SoRT2: a tool for sorting genomes and reconstructing phylogenetic trees by reversals, generalized transpositions and translocations

SoRT2 is a web server that allows the user to perform genome rearrangement analysis involving reversals, generalized transpositions and translocations (including fusions and fissions), and infer phylogenetic trees of genomes being considered based on their pairwise genome rearrangement distances. It takes as input two or more linear/circular multi-chromosomal gene (or synteny block) orders in FASTA-like format. When the input is two genomes, SoRT2 will quickly calculate their rearrangement distance, as well as a corresponding optimal scenario by highlighting the genes involved in each rearrangement operation. In the case of multiple genomes, SoRT2 will also construct phylogenetic trees of these genomes based on a matrix of their pairwise rearrangement distances using distance-based approaches, such as neighbor-joining (NJ), unweighted pair group method with arithmetic mean (UPGMA) and Fitch–Margoliash (FM) methods. In addition, if the function of computing jackknife support values is selected, SoRT2 will further perform the jackknife analysis to evaluate statistical reliability of the constructed NJ, UPGMA and FM trees. SoRT2 is available online at http://bioalgorithm.life.nctu.edu.tw/SORT2/

Sorting permutations by cut-circularize-linearize-and-paste operations

<p>Abstract</p> <p>Background</p> <p>Genome rearrangements are studied on the basis of genome-wide analysis of gene orders and important in the evolution of species. In the last two decades, a variety of rearrangement operations, such as reversals, transpositions, block-interchanges, translocations, fusions and fissions, have been proposed to evaluate the differences between gene orders in two or more genomes. Usually, the computational studies of genome rearrangements are formulated as problems of sorting permutations by rearrangement operations.</p> <p>Result</p> <p>In this article, we study a sorting problem by cut-circularize-linearize-and-paste (CCLP) operations, which aims to find a minimum number of CCLP operations to sort a signed permutation representing a chromosome. The CCLP is a genome rearrangement operation that cuts a segment out of a chromosome, circularizes the segment into a temporary circle, linearizes the temporary circle as a linear segment, and possibly inverts the linearized segment and pastes it into the remaining chromosome. The CCLP operation can model many well-known rearrangements, such as reversals, transpositions and block-interchanges, and others not reported in the biological literature. In addition, it really occurs in the immune response of higher animals. To distinguish those CCLP operations from the reversal, we call them as non-reversal CCLP operations. In this study, we use permutation groups in algebra to design an <it>O</it>(<it>δn</it>) time algorithm for solving the weighted sorting problem by CCLP operations when the weight ratio between reversals and non-reversal CCLP operations is 1:2, where <it>n</it> is the number of genes in the given chromosome and <it>δ</it> is the number of needed CCLP operations.</p> <p>Conclusion</p> <p>The algorithm we propose in this study is very simple so that it can be easily implemented with 1-dimensional arrays and useful in the studies of phylogenetic tree reconstruction and human immune response to tumors.</p

Sobre modelos de rearranjo de genomas

Orientador: João MeidanisTese (doutorado) - Universidade Estadual de Campinas, Instituto de ComputaçãoResumo: Rearranjo de genomas é o nome dado a eventos onde grandes blocos de DNA trocam de posição durante o processo evolutivo. Com a crescente disponibilidade de sequências completas de DNA, a análise desse tipo de eventos pode ser uma importante ferramenta para o entendimento da genômica evolutiva. Vários modelos matemáticos de rearranjo de genomas foram propostos ao longo dos últimos vinte anos. Nesta tese, desenvolvemos dois novos modelos. O primeiro foi proposto como uma definição alternativa ao conceito de distância de breakpoint. Essa distância é uma das mais simples medidas de rearranjo, mas ainda não há um consenso quanto à sua definição para o caso de genomas multi-cromossomais. Pevzner e Tesler deram uma definição em 2003 e Tannier et al. a definiram de forma diferente em 2008. Nesta tese, nós desenvolvemos uma outra alternativa, chamada de single-cut-or-join (SCJ). Nós mostramos que, no modelo SCJ, além da distância, vários problemas clássicos de rearranjo, como a mediana de rearranjo, genome halving e pequena parcimônia são fáceis, e apresentamos algoritmos polinomiais para eles. O segundo modelo que apresentamos é o formalismo algébrico por adjacências, uma extensão do formalismo algébrico proposto por Meidanis e Dias, que permite a modelagem de cromossomos lineares. Esta era a principal limitação do formalismo original, que só tratava de cromossomos circulares. Apresentamos algoritmos polinomiais para o cálculo da distância algébrica e também para encontrar cenários de rearranjo entre dois genomas. Também mostramos como calcular a distância algébrica através do grafo de adjacências, para facilitar a comparação com outras distâncias de rearranjo. Por fim, mostramos como modelar todas as operações clássicas de rearranjo de genomas utilizando o formalismo algébricoAbstract: Genome rearrangements are events where large blocks of DNA exchange places during evolution. With the growing availability of whole genome data, the analysis of these events can be a very important and promising tool for understanding evolutionary genomics. Several mathematical models of genome rearrangement have been proposed in the last 20 years. In this thesis, we propose two new rearrangement models. The first was introduced as an alternative definition of the breakpoint distance. The breakpoint distance is one of the most straightforward genome comparison measures, but when it comes to defining it precisely for multichromosomal genomes, there is more than one way to go about it. Pevzner and Tesler gave a definition in a 2003 paper, and Tannier et al. defined it differently in 2008. In this thesis we provide yet another alternative, calling it single-cut-or-join (SCJ). We show that several genome rearrangement problems, such as genome median, genome halving and small parsimony, become easy for SCJ, and provide polynomial time algorithms for them. The second model we introduce is the Adjacency Algebraic Theory, an extension of the Algebraic Formalism proposed by Meidanis and Dias that allows the modeling of linear chromosomes, the main limitation of the original formalism, which could deal with circular chromosomes only. We believe that the algebraic formalism is an interesting alternative for solving rearrangement problems, with a different perspective that could complement the more commonly used combinatorial graph-theoretic approach. We present polynomial time algorithms to compute the algebraic distance and find rearrangement scenarios between two genomes. We show how to compute the rearrangement distance from the adjacency graph, for an easier comparison with other rearrangement distances. Finally, we show how all classic rearrangement operations can be modeled using the algebraic theoryDoutoradoCiência da ComputaçãoDoutor em Ciência da Computaçã

Are There Rearrangement Hotspots in the Human Genome?

In a landmark paper, Nadeau and Taylor [18] formulated the random breakage model (RBM) of chromosome evolution that postulates that there are no rearrangement hotspots in the human genome. In the next two decades, numerous studies with progressively increasing levels of resolution made RBM the de facto theory of chromosome evolution. Despite the fact that RBM had prophetic prediction power, it was recently refuted by Pevzner and Tesler [4], who introduced the fragile breakage model (FBM), postulating that the human genome is a mosaic of solid regions (with low propensity for rearrangements) and fragile regions (rearrangement hotspots). However, the rebuttal of RBM caused a controversy and led to a split among researchers studying genome evolution. In particular, it remains unclear whether some complex rearrangements (e.g., transpositions) can create an appearance of rearrangement hotspots. We contribute to the ongoing debate by analyzing multi-break rearrangements that break a genome into multiple fragments and further glue them together in a new order. In particular, we demonstrate that (1) even if transpositions were a dominant force in mammalian evolution, the arguments in favor of FBM still stand, and (2) the ‘‘gene deletion’’ argument against FBM is flawed

A path-deformation framework for determining weighted genome rearrangement distance

Measuring the distance between two bacterial genomes under the inversion process is usually done by assuming all inversions to occur with equal probability. Recently, an approach to calculating inversion distance using group theory was introduced, and is effective for the model in which only very short inversions occur. In this paper, we show how to use the group-theoretic framework to establish minimal distance for any weighting on the set of inversions, generalizing previous approaches. To do this we use the theory of rewriting systems for groups, and exploit the Knuth--Bendix algorithm, the first time this theory has been introduced into genome rearrangement problems. The central idea of the approach is to use existing group theoretic methods to find an initial path between two genomes in genome space (for instance using only short inversions), and then to deform this path to optimality using a confluent system of rewriting rules generated by the Knuth--Bendix algorithm

On the distribution of the number of cycles in the breakpoint graph of a random signed permutation

International audienceWe use the finite Markov chain embedding technique to obtain the distribution of the number of cycles in the breakpoint graph of a random uniform signed permutation. This further gives a very good approximation of the distribution of the reversal distance between two random genomes

A High-Resolution Map of Synteny Disruptions in Gibbon and Human Genomes

Gibbons are part of the same superfamily (Hominoidea) as humans and great apes, but their karyotype has diverged faster from the common hominoid ancestor. At least 24 major chromosome rearrangements are required to convert the presumed ancestral karyotype of gibbons into that of the hominoid ancestor. Up to 28 additional rearrangements distinguish the various living species from the common gibbon ancestor. Using the northern white-cheeked gibbon (2n = 52) (Nomascus leucogenys leucogenys) as a model, we created a high-resolution map of the homologous regions between the gibbon and human. The positions of 100 synteny breakpoints relative to the assembled human genome were determined at a resolution of about 200 kb. Interestingly, 46% of the gibbon–human synteny breakpoints occur in regions that correspond to segmental duplications in the human lineage, indicating a common source of plasticity leading to a different outcome in the two species. Additionally, the full sequences of 11 gibbon BACs spanning evolutionary breakpoints reveal either segmental duplications or interspersed repeats at the exact breakpoint locations. No specific sequence element appears to be common among independent rearrangements. We speculate that the extraordinarily high level of rearrangements seen in gibbons may be due to factors that increase the incidence of chromosome breakage or fixation of the derivative chromosomes in a homozygous state