Mutations as Levy flights

Data from a long time evolution experiment with Escherichia Coli and from a large study on copy number variations in subjects with european ancestry are analyzed in order to argue that mutations can be described as Levy flights in the mutation space. These Levy flights have at least two components: random single-base substitutions and large DNA rearrangements. From the data, we get estimations for the time rates of both events and the size distribution function of large rearrangements

Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process

Breakage-Fusion-Bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then 'unfolds' into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. The process has parallels with paper folding sequences that arise when a piece of paper is folded several times and then unfolded. Here we adapt such methods to study the breakage-fusion-bridge structures in detail. We firstly consider discrete representations of this space with 2-d trees to demonstrate that there are 2^(n(n-1)/2) qualitatively distinct evolutions involving n breakage-fusion-bridge cycles. Secondly we consider the stochastic nature of the fold positions, to determine evolution likelihoods, and also describe how amplicons become localised. Finally we highlight these methods by inferring the evolution of breakage-fusion-bridge cycles with data from primary tissue cancer samples

A Computational Method for the Rate Estimation of Evolutionary Transpositions

Genome rearrangements are evolutionary events that shuffle genomic architectures. Most frequent genome rearrangements are reversals, translocations, fusions, and fissions. While there are some more complex genome rearrangements such as transpositions, they are rarely observed and believed to constitute only a small fraction of genome rearrangements happening in the course of evolution. The analysis of transpositions is further obfuscated by intractability of the underlying computational problems. We propose a computational method for estimating the rate of transpositions in evolutionary scenarios between genomes. We applied our method to a set of mammalian genomes and estimated the transpositions rate in mammalian evolution to be around 0.26.Comment: Proceedings of the 3rd International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO), 2015. (to appear

A genome-wide survey of segmental duplications that mediate common human genetic variation of chromosomal architecture.

Recent studies have identified a small number of genomic rearrangements that occur frequently in the general population. Bioinformatics tools are now available for systematic genome-wide surveys of higher-order structures predisposing to such common variations in genomic architecture. Segmental duplications (SDs) constitute up to 5 per cent of the genome and play an important role in generating additional rearrangements and in disease aetiology. We conducted a genome-wide database search for a form of SD, palindromic segmental duplications (PSDs), which consist of paired, inverted duplications, and which predispose to inversions, duplications and deletions. The survey was complemented by a search for SDs in tandem orientation (TSDs) that can mediate duplications and deletions but not inversions. We found more than 230 distinct loci with higher-order genomic structure that can mediate genomic variation, of these about 180 contained a PSD. A number of these sites were previously identified as harbouring common inversions or as being associated with specific genomic diseases characterised by duplication, deletions or inversions. Most of the regions, however, were previously unidentified; their characterisation should identify further common rearrangements and may indicate localisations for additional genomic disorders. The widespread distribution of complex chromosomal architecture suggests a potentially high degree of plasticity of the human genome and could uncover another level of genetic variation within human populations

Global divergence of microbial genome sequences mediated by propagating fronts

We model the competition between recombination and point mutation in microbial genomes, and present evidence for two distinct phases, one uniform, the other genetically diverse. Depending on the specifics of homologous recombination, we find that global sequence divergence can be mediated by fronts propagating along the genome, whose characteristic signature on genome structure is elucidated, and apparently observed in closely-related {\it Bacillus} strains. Front propagation provides an emergent, generic mechanism for microbial "speciation", and suggests a classification of microorganisms on the basis of their propensity to support propagating fronts

Quantifying evolutionary constraints on B cell affinity maturation

The antibody repertoire of each individual is continuously updated by the evolutionary process of B cell receptor mutation and selection. It has recently become possible to gain detailed information concerning this process through high-throughput sequencing. Here, we develop modern statistical molecular evolution methods for the analysis of B cell sequence data, and then apply them to a very deep short-read data set of B cell receptors. We find that the substitution process is conserved across individuals but varies significantly across gene segments. We investigate selection on B cell receptors using a novel method that side-steps the difficulties encountered by previous work in differentiating between selection and motif-driven mutation; this is done through stochastic mapping and empirical Bayes estimators that compare the evolution of in-frame and out-of-frame rearrangements. We use this new method to derive a per-residue map of selection, which provides a more nuanced view of the constraints on framework and variable regions.Comment: Previously entitled "Substitution and site-specific selection driving B cell affinity maturation is consistent across individuals