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ABSTRACT:
PROVIDER: PRJNA1071349 | ENA |
REPOSITORIES: ENA
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Project description:This a model from the article:
Increased glycolytic flux as an outcome of whole-genome duplication in yeast.
Conant GC, Wolfe KH Mol. Syst. Biol.
[2007 ; Volume: 3 (Issue: )]: 129 17667951
,
Abstract:
After whole-genome duplication (WGD), deletions return most loci to single copy. However, duplicate loci may survive through selection for increased dosage. Here, we show how the WGD increased copy number of some glycolytic genes could have conferred an almost immediate selective advantage to an ancestor of Saccharomyces cerevisiae, providing a rationale for the success of the WGD. We propose that the loss of other redundant genes throughout the genome resulted in incremental dosage increases for the surviving duplicated glycolytic genes. This increase gave post-WGD yeasts a growth advantage through rapid glucose fermentation; one of this lineage's many adaptations to glucose-rich environments. Our hypothesis is supported by data from enzyme kinetics and comparative genomics. Because changes in gene dosage follow directly from post-WGD deletions, dosage selection can confer an almost instantaneous benefit after WGD, unlike neofunctionalization or subfunctionalization, which require specific mutations. We also show theoretically that increased fermentative capacity is of greatest advantage when glucose resources are both large and dense, an observation potentially related to the appearance of angiosperms around the time of WGD.
The original model submitted by the authors was slightly altered and now comprises the models originally submitted as MODEL2426780967, MODEL2427021978, MODEL2427095802. It reproduces figures 2A,3A and 3B from the publication.
This model uses the glycolysis model from Pritchard and Kell (2002) with an additional parameter, WGD_E
, to adjust for the differing enzyme conzentrations before the whole genome duplication (WGD) and parameters fV_xxx
that adjust the Vmax
of the different reactions (xxx eg. HXT or PYK).
Figure 3A from the article can be reproduced by changing the value of the parameters fV_xxx
to 0.9 indiviually, with xxx signifying the different enzymes (HXT, HXK ...)
Figure 3B from the publication can be reproduced by setting the parameter WGD_E
to 0.75 and individually setting the parameters fV_xxx
to 1.333.
To reproduce figure 2A from the article change the parameter WGD_E
in the range between 0.65 and 1.0.
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use
.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000176 | BioModels
Project description:This a model from the article:
Increased glycolytic flux as an outcome of whole-genome duplication in yeast.
Conant GC, Wolfe KH Mol. Syst. Biol.
[2007 ; Volume: 3 (Issue: )]: 129 17667951
,
Abstract:
After whole-genome duplication (WGD), deletions return most loci to single copy. However, duplicate loci may survive through selection for increased dosage. Here, we show how the WGD increased copy number of some glycolytic genes could have conferred an almost immediate selective advantage to an ancestor of Saccharomyces cerevisiae, providing a rationale for the success of the WGD. We propose that the loss of other redundant genes throughout the genome resulted in incremental dosage increases for the surviving duplicated glycolytic genes. This increase gave post-WGD yeasts a growth advantage through rapid glucose fermentation; one of this lineage's many adaptations to glucose-rich environments. Our hypothesis is supported by data from enzyme kinetics and comparative genomics. Because changes in gene dosage follow directly from post-WGD deletions, dosage selection can confer an almost instantaneous benefit after WGD, unlike neofunctionalization or subfunctionalization, which require specific mutations. We also show theoretically that increased fermentative capacity is of greatest advantage when glucose resources are both large and dense, an observation potentially related to the appearance of angiosperms around the time of WGD.
This model reproduces fig. 2C from the corrigendum
to the publication
The parameter Vmax_PDH
was corrected by a factor 60 from 6.32 mM/min in the publication to 379.2 mM/min in accordance with the authors.
see the corrigendum
at msb or its pubmed entry (pmid:18594520)
This model comprises the glycolysis model from Pritchard and Kell (2002) with an extension for the metabolisation of pyruvate in the mitochondria by pyruvate dehydrogenase and an additional parameter, WGD_E
, to adjust for the differing enzyme concentrations before the whole genome duplication (WGD).
To switch off transport of pyruvate to the mitochondria, set the parameter t_m
= 0.
Figure 2C from the article can be reproduced by manually changing the value of parameter WGD_E
in the range between 0.65 and 1.0 and calculating the ratios of ratio of PDC/PDH
fluxes in the altered model to the one of the model with WGD_E
= 1. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use
.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000177 | BioModels
Project description:High grade serous cancer (HGSC) is frequently characterizsed by homologous recombination (HR) DNA repair deficiency, and while most such tumours are sensitive to initial treatment, acquired resistance is common. We undertook a multi-omics approach to interrogating mechanisms of resistance, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. We observed frequent reversion mutations, resistance mechanisms restoring HR by other means, a high frequency of whole-genome duplication (WGD) suggestive of an evolutionary advantage, and global changes in immune composition with evidence of immune escape. Collectively these findings have implications for therapeutic intervention for HR-deficient HGSC.
2023-02-27 | PXD030034 | Pride
Project description:About 430 million years ago spiders and scorpions evolved from a common ancestor that had experienced a whole genome duplication (WGD) The genetic remnants of this WGD event (genes called ohnologs) can still be found in the genome of the approximately 45,000 species of these animals alive today and these ohnologs may have contributed to their adaptation and diversification. Interestingly, the WGD in arachnids like scorpions and spiders was contemporary with independent WGDs in vertebrates. This presents an opportunity to compare these events to determine if there are general principals underlying the outcomes of WGDs and their contribution to animal diversification. Therefore, the aims of this project are to identify arachnid ohnologs, explore how they have contributed to the evolutionary success of these animals, and compare the outcomes of this event to WGD in vertebrates. This includes sequencing new genomes and transcriptomes of species occupying key phylogenetic positions.
2023-11-21 | GSE241073 | GEO
Project description:Polyploidy or whole genome duplication (WGD) is a major event that drastically reshapes genome architecture and is often assumed to be causally associated with organismal innovations and radiations. The 2R Hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution. However, the timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved and whether these WGD events underlie vertebrate phenotypic diversification remains elusive. Here we present the genome of the inshore hagfish, Eptatretus burgeri. Through comparative analysis with lamprey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and the 2R event occurred in the gnathostome stem-lineage, maximally in the late Cambrian-earliest Ordovician, after its divergence from cyclostomes. We find that the genome of stem-cyclostomes experienced at least an additional, independent genome triplication. Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological diversification occurred only after the 2R event, questioning the general expectation that WGDs lead to leaps of bodyplan complexity.
2023-11-22 | GSE247552 | GEO
Project description:We developed an artificial genome evolution system, which we termed ‘TAQing’, by introducing multiple genomic DNA double-strand breaks using a heat-activatable endonuclease in Arabidopsis plant. The heat-activated endonuclease, TaqI, induced random DSBs, which resulted in diverse types of chromosomal rearrangements including translocations. To evaluate the potential of TAQing in multicellular organisms, we tested it in diploid and tetraploid Arabidopsis plants. In 9 out of 96 TQ4 plants, we detected 22 large copy number variations (CNVs) events compared witn wild type plant genome, whereas no CNV was found in the 16 control tetraploid plants, and 12 TQ2 plants. The combination of artificially introduced DSBs with whole-genome duplication (WGD) in plants enabled more complex genome reorganization.
2018-05-02 | GSE90026 | GEO
Project description:Triple-negative breast cancers (TNBC) account for 10-15% of all breast cancers. The combination of chemotherapy and Immunotherapy (ICI: immune checkpoint inhibitor) is now a standard in stages II-III TNBC while this regimen is used only in a subset of advanced TNBC tumors presenting a high expression of PD-L1. However, whole exome sequencing of tumors in clinical trials investigating ICI for treatment of various solid tumors other than breast cancer indicate that tumors which undergone a WGD (whole genome doubling) are more sensitive to immune checkpoints inhibitors. Almost all human cells are diploid. Nevertheless, a WGD happens when regulation system maintaining the diploid status fail. The WGD+ cells are tetraploid, oncogenic and facilitate tumorigenesis. The WGD occurs in 44% of breast cancers and has been correlated to advanced cases, lower survival and higher resistance to chemotherapies and targeted therapies. Therefore it is crucial todefine the role of WGD towards the immune escape/control of TNBC and response to ICI. The first step of this work was to generate different cells line in both WGD- and WGD+ status. Using a technique of membrane homofusion of parentals cells, we obtained a WGD in three different basal murine mammary tumor cell lines (67NR, 168fARN, TA3Hauschka) and one human TNBC cell (SUM 159). The acquisition of WGD was then confirmed by flow cytometry (FACS) (DNA quantity by Hoechst staining) and karyotyping. The TA3Hauschka cell line is of particular interest since it is the only murine cell line which is diploid in parental state. By injection of WGD+ or parental DP cells in mammary fat pads of syngeneic immunocompetent strain or immunocompromised (NSG) mice, we observed a plateau of tumoral growth only for immunocompetent mice injected with WGD- cells while the WGD+ tumors escaped to spontaneous immune control. No difference of growth was seen in NSG mice between WGD- and WGD+ tumors. On tumor sections, a much more pronounced necrosis was seen in WGD- tumors comparatively to WGD+ tumors in syngeneic mice while the necrosis was mild and similar for both WGD+ and WGD- tumors in NSG mice. Immunofluorescence staining demonstrated an important neutrophilic infiltration of WGD+ while the WGD- tumors had strong T-cell lymphoid infiltrates frankly superior to the lymphoid infiltration of WGD+ tumors. These differences of infiltrates have been confirmed on digested tumors by both FACS and single cells RNA expression (scRNA) analyses. The FACS analysis also showed that the WGD+ tumors had an immunosuppressive pattern with notably higher levels of Tregs cells. To validate the hypothesis that WGD- are controlled by the infiltration of cytotoxic CD8 cells (leading to higher necrosis) while WGD+ tumors induce an immunosuppressive field, we performed an in vivo experiment investigating depletion of CD8 and neutrophils (anti-CD8 and anti-Ly6G antibodies) and a treatment by anti-PD-L1 antibodies (ICI). The treatment by isotypes antibodies confirmed the immune control of only the WGD- tumors. Anti-CD8 treatment led to an important increase in WGD- tumors growth but hadn’t any impact on WGD+ tumors while anti-Ly6G antibodies had no significative impact on WGD- and WGD+ tumors. The treatment by anti-PD-L1 antibodies was significantly more efficient to reduce the growth of WGD+ tumors than WGD- tumors. ScRNA analysis of WGD- and WGD+ untreated tumors revealed that WGD+ tumors have a significative decrease of presentation of MHCI complex. Therefore, this study highlights the potential role of biomarker of response to immune checkpoint inhibitor of whole genome doubling in TNBC.
2026-03-15 | GSE273085 | GEO
Project description:Adult-type diffuse gliomas comprise IDH-mutant astrocytomas, IDH-mutant 1p/19q codeleted oligodendrogliomas (ODG), and IDH-wildtype glioblastomas (GBM). GBM display genome instability, which may result from two genetic events leading to massive chromosome alterations: chromothripsis (CT) and whole-genome duplication (WGD). The better prognosis of the latter may be related to their genome stability compared to GBM. Pangenomic profiles of 297 adult diffuse gliomas were analyzed at initial diagnosis using SNP arrays, including 192 GBM and 105 IDH-mutant gliomas (61 astrocytomas and 44 ODG). Tumor ploidy was assessed with Genome Alteration Print and CT events with CTLPScanner and through manual screening.
2024-12-24 | E-MTAB-13542 | biostudies-arrayexpress
Project description:Whole genome doubling (WGD) is one of the most common genetic alterations in human cancer generally associated with poor clinical outcome, yet the underlying mechanisms have not been delineated. Here we developed an experimental model of WGD using murine mammary tumor cell lines in immunocompetent mice and found that WGD triggers immune evasion characterized by reduced infiltration of CD8+ T cells. Via comprehensive cellular and molecular characterization of WGD+ and WGD- tumors at the single cell level, we determined that WGD+ cancer cells have diminished antigen presentation due to muted response to IFN stimulation in part due to epigenetic silencing of transcriptional regulators of MHCI genes via the PRC2 complex. WGD+ tumors also have lower alpha-ketoglutarate/succinate ratio that might lead to the observed increase in histone H3 lysine 27 trimethyl levels associated with repressive chromatin. Lastly, WGD+ tumors are more responsive to anti-PD-L1 blockade and to EED inhibitors and this is associated with increased antigen presentation and CD8+ T cell infiltration. Our results have important implications for the treatment of patients with WGD+ breast cancer.
2026-03-15 | GSE274160 | GEO
Project description:The genome of many plant and animal species are heavily influenced by ancestral whole genome duplication (WGD) events. These events transform the regulation and function of gene networks, yet the evolutionary forces at work on duplicated genomes are not fully understood. Genes involved in cell surface signaling pathways are commonly retained following WGD. To understand the mechanisms driving functional evolution of duplicated cell signaling pathways, we performed the activin receptor signaling pathway in rainbow trout (RBT). Rainbow trout are a model salmonid species that exhibit a duplicated genome as a result of an ancestral WGD that occurred in all teleost fish, and a second more recent WGD found in salmonid fishes. This makes RBT a powerful system for studying ohnolog evolution in a single species. We observed that regulation of the duplicated activin receptor signaling pathway is commonly driven by tissue-specific expression of inhibitors and ligands along with the subfunctionalization of ligand ohnologs. Evidence suggests that for inhibitors and R-Smad signaling molecules, there is ongoing pressure to establish a single copy state which may be driven, in part, by regulatory suppression of select ohnologs. The core transmembrane receptors and Co-Smad signaling cascade members are high duplicated yet exhibit contrasting expression dynamics where receptors tend to share expression across tissues while dominance of a single ohnolog is common for the Smad4, Co-Smad gene family. Our findings provide support for a generalized model where gene function and gene dosage have a complementary role in ohnolog evolution following WGD.
2023-02-07 | GSE224617 | GEO