The rise and fall of breakpoint reuse depending on genome resolution

<p>Abstract</p> <p>Background</p> <p>During evolution, large-scale genome rearrangements of chromosomes shuffle the order of homologous genome sequences ("synteny blocks") across species. Some years ago, a controversy erupted in genome rearrangement studies over whether rearrangements recur, causing breakpoints to be reused.</p> <p>Methods</p> <p>We investigate this controversial issue using the synteny block's for human-mouse-rat reported by Bourque <it>et al</it>. and a series of synteny blocks we generated using Mauve at resolutions ranging from coarse to very fine-scale. We conducted analyses to test how resolution affects the traditional measure of the breakpoint reuse rate<it>.</it></p> <p>Results</p> <p>We found that the inversion-based breakpoint reuse rate is low at fine-scale synteny block resolution and that it rises and eventually falls as synteny block resolution decreases. By analyzing the cycle structure of the breakpoint graph of human-mouse-rat synteny blocks for human-mouse and comparing with theoretically derived distributions for random genome rearrangements, we showed that the implied genome rearrangements at each level of resolution become more “random” as synteny block resolution diminishes. At highest synteny block resolutions the Hannenhalli-Pevzner inversion distance deviates from the Double Cut and Join distance, possibly due to small-scale transpositions or simply due to inclusion of erroneous synteny blocks. At synteny block resolutions as coarse as the Bourque <it>et al</it>. blocks, we show the breakpoint graph cycle structure has already converged to the pattern expected for a random distribution of synteny blocks.</p> <p>Conclusions</p> <p>The inferred breakpoint reuse rate depends on synteny block resolution in human-mouse genome comparisons. At fine-scale resolution, the cycle structure for the transformation appears less random compared to that for coarse resolution. Small synteny blocks may contain critical information for accurate reconstruction of genome rearrangement history and parameters.</p

Breaking Good: Accounting For Fragility Of Genomic Regions In Rearrangement Distance Estimation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Models of evolution by genome rearrangements are prone to two types of flaws: One is to ignore the diversity of susceptibility to breakage across genomic regions, and the other is to suppose that susceptibility values are given. Without necessarily supposing their precise localization, we call "solid" the regions that are improbably broken by rearrangements and "fragile" the regions outside solid ones. We propose a model of evolution by inversions where breakage probabilities vary across fragile regions and over time. It contains as a particular case the uniform breakage model on the nucleotidic sequence, where breakage probabilities are proportional to fragile region lengths. This is very different from the frequently used pseudouniform model where all fragile regions have the same probability to break. Estimations of rearrangement distances based on the pseudouniform model completely fail on simulations with the truly uniform model. On pairs of amniote genomes, we show that identifying coding genes with solid regions yields incoherent distance estimations, especially with the pseudouniform model, and to a lesser extent with the truly uniform model. This incoherence is solved when we coestimate the number of fragile regions with the rearrangement distance. The estimated number of fragile regions is surprisingly Small, suggesting that a minority of regions are recurrently used by rearrangements. Estimations for several pairs of genomes at different divergence times are in agreement with a slowly evolvable colocalization of active genomic regions in the cell.8514271439FAPESP [2013/25084-2]French Agence Nationale de la Recherche (ANR) [ANR-10-BINF-01-01]ICT FP7 european programme EVOEVOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Breaking Good: Accounting for Fragility of Genomic Regions in Rearrangement Distance Estimation

International audienceModels of evolution by genome rearrangements are prone to two types of flaws: One is to ignore the diversity of susceptibility tobreakage across genomic regions, and the other is to suppose that susceptibility values are given. Without necessarily supposing theirprecise localization,we call “solid” the regions that are improbably broken by rearrangements and “fragile” the regions outside solidones.We propose a model of evolution by inversions where breakage probabilities vary across fragile regions and over time. It containsas a particular case the uniform breakage model on the nucleotidic sequence,where breakage probabilities are proportional to fragileregion lengths. This is very different from the frequently used pseudo uniform model where all fragile regions have the same probabilityto break. Estimations of rearrangement distances based on the pseudo uniform model completely fail on simulations with thetruly uniform model. On pairs of amniote genomes, we show that identifying coding genes with solid regions yields incoherentdistance estimations, especially with the pseudo uniform model, and to a lesser extent with the truly uniform model. This incoherenceis solved when we coestimate the number of fragile regions with the rearrangement distance. The estimated number of fragileregions is surprisingly small, suggesting that a minority of regions are recurrently used by rearrangements. Estimations for several pairsof genomes at different divergence times are in agreement with a slowly evolvable colocalization of active genomic regions in the cell