Is mammalian chromosomal evolution driven by regions of genome fragility?

Ruiz‐Herrera, Aurora; Castresana, José; Robinson, Terence J.

doi:10.1186/gb-2006-7-12-r115

Cited by 133 publications

(89 citation statements)

References 72 publications

(100 reference statements)

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“…Because our models were derived and estimated using aCFSs initially defined by low-resolution cytogenetic methods, it was important to assess their predictive behavior for aCFSs mapped at higher resolution, i.e., with fluorescence probes around the breakage area (Ruiz-Herrera et al 2006). We were able to find high-resolution genomic coordinates of 18 autosomal cloned aCFS either using BAC accession numbers (Ciullo et al 2002;Fechter et al 2007;Reshmi et al 2007;Bosco et al 2010;Pelliccia et al 2010;Blumrich et al 2011) or data collected by Ruiz-Herrera and colleagues (Ruiz-Herrera et al 2006).…”

Section: Validation In Cloned Acfssmentioning

confidence: 86%

“…We were able to find high-resolution genomic coordinates of 18 autosomal cloned aCFS either using BAC accession numbers (Ciullo et al 2002;Fechter et al 2007;Reshmi et al 2007;Bosco et al 2010;Pelliccia et al 2010;Blumrich et al 2011) or data collected by Ruiz-Herrera and colleagues (Ruiz-Herrera et al 2006). Among these,14 (FRA2C,FRA2G,FRA2H,FRA3B,FRA4F,FRA6E,FRA6F,FRA7B,FRA7G,FRA7H,FRA9E,FRA11F,FRA11G, and FRA13A) overlapped with aCFSs cytogenetically defined by Mrasek and colleagues (Mrasek et al 2010), while high-resolution coordinates for the remaining four (FRA1E, FRA7E, FRA7I, and FRA16D) did not overlap with their cytogenetic coordinates (Supplemental Table S8).…”

Section: Validation In Cloned Acfssmentioning

confidence: 99%

“…T bands, a specific subset of R bands, have been shown to be sites of increased chromosomal rearrangement, both in cancer cells and during chromosomal evolution (Holmquist 1992). Interestingly, aCFSs may be depleted in evolutionarily homologous syntenic regions conserved between mammals and chicken (Ruiz-Herrera et al 2006).…”

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confidence: 99%

“…First, most studies considered only a few aCFSs, so the observed enrichment might not have reflected the global trend of genomic contexts surrounding such sites. Second, the studies analyzed the enrichment of single (and not multiple) genomic features at aCFSs, and compared these with control regions that differed from study to study (Mishmar et al 1998;Helmrich et al 2006;Ruiz-Herrera et al 2006;Tsantoulis et al 2008). Some of these studies previously used control regions that exhibited low-frequency breakage or were characterized as aCFSs in subsequent studies (Mrasek et al 2010).…”

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A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome?

et al. 2012

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Chromosomal common fragile sites (CFSs) are unstable genomic regions that break under replication stress and are involved in structural variation. They frequently are sites of chromosomal rearrangements in cancer and of viral integration. However, CFSs are undercharacterized at the molecular level and thus difficult to predict computationally. Newly available genome-wide profiling studies provide us with an unprecedented opportunity to associate CFSs with features of their local genomic contexts. Here, we contrasted the genomic landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of nonfragile sites, using multiple logistic regression. We also analyzed aCFS breakage frequencies as a function of their genomic landscape, using standard multiple regression. We show that local genomic features are effective predictors both of regions harboring aCFSs (explaining ∼81% of the deviance in logistic regression models) and of aCFS breakage frequencies (explaining ∼45% of the variance in standard regression models). In our optimal models (based on a combination of biological interpretability and high R-squared value), aCFSs are predominantly located in G-negative chromosomal bands and away from centromeres, are enriched in Alu repeats, and have high DNA flexibility. In alternative models, CpG island density, H3K4me1 coverage, and mononucleotide microsatellite coverage are significant predictors. Also, aCFSs have high fragility when colocated with evolutionarily conserved chromosomal breakpoints. Our models are predictive of the fragility of aCFSs mapped at a higher resolution. Importantly, the genomic features we identified here as significant predictors of fragility allow us to draw valuable inferences on the molecular mechanisms underlying aCFSs.

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Section: Validation In Cloned Acfssmentioning

confidence: 86%

Section: Validation In Cloned Acfssmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome?

et al. 2012

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“…Comparative sequence analysis in mammals and Drosophila species has subsequently provided evidence of breakpoint reuse (Murphy et al 2005;Ranz et al 2007). The cause of breakpoint reuse remains unclear, although it is frequently associated with sequences prone to participate in rearrangements, for example, segmental duplications (Bailey and Eichler 2006;Ruiz-Herrera et al 2006), or that confer fragility, for example, AT-rich regions (Strissel et al 1998;Zhang and Freudenreich 2007).…”

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Fragile regions and not functional constraints predominate in shaping gene organization in the genus Drosophila

Grotthuss¹,

Ashburner²,

Ranz³

2010

Genome Res.

135

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During evolution, gene repatterning across eukaryotic genomes is not uniform. Some genomic regions exhibit a gene organization conserved phylogenetically, while others are recurrently involved in chromosomal rearrangement, resulting in breakpoint reuse. Both gene order conservation and breakpoint reuse can result from the existence of functional constraints on where chromosomal breakpoints occur or from the existence of regions that are susceptible to breakage. The balance between these two mechanisms is still poorly understood. Drosophila species have very dynamic genomes and, therefore, can be very informative. We compared the gene organization of the main five chromosomal elements (Muller's elements A-E) of nine Drosophila species. Under a parsimonious evolutionary scenario, we estimate that 6116 breakpoints differentiate the gene orders of the species and that breakpoint reuse is associated with~80% of the orthologous landmarks. The comparison of the observed patterns of change in gene organization with those predicted under different simulated modes of evolution shows that fragile regions alone can explain the observed key patterns of Muller's element A (X chromosome) more often than for any other Muller's element. High levels of fragility plus constraints operating oñ 15% of the genome are sufficient to explain the observed patterns of change and conservation across species. The orthologous landmarks more likely to be under constraint exhibit both a remarkable internal functional heterogeneity and a lack of common functional themes with the exception of the presence of highly conserved noncoding elements. Fragile regions rather than functional constraints have been the main determinant of the evolution of the Drosophila chromosomes.

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Evolution of Common Fragile Sites

Helmrich

2008

Encyclopedia of Life Sciences

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Common fragile sites are specific deoxyribonucleic acid (DNA) breakage‐prone genomic regions in all healthy humans. Their instability is provoked by replication stress combined with an escape of cell cycle checkpoints. Common fragile sites are favoured regions of chromosomal aberration formation in the neoplastic process. They are inherent parts of the genomes of all so far analysed mammalian species, and recent data support their existence also in yeast. The common fragile site locations are highly conserved between human and other primates as well as between human and mouse. There is no evidence of an involvement of common fragile sites as ‘hotspots’ in chromosome evolution.

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Is mammalian chromosomal evolution driven by regions of genome fragility?

Abstract: An analysis of the distribution of evolutionary breakpoints in eight species suggests that certain human chromosomal regions are repeatedly used during the evolutionary process, are associated with fragile sites, and show an enrichment of tandem repeats.

Cited by 133 publications

References 72 publications

A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome?

A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome?

Fragile regions and not functional constraints predominate in shaping gene organization in the genus Drosophila

Evolution of Common Fragile Sites

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