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

Limited Lifespan of Fragile Regions in Mammalian Evolution

An important question in genome evolution is whether there exist fragile regions (rearrangement hotspots) where chromosomal rearrangements are happening over and over again. Although nearly all recent studies supported the existence of fragile regions in mammalian genomes, the most comprehensive phylogenomic study of mammals (Ma et al. (2006) Genome Research 16, 1557-1565) raised some doubts about their existence. We demonstrate that fragile regions are subject to a "birth and death" process, implying that fragility has limited evolutionary lifespan. This finding implies that fragile regions migrate to different locations in different mammals, explaining why there exist only a few chromosomal breakpoints shared between different lineages. The birth and death of fragile regions phenomenon reinforces the hypothesis that rearrangements are promoted by matching segmental duplications and suggests putative locations of the currently active fragile regions in the human genome

On the DCJ Median Problem

As many whole genomes are sequenced, comparative genomics is moving from pairwise comparisons to multiway comparisons framed within a phylogenetic tree. A central problem in this process is the inference of data for internal nodes of the tree from data given at the leaves. When phrased as an optimization problem, this problem reduces to computing a median of three genomes under the operations (evolutionary changes) of interest. We focus on the universal rearrangement operation known as double-cut-and join (DCJ) and present three contributions to the DCJ median problem. First, we describe a new strategy to find so-called adequate subgraphs in the multiple breakpoint graph, using a seed genome. We show how to compute adequate subgraphs w.r.t. this seed genome using a network flow formulation. Second, we prove that the upper bound of the median distance computed from the triangle inequality is tight. Finally, we study the question of whether the median distance can reach its lower and upper bounds. We derive a necessary and sufficient condition for the median distance to reach its lower bound and a necessary condition for it to reach its upper bound and design algorithms to test for these conditions

SCJ: A Variant of Breakpoint Distance for Which Sorting, Genome Median and Genome Halving Problems Are Easy

Feijão P, Meidanis J. SCJ: A Variant of Breakpoint Distance for Which Sorting, Genome Median and Genome Halving Problems Are Easy. In: Salzberg SL, Warnow T, eds. Algorithms in Bioinformatics. Lecture Notes in Computer Science. Vol 5724. Berlin, Heidelberg: Springer Berlin Heidelberg; 2009: 85-96

Fast and accurate phylogenetic reconstruction from high-resolution whole-genome data and a novel robustness estimator

The rapid accumulation of whole-genome data has renewed interest in the study of genomic rearrangements. Comparative genomics, evolutionary biology, and cancer research all require models and algorithms to elucidate the mechanisms, history, and consequences of these rearrangements. However, even simple models lead to NP-hard problems, particularly in the area of phylogenetic analysis. Current approaches are limited to small collections of genomes and low-resolution data (typically a few hundred syntenic blocks). Moreover, whereas phylogenetic analyses from sequence data are deemed incomplete unless bootstrapping scores (a measure of confidence) are given for each tree edge, no equivalent to bootstrapping exists for rearrangement-based phylogenetic analysis. We describe a fast and accurate algorithm for rearrangement analysis that scales up, in both time and accuracy, to modern high-resolution genomic data. We also describe a novel approach to estimate the robustness of results-an equivalent to the bootstrapping analysis used in sequence-based phylogenetic reconstruction. We present the results of extensive testing on both simulated and real data showing that our algorithm returns very accurate results, while scaling linearly with the size of the genomes and cubically with their number. We also present extensive experimental results showing that our approach to robustness testing provides excellent estimates of confidence, which, moreover, can be tuned to trade off thresholds between false positives and false negatives. Together, these two novel approaches enable us to attack heretofore intractable problems, such as phylogenetic inference for high-resolution vertebrate genomes, as we demonstrate on a set of six vertebrate genomes with 8,380 syntenic blocks. A copy of the software is available on demand