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Genome rearrangement events are widely used to estimate a minimum-size sequence of mutations capable of transforming a genome into another. The length of this sequence is called distance, and determining it is the main goal in genome rearrangement distance problems. Problems in the genome rearrangement field differ regarding the set of rearrangement events allowed and the genome representation. In this work, we consider the scenario where the genomes share the same set of genes, gene orientation is known or unknown, and intergenic regions (structures between a pair of genes and at the extremities of the genome) are taken into account. We use two models, the first model allows only conservative events (reversals and moves), and the second model includes non-conservative events (insertions and deletions) in the intergenic regions. We show that both models result in NP-hard problems no matter if gene orientation is known or unknown. When the information regarding the orientation of genes is available, we present for both models an approximation algorithm with a factor of 2. For the scenario where this information is unavailable, we propose a 4-approximation algorithm for both models.

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BACKGROUND: SORTING BY TRANSPOSITIONS (SBT) is a classical problem in genome rearrangements. In 2012, SBT was proven to be [Formula: see text]-hard and the best approximation algorithm with a 1.375 ratio was proposed in 2006 by Elias and Hartman (EH algorithm). Their algorithm employs simplification, a technique used to transform an input permutation [Formula: see text] into a simple permutation [Formula: see text], presumably easier to handle with. The permutation [Formula: see text] is obtained by inserting new symbols into [Formula: see text] in a way that the lower bound of the transposition distance of [Formula: see text] is kept on [Formula: see text]. The simplification is guaranteed to keep the lower bound, not the transposition distance. A sequence of operations sorting [Formula: see text] can be mimicked to sort [Formula: see text]. RESULTS AND CONCLUSIONS: First, using an algebraic approach, we propose a new upper bound for the transposition distance, which holds for all [Formula: see text]. Next, motivated by a problem identified in the EH algorithm, which causes it, in scenarios involving how the input permutation is simplified, to require one extra transposition above the 1.375-approximation ratio, we propose a new approximation algorithm to solve SBT ensuring the 1.375-approximation ratio for all [Formula: see text]. We implemented our algorithm and EH's. Regarding the implementation of the EH algorithm, two other issues were identified and needed to be fixed. We tested both algorithms against all permutations of size n, [Formula: see text]. The results show that the EH algorithm exceeds the approximation ratio of 1.375 for permutations with a size greater than 7. The percentage of computed distances that are equal to transposition distance, computed by the implemented algorithms are also compared with others available in the literature. Finally, we investigate the performance of both implementations on longer permutations of maximum length 500. From the experiments, we conclude that maximum and the average distances computed by our algorithm are a little better than the ones computed by the EH algorithm and the running times of both algorithms are similar, despite the time complexity of our algorithm being higher.

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BACKGROUND: In the comparative genomics field, one of the goals is to estimate a sequence of genetic changes capable of transforming a genome into another. Genome rearrangement events are mutations that can alter the genetic content or the arrangement of elements from the genome. Reversal and transposition are two of the most studied genome rearrangement events. A reversal inverts a segment of a genome while a transposition swaps two consecutive segments. Initial studies in the area considered only the order of the genes. Recent works have incorporated other genetic information in the model. In particular, the information regarding the size of intergenic regions, which are structures between each pair of genes and in the extremities of a linear genome. RESULTS AND CONCLUSIONS: In this work, we investigate the SORTING BY INTERGENIC REVERSALS AND TRANSPOSITIONS problem on genomes sharing the same set of genes, considering the cases where the orientation of genes is known and unknown. Besides, we explored a variant of the problem, which generalizes the transposition event. As a result, we present an approximation algorithm that guarantees an approximation factor of 4 for both cases considering the reversal and transposition (classic definition) events, an improvement from the 4.5-approximation previously known for the scenario where the orientation of the genes is unknown. We also present a 3-approximation algorithm by incorporating the generalized transposition event, and we propose a greedy strategy to improve the performance of the algorithms. We performed practical tests adopting simulated data which indicated that the algorithms, in both cases, tend to perform better when compared with the best-known algorithms for the problem. Lastly, we conducted experiments using real genomes to demonstrate the applicability of the algorithms.

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One of the main problems in Computational Biology is to find the evolutionary distance among species. In most approaches, such distance only involves rearrangements, which are mutations that alter large pieces of the species' genome. When we represent genomes as permutations, the problem of transforming one genome into another is equivalent to the problem of Sorting Permutations by Rearrangement Operations. The traditional approach is to consider that any rearrangement has the same probability to happen, and so, the goal is to find a minimum sequence of operations which sorts the permutation. However, studies have shown that some rearrangements are more likely to happen than others, and so a weighted approach is more realistic. In a weighted approach, the goal is to find a sequence which sorts the permutations, such that the cost of that sequence is minimum. This work introduces a new type of cost function, which is related to the amount of fragmentation caused by a rearrangement. We present some results about the lower and upper bounds for the fragmentation-weighted problems and the relation between the unweighted and the fragmentation-weighted approach. Our main results are 2-approximation algorithms for five versions of this problem involving reversals and transpositions. We also give bounds for the diameters concerning these problems and provide an improved approximation factor for simple permutations considering transpositions.

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During the evolutionary process, genomes are affected by various genome rearrangements, that is, events that modify large stretches of the genetic material. In the literature, a large number of models have been proposed to estimate the number of events that occurred during evolution; most of them represent a genome as an ordered sequence of genes, and, in particular, disregard the genetic material between consecutive genes. However, recent studies showed that taking into account the genetic material between consecutive genes can enhance evolutionary distance estimations. Reversal and transposition are genome rearrangements that have been widely studied in the literature. A reversal inverts a (contiguous) segment of the genome, while a transposition swaps the positions of two consecutive segments. Genomes also undergo nonconservative events (events that alter the amount of genetic material) such as insertions and deletions, in which genetic material from intergenic regions of the genome is inserted or deleted, respectively. In this article, we study a genome rearrangement model that considers both gene order and sizes of intergenic regions. We investigate the reversal distance, and also the reversal and transposition distance between two genomes in two scenarios: with and without nonconservative events. We show that these problems are NP-hard and we present constant ratio approximation algorithms for all of them. More precisely, we provide a 4-approximation algorithm for the reversal distance, both in the conservative and nonconservative versions. For the reversal and transposition distance, we provide a 4.5-approximation algorithm, both in the conservative and nonconservative versions. We also perform experimental tests to verify the behavior of our algorithms, as well as to compare the practical and theoretical results. We finally extend our study to scenarios in which events have different costs, and we present constant ratio approximation algorithms for each scenario.

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BACKGROUND: The evolutionary distance between two genomes can be estimated by computing a minimum length sequence of operations, called genome rearrangements, that transform one genome into another. Usually, a genome is modeled as an ordered sequence of genes, and most of the studies in the genome rearrangement literature consist in shaping biological scenarios into mathematical models. For instance, allowing different genome rearrangements operations at the same time, adding constraints to these rearrangements (e.g., each rearrangement can affect at most a given number of genes), considering that a rearrangement implies a cost depending on its length rather than a unit cost, etc. Most of the works, however, have overlooked some important features inside genomes, such as the presence of sequences of nucleotides between genes, called intergenic regions. RESULTS AND CONCLUSIONS: In this work, we investigate the problem of computing the distance between two genomes, taking into account both gene order and intergenic sizes. The genome rearrangement operations we consider here are constrained types of reversals and transpositions, called super short reversals (SSRs) and super short transpositions (SSTs), which affect up to two (consecutive) genes. We denote by super short operations (SSOs) any SSR or SST. We show 3-approximation algorithms when the orientation of the genes is not considered when we allow SSRs, SSTs, or SSOs, and 5-approximation algorithms when considering the orientation for either SSRs or SSOs. We also show that these algorithms improve their approximation factors when the input permutation has a higher number of inversions, where the approximation factor decreases from 3 to either 2 or 1.5, and from 5 to either 3 or 2.

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Genome rearrangements are global mutations that change large stretches of DNA sequence throughout genomes. They are rare but accumulate during the evolutionary process leading to organisms with similar genetic material in different places and orientations within the genome. Sorting by Genome Rearrangements problems seek for minimum-length sequences of rearrangements that transform one genome into the other. These problems accept alternative versions that assign weights for each event, and the goal is to find a minimum-weight sequence. We study the Sorting by Weighted Reversals and Transpositions problem on signed permutations. In this study, we use weight 2 for reversals and 3 for transpositions and consider theoretical and practical aspects in our analysis. We present two algorithms with approximation factors of 5/3 and 3/2. We also developed a generic approximation algorithm to deal with different weights for reversals and transpositions, and we show the approximation factor reached in each scenario.

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Some interesting combinatorial problems have been motivated by genome rearrangements, which are mutations that affect large portions of a genome. When we represent genomes as permutations, the goal is to transform a given permutation into the identity permutation with the minimum number of rearrangements. When they affect segments from the beginning (respectively end) of the permutation, they are called prefix (respectively suffix) rearrangements. This paper presents results for rearrangement problems that involve prefix and suffix versions of reversals and transpositions considering unsigned and signed permutations. We give 2-approximation and ([Formula: see text])-approximation algorithms for these problems, where [Formula: see text] is a constant divided by the number of breakpoints (pairs of consecutive elements that should not be consecutive in the identity permutation) in the input permutation. We also give bounds for the diameters concerning these problems and provide ways of improving the practical results of our algorithms.

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Sorting by Transpositions is an NP-hard problem for which several polynomial-time approximation algorithms have been developed. Hartman and Shamir (2006) developed a 1.5-approximation [Formula: see text] algorithm, whose running time was improved to O(nlogn) by Feng and Zhu (2007) with a data structure they defined, the permutation tree. Elias and Hartman (2006) developed a 1.375-approximation O(n(2)) algorithm, and Firoz et al. (2011) claimed an improvement to the running time, from O(n(2)) to O(nlogn), by using the permutation tree. We provide counter-examples to the correctness of Firoz et al.'s strategy, showing that it is not possible to reach a component by sufficient extensions using the method proposed by them. In addition, we propose a 1.375-approximation algorithm, modifying Elias and Hartman's approach with the use of permutation trees and achieving O(nlogn) time.

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