Structural organization of human replication timing domains

AbstractRecent analysis of genome-wide epigenetic modification data, mean replication timing (MRT) profiles and chromosome conformation data in mammals have provided increasing evidence that flexibility in replication origin usage is regulated locally by the epigenetic landscape and over larger genomic distances by the 3D chromatin architecture. Here, we review the recent results establishing some link between replication domains and chromatin structural domains in pluripotent and various differentiated cell types in human. We reconcile the originally proposed dichotomic picture of early and late constant timing regions that replicate by multiple rather synchronous origins in separated nuclear compartments of open and closed chromatins, with the U-shaped MRT domains bordered by “master” replication origins specified by a localized (∼200–300kb) zone of open and transcriptionally active chromatin from which a replication wave likely initiates and propagates toward the domain center via a cascade of origin firing. We discuss the relationships between these MRT domains, topologically associated domains and lamina-associated domains. This review sheds a new light on the epigenetically regulated global chromatin reorganization that underlies the loss of pluripotency and the determination of differentiation properties

Reconstruction of ancestral chromosome architecture and gene repertoire reveals principles of genome evolution in a model yeast genus

International audienceReconstructing genome history is complex but necessary to reveal quantitative principles governing genome evolution. Such reconstruction requires recapitulating into a single evolutionary framework the evolution of genome architecture and gene repertoire. Here, we reconstructed the genome history of the genus Lachancea that appeared to cover a continuous evolutionary range from closely related to more diverged yeast species. Our approach integrated the generation of a high-quality genome data set; the development of AnChro, a new algorithm for reconstructing ancestral genome architecture; and a comprehensive analysis of gene repertoire evolution. We found that the ancestral genome of the genus Lachancea contained eight chromosomes and about 5173 protein-coding genes. Moreover, we characterized 24 horizontal gene transfers and 159 putative gene creation events that punctuated species diversification. We retraced all chromosomal rearrangements, including gene losses, gene duplications, chromosomal inversions and translocations at single gene resolution. Gene duplications outnumbered losses and balanced rearrangements with 1503, 929, and 423 events, respectively. Gene content variations between extant species are mainly driven by differential gene losses, while gene duplications remained globally constant in all lineages. Remarkably, we discovered that balanced chromosomal rearrangements could be responsible for up to 14% of all gene losses by disrupting genes at their breakpoints. Finally, we found that nonsynonymous substitutions reached fixation at a coordinated pace with chromosomal inversions, translocations, and duplications, but not deletions. Overall, we provide a granular view of genome evolution within an entire eukaryotic genus, linking gene content, chromosome rearrangements , and protein divergence into a single evolutionary framework

Analyse combinatoire des réarrangements chromosomiques et reconstruction des génomes ancestraux chez les eucaryotes

PARIS-BIUSJ-Mathématiques rech (751052111) / SudocSudocFranceF

Combinatorics of chromosomal rearrangements based on synteny blocks and synteny packs

International audienceThe reconstruction of the history of rearrangements and the reconstruction of ancestral genomes are some of the challenges of bioinformatics today. Many algorithms already exist, treating one or the other question but none treating both. These reconstructions are interdependent and we argue on the interest of treating both problems in parallel to lead to a richer and more complete output. We also argue on the importance of redefining several steps of these algorithms to improve both reconstructions: the identification of synteny blocks has to be as precise as possible, and the treatment of multiple genomes has to be based on pairwise comparisons to ensure the most detailed reconstructions. In this article, we highlight novel solutions to these points and focus on the need of explicitly treating overlapping, included, duplicated and unsigned synteny blocks. To do so, we introduce the new notion of synteny pack, which is a representation of local hypothetical intermediate ancestral genomes. We discuss a number of examples on yeast genomes to illustrate the importance of such a definition

SynChro: A Fast and Easy Tool to Reconstruct and Visualize Synteny Blocks along Eukaryotic Chromosomes

International audienceReconstructing synteny blocks is an essential step in comparative genomics studies. Different methods were already developed to answer various needs such as genome (re-)annotation, identification of duplicated regions and whole genome duplication events or estimation of rearrangement rates. We present SynChro, a tool that reconstructs synteny blocks between pairwise comparisons of multiple genomes. SynChro is based on a simple algorithm that computes Reciprocal Best-Hits (RBH) to reconstruct the backbones of the synteny blocks and then automatically completes these blocks with non-RBH syntenic homologs. This approach has two main advantages: (i) synteny block reconstruction is fast (feasible on a desk computer for large eukaryotic genomes such as human) and (ii) synteny block reconstruction is straightforward as all steps are integrated (no need to run Blast or TribeMCL prior to reconstruction) and there is only one parameter to set up, the synteny block stringency . Benchmarks on three pairwise comparisons of genomes, representing three different levels of synteny conservation (Human/Mouse, Human/Zebra Finch and Human/Zebrafish) show that Synchro runs faster and performs at least as well as two other commonly used and more sophisticated tools (MCScanX and i-ADHoRe). In addition, SynChro provides the user with a rich set of graphical outputs including dotplots, chromosome paintings and detailed synteny maps to visualize synteny blocks with all homology relationships and synteny breakpoints with all included genetic features

Characteristics of SynChro, MCScanX and i-ADHoRe synteny blocks for three pairwise comparisons.

<p>The execution time (in minutes) indicates the time used for homolog identification and for synteny block reconstruction (for SynChro, these two steps are not really separable because reconstruction of synteny blocks implies the identification of additional non-RBH homologs by blastp). The number of syntenic homologs represents the total number of homology relationships in the synteny blocks. The numbers between brackets indicate the number of homology relationships when only one relationship per gene per synteny block is allowed (<i>i.e</i>. removing the homology relationships corresponding to tandemly duplicated genes within a given synteny block). Note that for MCScanX these 2 values are identical because the program was run with the option which prevents MCScanX to detect tandemly duplicated genes within a given synteny block.</p

SynChro algorithm, inputs and outputs.

<p>The format of input files are indicated in the blue frame. The different steps of the algorithm are illustrated in the black frame (colored dots symbolize genes, green and red plain lines highlight RBH relationships and dotted lines represent non-RBH homologous relationships). In step 1, all RBH gene-pairs are mapped regardless of their chromosomal positions, in step 2 only the syntenic RBH-pairs are mapped and in step 3 the non-RBH syntenic homologs are added to the map. The different types of outputs are shown in the orange frames.</p

Congruence between the 3 different synteny block reconstructions.

<p>An example based on a segment of the <i>Homo sapiens</i>' X chromosome (from coordinates 53,078 to 114,468 kb) and the genome of <i>Mus musculus</i> is presented. The synteny blocks reconstructed by the three tools, SynChro, MCScanX and iADHoRe are represented by red, blue and green-framed open boxes, respectively. The two coordinates, inside each box, refer to the coordinates in the mouse genome. Synteny blocks from 2 different reconstructions are congruent when overlaping synteny blocks, along the human chromosome X, map overlapping regions in the mouse genome. These congruent synteny blocks are represented by hatched bi-colored boxes and are denoted: SynChroMCScanX, MCScanXi-ADHoRe and SynChroi-ADHoRe. The intersection of these three sets of synteny blocks allows to define regions (such as regions 1, 3 and 8) where the three tools are in agreements (tri-colored hatched boxes) and to deduce regions (such as the other regions) where only one or two tools detect synteny conservation (or are in agreement). The 5 lines at the bottom of the figure summarize these regions. Note that overlapping synteny blocks predicted by MCSanX or i-ADHoRe correspond to regions containing duplicated genes between the blocks. These regions do not necessarily contain many duplicated genes given that a single duplicate is sufficient to produce an overlap.</p

Genome-Based Analyses of Six Hexacorallian Species Reject the "Naked Coral" Hypothesis

Scleractinian corals are the foundation species of the coral-reef ecosystem. Their calcium carbonate skeletons form extensive structures that are home to millions of species, making coral reefs one of the most diverse ecosystems of our planet. However, our understanding of how reef-building corals have evolved the ability to calcify and become the ecosystem builders they are today is hampered by uncertain relationships within their subclass Hexacorallia. Corallimorpharians have been proposed to originate from a complex scleractinian ancestor that lost the ability to calcify in response to increasing ocean acidification, suggesting the possibility for corals to lose and gain the ability to calcify in response to increasing ocean acidification. Here, we employed a phylogenomic approach using whole-genome data from six hexacorallian species to resolve the evolutionary relationship between reef-building corals and their noncalcifying relatives. Phylogenetic analysis based on 1,421 single-copy orthologs, as well as gene presence/absence and synteny information, converged on the same topologies, showing strong support for scleractinian monophyly and a corallimorpharian sister clade. Our broad phylogenomic approach using sequence-based and sequence-independent analyses provides unambiguous evidence for the monophyly of scleractinian corals and the rejection of corallimorpharians as descendants of a complex coral ancestor.publishe

Evidence for DNA Sequence Encoding of an Accessible Nucleosomal Array across Vertebrates

Nucleosome-depleted regions around which nucleosomes order following the ''statistical'' positioning scenario were recently shown to be encoded in the DNA sequence in human. This intrinsic nucleosomal ordering strongly correlates with oscillations in the local GC content as well as with the interspecies and intraspecies mutation profiles, revealing the existence of both positive and negative selection. In this letter, we show that these predicted nucleosome inhibitory energy barriers (NIEBs) with compacted neighboring nucleosomes are indeed ubiquitous to all vertebrates tested. These 1 kb-sized chromatin patterns are widely distributed along vertebrate chromosomes, overall covering more than a third of the genome. We have previously observed in human deviations from neutral evolution at these genome-wide distributed regions, which we interpreted as a possible indication of the selection of an open, accessible, and dynamic nucleosomal array to constitutively facilitate the epigenetic regulation of nuclear functions in a cell-type-specific manner. As a first, very appealing observation supporting this hypothesis, we report evidence of a strong association between NIEB borders and the poly(A) tails of Alu sequences in human. These results suggest that NIEBs provide adequate chromatin patterns favorable to the integration of Alu retrotransposons and, more generally to various transposable elements in the genomes of primates and other vertebrates.Méthodes de peignage moléculaire à haut débit pour une cartographie rapide de la réplication du génome humainDynamiques eco-évolutives des maladies infectieuse