scholarly journals An evolutionary model identifies the main evolutionary biases for the evolution of genome-replication profiles

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rossana Droghetti ◽  
Nicolas Agier ◽  
Gilles Fischer ◽  
Marco Gherardi ◽  
Marco Cosentino Lagomarsino
Keyword(s):  
Replication Origin ◽  
Yeast Species ◽  
Evolutionary Model ◽  
Replication Timing ◽  
Death Process ◽  
Genome Replication ◽  
Replication Forks ◽  
Evolutionary Models ◽  
Replication Origins ◽  
Evolutionary Studies

Recent results comparing the temporal program of genome replication of yeast species belonging to the Lachancea clade support the scenario that the evolution of replication timing program could be mainly driven by correlated acquisition and loss events of active replication origins. Using these results as a benchmark, we develop an evolutionary model defined as birth-death process for replication origins, and use it to identify the evolutionary biases that shape the replication timing profiles. Comparing different evolutionary models with data, we find that replication origin birth and death events are mainly driven by two evolutionary pressures, the first imposes that events leading to higher double-stall probability of replication forks are penalized, while the second makes less efficient origins more prone to evolutionary loss. This analysis provides an empirically grounded predictive framework for quantitative evolutionary studies of the replication timing program.

scholarly journals An evolutionary model identifies the main selective pressures for the evolution of genome-replication profiles

2020 ◽  
Author(s):  
Rossana Droghetti ◽  
Nicolas Agier ◽  
Gilles Fischer ◽  
Marco Gherardi ◽  
Marco Cosentino Lagomarsino
Keyword(s):  
Yeast Species ◽  
Evolutionary Model ◽  
Replication Timing ◽  
Death Process ◽  
Genome Replication ◽  
Replication Forks ◽  
Evolutionary Models ◽  
Replication Origins ◽  
Selective Pressures ◽  
Evolutionary Studies

AbstractRecent results comparing the temporal program of genome replication of yeast species belonging to the Lachancea clade support the scenario that the evolution of replication timing program could be mainly driven by correlated acquisition and loss events of active replication origins. Using these results as a benchmark, we develop an evolutionary model defined as birth-death process for replication origins, and use it to identify the selective pressures that shape the replication timing profiles. Comparing different evolutionary models with data, we find that replication origin birth and death events are mainly driven by two evolutionary pressures, the first imposes that events leading to higher double-stall probability of replication forks are penalized, while the second makes less efficient origins more prone to evolutionary loss. This analysis provides an empirically grounded predictive framework for quantitative evolutionary studies of the replication timing program.

scholarly journals Dynamics of replication origin over-activation

2020 ◽  
Author(s):  
Haiqing Fu ◽  
Christophe E. Redon ◽  
Koichi Utani ◽  
Bhushan L. Thakur ◽  
Sangmin Jang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Molecular Interactions ◽  
Replication Origin ◽  
Replication Timing ◽  
Replication Stress ◽  
Single Fiber ◽  
Replication Origins ◽  
Initiation Frequency

AbstractWe determined replication patterns in cancer cells in which the controls that normally prevent excess replication were disrupted (“re-replicating cells”). Single-fiber analyses suggested that replication origins were activated at a higher frequency in re-replicating cells. However, nascent strand sequencing demonstrated that re-replicating cells utilized the same pool of potential replication origins as normally replicating cells. Surprisingly, re-replicating cells exhibited a skewed initiation frequency correlating with replication timing. These patterns differed from the replication profiles observed in non-re-replicating cells exposed to replication stress, which activated a novel group of dormant origins not typically activated during normal mitotic growth. Hence, disruption of the molecular interactions that regulates origin initiation can activate two distinct pools of potential replication origins: re-replicating cells over-activate flexible origins while replication stress in normal mitotic growth activates dormant origins.

scholarly journals Unreplicated DNA remaining from unperturbed S phases passes through mitosis for resolution in daughter cells

2016 ◽  
Vol 113 (39) ◽  
pp. E5757-E5764 ◽  
Author(s):  
Alberto Moreno ◽  
Jamie T. Carrington ◽  
Luca Albergante ◽  
Mohammed Al Mamun ◽  
Emma J. Haagensen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Eukaryotic Cell ◽  
Nuclear Bodies ◽  
Genome Replication ◽  
Replication Forks ◽  
Replication Origins ◽  
Theoretical Predictions ◽  
Fork Stalling ◽  
Theoretical Evidence ◽  
Pass Through

To prevent rereplication of genomic segments, the eukaryotic cell cycle is divided into two nonoverlapping phases. During late mitosis and G1 replication origins are “licensed” by loading MCM2-7 double hexamers and during S phase licensed replication origins activate to initiate bidirectional replication forks. Replication forks can stall irreversibly, and if two converging forks stall with no intervening licensed origin—a “double fork stall” (DFS)—replication cannot be completed by conventional means. We previously showed how the distribution of replication origins in yeasts promotes complete genome replication even in the presence of irreversible fork stalling. This analysis predicts that DFSs are rare in yeasts but highly likely in large mammalian genomes. Here we show that complementary strand synthesis in early mitosis, ultrafine anaphase bridges, and G1-specific p53-binding protein 1 (53BP1) nuclear bodies provide a mechanism for resolving unreplicated DNA at DFSs in human cells. When origin number was experimentally altered, the number of these structures closely agreed with theoretical predictions of DFSs. The 53BP1 is preferentially bound to larger replicons, where the probability of DFSs is higher. Loss of 53BP1 caused hypersensitivity to licensing inhibition when replication origins were removed. These results provide a striking convergence of experimental and theoretical evidence that unreplicated DNA can pass through mitosis for resolution in the following cell cycle.

scholarly journals The evolution of the temporal program of genome replication

2017 ◽  
Author(s):  
Nicolas Agier ◽  
Stéphane Delmas ◽  
Qing Zhang ◽  
Aubin Fleiss ◽  
Yan Jaszczyszyn ◽  
...  
Keyword(s):  
Related Species ◽  
Replication Timing ◽  
Evolutionary Divergence ◽  
Genome Replication ◽  
Last Common Ancestor ◽  
Replication Origins ◽  
Active Replication ◽  
Firing Efficiency ◽  
Gains And Losses ◽  
Temporal Program

AbstractComparative analyses of temporal programs of genome replication revealed either a nearly complete conservation between closely related species or a comprehensive reprogramming between distantly related species. Therefore, many important questions on the evolutionary remodeling of replication timing programs remain unanswered. To address this issue, we generated genome-wide replication timing profiles for ten yeast species from the genus Lachancea, covering a continuous evolutionary range from closely related to more divergent species. The comparative analysis of these profiles revealed that the replication program linearly evolves with increasing evolutionary divergence between these species. We found that the evolution of the timing program mainly results from a high evolutionary turnover rate of the cohort of active replication origins. We detected about one thousand evolutionary events of losses of active replication origins and gains of newborn origins since the species diverged from their last common ancestor about 80 million years ago. We show that the relocation of active replication origins is independent from synteny breakpoints, suggesting that chromosome rearrangements did not drive the evolution of the replication programs. Rather, origin gains and losses are linked both in space, along chromosomes, and in time, along the same branches of the phylogenetic tree. New origins continuously arise with on average low to medium firing efficiencies and increase in efficiency and earliness as they evolutionarily age. Yet, a subset of newborn origins emerges with high firing efficiency and origin losses occur concomitantly to their emergence and preferentially in their direct chromosomal vicinity. These key findings on the evolutionary birth, death and conservation of active replication origins provide the first description of how the temporal program of genome replication has evolved in eukaryotes.

scholarly journals The Remarkable Evolution of the Post-Agb Star FG SGE

1998 ◽  
Vol 11 (1) ◽  
pp. 363-363
Author(s):  
Johanna Jurcsik ◽  
Benjamin Montesinos
Keyword(s):  
Time Scales ◽  
Effective Temperature ◽  
Planetary Nebula ◽  
Planetary Nebulae ◽  
Central Star ◽  
Evolutionary Models ◽  
Single Star ◽  
Line Intensities ◽  
Evolutionary Changes ◽  
Evolutionary Studies

FG Sagittae is one of the most important key objects of post-AGB stellar evolutionary studies. As a consequence of a final helium shell flash, this unique variable has shown real evolutionary changes on human time scales during this century. The observational history was reviewed in comparison with predictions from evolutionary models. The central star of the old planetary nebula (Hel-5) evolved from left to right in the HR diagram, going in just hundred years from the hot region of exciting sources of planetary nebulae to the cool red supergiant domain just before our eyes becoming a newly-born post-AGB star. The effective temperature of the star was around 50,000 K at the beginning of this century, and the last estimates in the late 1980s give 5,000-6,500 K. Recent spectroscopic observations obtained by Ingemar Lundström show definite changes in the nebular line intensities. This fact undoubtedly rules out the possibility that, instead of FG Sge, a hidden hot object would be the true central star of the nebula. Consequently, the observed evolutionary changes are connected with the evolution of a single star.

scholarly journals Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongzheng Li ◽  
Boxin Xue ◽  
Mengling Zhang ◽  
Liwei Zhang ◽  
Yingping Hou ◽  
...  
Keyword(s):  
Dna Replication ◽  
Structural Dynamics ◽  
Replication Origin ◽  
High Efficiency ◽  
S Phase ◽  
Chromatin Domain ◽  
Replication Origins ◽  
Replication Efficiency ◽  
Topologically Associating Domains ◽  
Epigenetic Signatures

Abstract Background Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined. Results We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired. Conclusion Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.

scholarly journals Investigation of the Interaction of Human Origin Recognition Complex Subunit 1 with G-Quadruplex DNAs of Human c-myc Promoter and Telomere Regions

2021 ◽  
Vol 22 (7) ◽  
pp. 3481
Author(s):  
Afaf Eladl ◽  
Yudai Yamaoki ◽  
Shoko Hoshina ◽  
Haruka Horinouchi ◽  
Keiko Kondo ◽  
...  
Keyword(s):  
Fluorescence Anisotropy ◽  
Binding Sites ◽  
Replication Origin ◽  
Origin Recognition Complex ◽  
Chemical Shift Perturbation ◽  
Human Origin ◽  
Replication Origins ◽  
Genome Wide ◽  
G Quadruplex ◽  
Origin Recognition

Origin recognition complex (ORC) binds to replication origins in eukaryotic DNAs and plays an important role in replication. Although yeast ORC is known to sequence-specifically bind to a replication origin, how human ORC recognizes a replication origin remains unknown. Previous genome-wide studies revealed that guanine (G)-rich sequences, potentially forming G-quadruplex (G4) structures, are present in most replication origins in human cells. We previously suggested that the region comprising residues 413–511 of human ORC subunit 1, hORC1413–511, binds preferentially to G-rich DNAs, which form a G4 structure in the absence of hORC1413–511. Here, we investigated the interaction of hORC1413-511 with various G-rich DNAs derived from human c-myc promoter and telomere regions. Fluorescence anisotropy revealed that hORC1413–511 binds preferentially to DNAs that have G4 structures over ones having double-stranded structures. Importantly, circular dichroism (CD) and nuclear magnetic resonance (NMR) showed that those G-rich DNAs retain the G4 structures even after binding with hORC1413–511. NMR chemical shift perturbation analyses revealed that the external G-tetrad planes of the G4 structures are the primary binding sites for hORC1413–511. The present study suggests that human ORC1 may recognize replication origins through the G4 structure.

scholarly journals High-throughput analysis of DNA replication in single human cells reveals constrained variability in the location and timing of replication initiation

2021 ◽  
Author(s):  
Dashiell J Massey ◽  
Amnon Koren
Keyword(s):  
Dna Replication ◽  
Replication Origin ◽  
Replication Timing ◽  
S Phase ◽  
Human Cells ◽  
Replication Initiation ◽  
High Throughput Analysis ◽  
Timing Variability ◽  
Fixed Set ◽  
Fixed Order

DNA replication occurs throughout the S phase of the cell cycle, initiating from replication origin loci that fire at different times. Debate remains about whether origins are a fixed set of loci used across all cells or a loose agglomeration of potential origins used stochastically in individual cells, and about how consistent their firing time during S phase is across cells. Here, we develop an approach for profiling DNA replication in single human cells and apply it to 2,305 replicating cells spanning the entire S phase. The resolution and scale of the data enabled us to specifically analyze initiation sites and show that these sites have confined locations that are consistently used among individual cells. Further, we find that initiation sites are activated in a similar, albeit not fixed, order across cells. Taken together, our results suggest that replication timing variability is constrained both spatially and temporally, and that the degree of variation is consistent across human cell lines.

scholarly journals Studying 3D genome evolution using genomic sequence

2019 ◽  
Author(s):  
Raphaël Mourad
Keyword(s):  
Genome Evolution ◽  
Genomic Sequence ◽  
Regulation Of Gene Expression ◽  
Replication Timing ◽  
Evolutionary Constraints ◽  
3D Genome ◽  
Chromatin Looping ◽  
Novel Approach ◽  
Evolutionary Studies ◽  
Ancestral Character Reconstruction

AbstractThe 3D genome is essential to numerous key processes such as the regulation of gene expression and the replication-timing program. In vertebrates, chromatin looping is often mediated by CTCF, and marked by CTCF motif pairs in convergent orientation. Comparative Hi-C recently revealed that chromatin looping evolves across species. However, Hi-C experiments are complex and costly, which currently limits their use for evolutionary studies over a large number of species. Here, we propose a novel approach to study the 3D genome evolution in vertebrates using the genomic sequence only, e.g. without the need for Hi-C data. The approach is simple and relies on comparing the distances between convergent and divergent CTCF motifs (ratio R). We show that R is a powerful statistic to detect CTCF looping encoded in the human genome sequence, thus reflecting strong evolutionary constraints encoded in DNA and associated with the 3D genome. When comparing vertebrate genomes, our results reveal that R which underlies CTCF looping and TAD organization evolves over time and suggest that ancestral character reconstruction can be used to infer R in ancestral genomes.

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