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.
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.
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.
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.
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.
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.
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.
Project description:Whole genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies. However, the 3D organization of the chromatin in WGD cells and its contribution to oncogenic phenotypes are currently unknown. Here, we show that in p53 deficient cells WGD induces loss of chromatin segregation (LCS), characterized by reduced segregation between short and long chromosomes, A and B sub-compartments, and adjacent chromatin domains. LCS is driven by downregulation of CTCF and H3K9me3 in cells that bypassed activation of the tetraploid checkpoint. Longitudinal analyses revealed that LCS primed genomic regions for sub-compartment repositioning in WGD cells, which resulted in chromatin and epigenetic changes associated with oncogene activation in tumours ensuing from WGD cells. Importantly, sub-compartment repositioning events were largely independent of chromosomal alterations, indicating that these were complementary mechanisms contributing to tumour development and progression. Overall, LCS initiates chromatin conformation changes that ultimately result in oncogenic epigenetic and transcriptional modifications, suggesting that chromatin evolution is a hallmark of WGD-driven cancer.
Project description:We set out to determine how Sfp1 binding targets evolved over time. We sampled our species of interest to include one pre-whole genome duplicaton (WGD) species containing SFP1A (K. lactis), one post-WGD species containing both SFP1 and SFP1PL (N. castellii), two post-WGD species containing only SFP1 (S. cerevisiae and S. paradoxus) and performed ChIP for each Sfp1 homolog in each species using an antibody that recognizes a conserved subdomain of Sfp1 common to both Sfp1, Sfp1a, and Sfp1pl. Because Sfp1pl was also present in N. castellii, a second antibody was used that is more specific to Sfp1pl (denoted as IP3). We also performed ChIP in SFP1 deletion mutants in each species tested, as a control."
Project description:Polyploidy or whole genome duplication (WGD) provides raw genetic materials for sequence and expression evolution of duplicate genes. However, the mode and tempo of expression divergence between WGD duplicate genes in closely relates species and recurrent allopolyploids are poorly understood. Arabidopsis is a suitable system for testing the hypothesis that duplicate genes increase expression diversity and regulatory networks. In Arabidopsis, WGD occurred more than once prior to the split between Arabidopsis thaliana and Arabidopsis arenosa, and both natural and human-made allotetraploids are available. Comparative genomic hybridization analysis indicated that single-copy and duplicate genes after WGD were well preserved in A. thaliana and A. arenosa. Analysis of gene expression microarrays showed that duplicate genes generally had higher levels of expression divergence between two closely related species than single-copy genes. The proportion of the progenitors' duplicate genes that were nonadditively expressed in the resynthesized and natural allotetraploids was significantly higher than that of single-copy genes. Duplicate genes related to environmental stresses tended to be differentially expressed, and multi-copy duplicate genes were likely to diverge expression between progenitors and in the allotetraploids. Compared to single-copy genes, duplicate genes tend to contain TATA boxes and less DNA methylation in the promoter regions, facilitating transcriptional regulation by binding transcription factors and/or cis-and trans- acting proteins. The data suggest an important role of WGD duplicate genes in modulating diverse and novel gene expression changes in response to external environmental cues as well as internal genetic turmoil such as recurrent polyploidy events.