Breakpoint graphs and ancestral genome reconstructions

Alekseyev, Max A.; Pevzner, Pavel A.

doi:10.1101/gr.082784.108

Cited by 121 publications

(132 citation statements)

References 75 publications

(90 reference statements)

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“…Despite some recent improvements in reconstruction algorithms (3,(14)(15)(16), the field has been more or less stagnant for the past decade because of the paucity of new genome assemblies suitable for ancestral reconstructions. In this paper, we introduce a method, called DESCHRAMBLER, which uses SFs constructed from whole-genome comparisons of both high-quality chromosomescale and fragmented assemblies.…”

Section: Significancementioning

confidence: 99%

Reconstruction and evolutionary history of eutherian chromosomes

Kim

Farré

Auvil

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

126

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Whole-genome assemblies of 19 placental mammals and two outgroup species were used to reconstruct the order and orientation of syntenic fragments in chromosomes of the eutherian ancestor and six other descendant ancestors leading to human. For ancestral chromosome reconstructions, we developed an algorithm (DESCHRAMBLER) that probabilistically determines the adjacencies of syntenic fragments using chromosome-scale and fragmented genome assemblies. The reconstructed chromosomes of the eutherian, boreoeutherian, and euarchontoglires ancestor each included >80% of the entire length of the human genome, whereas reconstructed chromosomes of the most recent common ancestor of simians, catarrhini, great apes, and humans and chimpanzees included >90% of human genome sequence. These high-coverage reconstructions permitted reliable identification of chromosomal rearrangements over ∼105 My of eutherian evolution. Orangutan was found to have eight chromosomes that were completely conserved in homologous sequence order and orientation with the eutherian ancestor, the largest number for any species. Ruminant artiodactyls had the highest frequency of intrachromosomal rearrangements, and interchromosomal rearrangements dominated in murid rodents. A total of 162 chromosomal breakpoints in evolution of the eutherian ancestral genome to the human genome were identified; however, the rate of rearrangements was significantly lower (0.80/My) during the first ∼60 My of eutherian evolution, then increased to greater than 2.0/My along the five primate lineages studied. Our results significantly expand knowledge of eutherian genome evolution and will facilitate greater understanding of the role of chromosome rearrangements in adaptation, speciation, and the etiology of inherited and spontaneously occurring diseases. chromosome evolution | ancestral genome reconstruction | genome rearrangements C hromosome rearrangements are a hallmark of genome evolution and essential for understanding the mechanisms of speciation and adaptation (1). Determining chromosome rearrangements over evolutionary time scales has been a difficult problem, primarily because of the lack of high-quality, chromosome-scale genome assemblies that are necessary for reliable reconstruction of ancestral genomes. For closely related species with good map-anchored assemblies, such as human, chimpanzee, and rhesus, it is possible to infer most inversions, translocations, fusions, and fissions that occurred during evolution by simple observational comparisons (2). However, for sequence-based genome-wide comparisons that require resolving large numbers of rearrangements of varying scale, determining ancestral chromosomal states is challenging both methodologically and computationally because of the complexity of genomic events that have led to extant genome organizations, including duplications, deletions, and reuse of evolutionary breakpoint regions (EBRs) flanking regions of homologous synteny (3, 4).A variety of methods have been used for resolving the evolutionary historie...

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Section: Significancementioning

confidence: 99%

Reconstruction and evolutionary history of eutherian chromosomes

Kim

Farré

Auvil

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

126

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“…Given a set of SFs B, the SF graph is an undirected graph G = (V, E), where V = {b h , b t jb ∈ B} is the set of vertices that represents the head b h and tail b t of a SF b, and E is the set of undirected edges. The idea is analogous to the breakpoint graph that was used in genome rearrangement analysis (29,30). The edge between two SFs can be created by connecting either the head or tail vertices of each SF, which represents both the order and orientation of SFs.…”

Section: Methodsmentioning

confidence: 99%

Reference-assisted chromosome assembly

Kim

Larkin

Cai

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

115

136

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One of the most difficult problems in modern genomics is the assembly of full-length chromosomes using next generation sequencing (NGS) data. To address this problem, we developed "reference-assisted chromosome assembly" (RACA), an algorithm to reliably order and orient sequence scaffolds generated by NGS and assemblers into longer chromosomal fragments using comparative genome information and paired-end reads. Evaluation of results using simulated and real genome assemblies indicates that our approach can substantially improve genomes generated by a wide variety of de novo assemblers if a good reference assembly of a closely related species and outgroup genomes are available. We used RACA to reconstruct 60 Tibetan antelope (Pantholops hodgsonii) chromosome fragments from 1,434 SOAPdenovo sequence scaffolds, of which 16 chromosome fragments were homologous to complete cattle chromosomes. Experimental validation by PCR showed that predictions made by RACA are highly accurate. Our results indicate that RACA will significantly facilitate the study of chromosome evolution and genome rearrangements for the large number of genomes being sequenced by NGS that do not have a genetic or physical map.computational genomics | comparative genomics | bioinformatics | chromosome breakpoints | mammals

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“…For example, frameworks such as De Bruijn graphs have aided the assembly of genomes (Pevzner 2000;Zerbino and Birney 2008), and breakpoint graphs have had success in constructing rearrangement phylogeny across species, pioneered with several contributions from Sankoff and Pevzner (Sankoff and Blanchette 1999;Pevzner 2000;Bader and Ohlebusch 2007;Bader et al 2008;Alekseyev and Pevzner 2009;Warren and Sankoff 2009a,b). These methods have also been adapted to genomes containing duplications (Alekseyev and Pevzner 2007) and cancer (Raphael et al 2003;Raphael and Pevzner 2004;Ozery-Flato and Shamir 2009).…”

mentioning

confidence: 99%

Estimation of rearrangement phylogeny for cancer genomes

Greenman¹,

Pleasance²,

Newman³

et al. 2011

Genome Res.

111

135

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Cancer genomes are complex, carrying thousands of somatic mutations including base substitutions, insertions and deletions, rearrangements, and copy number changes that have been acquired over decades. Recently, technologies have been introduced that allow generation of high-resolution, comprehensive catalogs of somatic alterations in cancer genomes. However, analyses of these data sets generally do not indicate the order in which mutations have occurred, or the resulting karyotype. Here, we introduce a mathematical framework that begins to address this problem. By using samples with accurate data sets, we can reconstruct relatively complex temporal sequences of rearrangements and provide an assembly of genomic segments into digital karyotypes. For cancer genes mutated in rearranged regions, this information can provide a chronological examination of the selective events that have taken place.[Supplemental material is available for this article.]

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Breakpoint graphs and ancestral genome reconstructions

Cited by 121 publications

References 75 publications

Reconstruction and evolutionary history of eutherian chromosomes

Reconstruction and evolutionary history of eutherian chromosomes

Reference-assisted chromosome assembly

Estimation of rearrangement phylogeny for cancer genomes

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