to dieldrin), originally isolated from Drosophila melanogaster. RDL undergoes alternative splicing and RNA editing, which influence the potency of GABA. Most work has focussed on minority isoforms. Here, we report the first characterisation of the predominant native splice variant and RNA edit, combining functional characterisation with molecular modelling of the agonist-binding region. The relative order of agonist potency is GABA> muscimol> TACA> β-alanine. The I/V edit does not alter the potency of GABA compared to RDLbd. Docking calculations suggest that these agonists bind and activate RDLbdI/V through a similar binding mode. TACA and β-alanine are predicted to bind with lower affinity than GABA, potentially explaining their lower potency, whereas the lower potency of muscimol and isoguvacine cannot be explained structurally from the docking calculations. The A301S (resistance to dieldrin) mutation reduced the potency of antagonists picrotoxin, fipronil and pyrafluprole but the I/V edit had no measurable effect. Ivermectin suppressed responses to GABA of RDLbdI/V, RDLbd and RDLbdI/VA301S. The dieldrin resistant variant also showed reduced sensitivity to Ivermectin. This study of a highly abundant insect GABA receptor isoform will help the design of new insecticides