Hannenhalli and Pevzner gave the first polynomial-time algorithm for computing the inversion distance between two signed permutations, as part of the larger task of determining the shortest sequence of inversions needed to transform one permutation into the other. Their algorithm (restricted to distance calculation) proceeds in two stages: in the first stage, the overlap graph induced by the permutation is decomposed into connected components; then, in the second stage, certain graph structures (hurdles and others) are identified. Berman and Hannenhalli avoided the explicit computation of the overlap graph and gave an O(n alpha(n)) algorithm, based on a Union-Find structure, to find its connected components, where a is the inverse Ackerman function. Since for all practical purposes alpha(n) is a constant no larger than four, this algorithm has been the fastest practical algorithm to date. In this paper, we present a new linear-time algorithm for computing the connected components, which is more efficient than that of Berman and Hannenhalli in both theory and practice. Our algorithm uses only a stack and is very easy to implement. We give the results of computational experiments over a large range of permutation pairs produced through simulated evolution; our experiments show a speed-up by a factor of 2 to 5 in the computation of the connected components and by a factor of 1.3 to 2 in the overall distance computation.

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Motivation: Phylogenetic reconstruction from gene-order data has attracted increasing attention from both biologists and computer scientists over the last few years. Methods used in reconstruction include distance-based methods (such as neighbor-joining), parsimony methods using sequence-based encodings, Bayesian approaches, and direct optimization. The latter, pioneered by Sankoff and extended by us with the software suite GRAPPA, is the most accurate approach, but cannot handle more than about 15 genomes of limited size (e.g., organelles). Results: We report here on our successful efforts to scale up direct optimization through a two-step approach: the first step decomposes the dataset into smaller pieces and runs the direct optimization (GRAPPA) on the smaller pieces, while the second step builds a tree from the results obtained on the smaller pieces. We used the sophisticated disk-covering method (DCM) pioneered by Warnow and her group, suitably modified to take into account the computational limitations of GRAPPA. We find that DCM-GRAPPA scales gracefully to at least 1,000 genomes of a few hundred genes each and retains surprisingly high accuracy throughout the range: in our experiments, the topological error rate rarely exceeded a few percent. Thus, reconstruction based on gene-order data can now be accomplished with high accuracy on datasets of significant size. Availability: All of our software is available in source form under GPL at www.compbio.unm.edu Contact:

Phylogenies (that is, tree-of-life relationships) derived from gene order data may prove crucial in answering some fundamental open questions in biomolecular evolution. Real-world interest is strong in determining these relationships. For example, pharmaceutical companies may use phylogeny reconstruction in drug discovery for finding plants with similar gene production. Health organizations study the evolution and spread of viruses such as HIV to gain understanding of future outbreaks. And governments are interested in aiding the production of foodstuffs like rice, wheat, and corn, by understanding the genetic code. Yet very few techniques are available for such phylogenetic reconstructions. Appropriate tools for analyzing such data may help resolve some difficult phylogenetic reconstruction problems; indeed, this new source of data has been embraced by many biologists in their phylogenetic work. With the rapid accumulation of whole genome sequences for a wide diversity of taxa, phylogenetic reconstruction based on changes in gene order and gene content is showing promise, particularly for resolving deep (i.e., old) branches. However, reconstruction from gene-order data is even more computationally intensive than reconstruction from sequence data, particularly in groups with large numbers of genes and highly rearranged genomes. We have developed a software suite, GRAPPA, that extends the breakpoint analysis (BPAnalysis) method of Sankoff and Blanchette while running much faster: in a recent analysis of a collection of chloroplast data for species of Campanulaceae on a 512-processor Linux supercluster with Myrinet, we achieved a one-million-fold speedup over BPAnalysis. GRAPPA currently can use either breakpoint or inversion distance (computed exactly) for its computati...

Abstract. We derive a branch-and-bound algorithm to find an optimal inversion median of three signed permutations. The algorithm prunes to manageable size an extremely large search tree using simple geometric properties of the problem and a newly available linear-time routine for inversion distance. Our experiments on simulated data sets indicate that the algorithm finds optimal medians in reasonable time for genomes of medium size when distances are not too large, as commonly occurs in phylogeny reconstruction. In addition, we have compared inversion and breakpoint medians, and found that inversion medians generally score significantly better and tend to be far more unique, which should make them valuable in median-based tree-building algorithms. 1

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Breakpoint phylogenies methods have been shown to be an effective tool for extracting phylogenetic information from gene order data. Currently, the only practical breakpoint phylogeny algorithms for the analysis of large genomes with varied gene content are heuristics with no optimality guarantee. Here we begin to address this lack by deriving lower bounds for the breakpoint median problem and for the more complicated breakpoint phylogeny problem. In both cases we employ Lagrange multipliers and sub-gradient optimization to tighten the bounds. The bounds have been implemented and are available as part of the GOTREE package (http://www.math.mcgill.ca/bryant/gotree). 2003 Elsevier B.V. All rights reserved.

Evolution operates on whole genomes by operations that change the order and strandedness of genes within the genomes. This type of data presents new opportunities for discoveries about deep evolutionary rearrangement events, provided that suciently accurate methods can be developed to reconstruct evolutionary trees in these models [3, 11, 13, 18]. A necessary component of any such method is the ability to accurately estimate the true evolutionary distance between two genomes, which is the number of rearrangement events that took place in the evolutionary history between them. We improve the technique (IEBP) in [21] with a new method, Exact-IEBP, for estimating the true evolutionary distance between two signed genomes. Our simulation study shows Exact-IEBP is a better estimation of true evolutionary distances. Furthermore, Exact-IEBP produces more accurate trees than IEBP when used with the popular distance-based method, neighbor joining [16].