| 1. |
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| 2. |
- Ament-Velásquez, S. Lorena, Ph.D. 1988-, et al.
(författare)
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Allorecognition genes drive reproductive isolation in Podospora anserina
- 2022
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Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 6:7, s. 910-923
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Tidskriftsartikel (refereegranskat)abstract
- Allorecognition, the capacity to discriminate self from conspecific non-self, is a ubiquitous organismal feature typically governed by genes evolving under balancing selection. Here, we show that in the fungus Podospora anserina, allorecognition loci controlling vegetative incompatibility (het genes), define two reproductively isolated groups through pleiotropic effects on sexual compatibility. These two groups emerge from the antagonistic interactions of the unlinked loci het-r (encoding a NOD-like receptor) and het-v (encoding a methyltransferase and an MLKL/HeLo domain protein). Using a combination of genetic and ecological data, supported by simulations, we provide a concrete and molecularly defined example whereby the origin and coexistence of reproductively isolated groups in sympatry is driven by pleiotropic genes under balancing selection.
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| 3. |
- Ament-Velásquez, Sandra Lorena, M.Sc. 1988-, et al.
(författare)
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The taxonomy of the model filamentous fungus Podospora anserina
- 2020
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Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; :75, s. 51-69
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Tidskriftsartikel (refereegranskat)abstract
- The filamentous fungus Podospora anserina has been used as a model organism for more than 100 years and has proved to be an invaluable resource in numerous areas of research. Throughout this period, P. anserina has been embroiled in a number of taxonomic controversies regarding the proper name under which it should be called. The most recent taxonomic treatment proposed to change the name of this important species to Triangularia anserina. The results of past name changes of this species indicate that the broader research community is unlikely to accept this change, which will lead to nomenclatural instability and confusion in literature. Here, we review the phylogeny of the species closely related to P. anserina and provide evidence that currently available marker information is insufficient to resolve the relationships amongst many of the lineages. We argue that it is not only premature to propose a new name for P. anserina based on current data, but also that every effort should be made to retain P. anserina as the current name to ensure stability and to minimise confusion in scientific literature. Therefore, we synonymise Triangularia with Podospora and suggest that either the type species of Podospora be moved to P. anserina from P. fimiseda or that all species within the Podosporaceae be placed in the genus Podospora.
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| 4. |
- Femel, Julia, 1986-, et al.
(författare)
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Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden
- 2022
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Nature. - 0340-7004 .- 1432-0851. ; 71:8, s. 2029-2040
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-1 (Gal1) is a glycan-binding protein that promotes tumor progression by several distinct mechanisms. Through direct binding to vascular endothelial growth factor (VEGF)-receptor 2, Gal1 is able to induce VEGF-like signaling, which contributes to tumor angiogenesis. Furthermore, several studies have demonstrated an immunosuppressive function of Gal1 through effects on both effector and regulatory T cells. Elevated Gal1 expression and secretion have been shown in many tumor types, and high Gal1 serum levels have been connected to poor prognosis in cancer patients. These findings suggest that therapeutic strategies directed against Gal1 would enable simultaneous targeting of angiogenesis, immune evasion and metastasis. In the current study, we have analyzed the potential of Gal1 as a cancer vaccine target. We show that it is possible to generate high anti-Gal1 antibody levels in mice immunized with a recombinant vaccine protein consisting of bacterial sequences fused to Gal1. Growth of Gal1 expressing melanomas was significantly impaired in the immunized mice compared to the control group. This was associated with improved perfusion of the tumor vasculature, as well as increased infiltration of macrophages and cytotoxic T cells (CTLs). The level of granzyme B, mainly originating from CTLs in our model, was significantly elevated in Gal1 vaccinated mice and correlated with a decrease in tumor burden. We conclude that vaccination against Gal1 is a promising pro-immunogenic approach for cancer therapy that could potentially enhance the effect of other immunotherapeutic strategies due to its ability to promote CTL influx in tumors.
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| 5. |
- Saupe, Erin E., et al.
(författare)
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Climatic shifts drove major contractions in avian latitudinal distributions throughout the Cenozoic
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:26, s. 12895-12900
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Tidskriftsartikel (refereegranskat)abstract
- Many higher level avian clades are restricted to Earth's lower latitudes, leading to historical biogeographic reconstructions favoring a Gondwanan origin of crown birds and numerous deep subclades. However, several such tropical-restricted clades (TRCs) are represented by stem-lineage fossils well outside the ranges of their closest living relatives, often on northern continents. To assess the drivers of these geographic disjunctions, we combined ecological niche modeling, paleoclimate models, and the early Cenozoic fossil record to examine the influence of climatic change on avian geographic distributions over the last similar to 56 million years. By modeling the distribution of suitable habitable area through time, we illustrate that most Paleogene fossil-bearing localities would have been suitable for occupancy by extant TRC representatives when their stem-lineage fossils were deposited. Potentially suitable habitat for these TRCs is inferred to have become progressively restricted toward the tropics throughout the Cenozoic, culminating in relatively narrow circumtropical distributions in the present day. Our results are consistent with coarse-scale niche conservatism at the clade level and support a scenario whereby climate change over geological timescales has largely dictated the geographic distributions of many major avian clades. The distinctive modern bias toward high avian diversity at tropical latitudes for most hierarchical taxonomic levels may therefore represent a relatively recent phenomenon, overprinting a complex biogeographic history of dramatic geographic range shifts driven by Earth's changing climate, variable persistence, and intercontinental dispersal. Earth's current climatic trajectory portends a return to a megathermal state, which may dramatically influence the geographic distributions of many range-restricted extant clades.
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| 6. |
- Vogan, Aaron A., et al.
(författare)
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Combinations of Spok genes create multiple meiotic drivers in Podospora
- 2019
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Ingår i: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the Spok gene family underlies the Psks. The combination of Spok genes at different chromosomal locations defines the spore killer types and creates a killing hierarchy within a population. We identify two novel Spok homologs located within a large (74-167 kbp) region (the Spok block) that resides in different chromosomal locations in different strains. We confirm that the SPOK protein performs both killing and resistance functions and show that these activities are dependent on distinct domains, a predicted nuclease and kinase domain. Genomic and phylogenetic analyses across ascomycetes suggest that the Spok genes disperse through cross-species transfer, and evolve by duplication and diversification within lineages.
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| 7. |
- Clavé, Corinne, et al.
(författare)
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het-B allorecognition in Podospora anserina is determined by pseudo-allelic interaction of genes encoding a HET and lectin fold domain protein and a PII-like protein
- 2024
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Ingår i: PLOS Genetics. - 1553-7390 .- 1553-7404. ; 20:2
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Tidskriftsartikel (refereegranskat)abstract
- Filamentous fungi display allorecognition genes that trigger regulated cell death (RCD) when strains of unlike genotype fuse. Podospora anserina is one of several model species for the study of this allorecognition process termed heterokaryon or vegetative incompatibility. Incompatibility restricts transmission of mycoviruses between isolates. In P. anserina, genetic analyses have identified nine incompatibility loci, termed het loci. Here we set out to clone the genes controlling het-B incompatibility. het-B displays two incompatible alleles, het-B1 and het-B2. We find that the het-B locus encompasses two adjacent genes, Bh and Bp that exist as highly divergent allelic variants (Bh1/Bh2 and Bp1/Bp2) in the incompatible haplotypes. Bh encodes a protein with an N-terminal HET domain, a cell death inducing domain bearing homology to Toll/interleukin-1 receptor (TIR) domains and a C-terminal domain with a predicted lectin fold. The Bp product is homologous to PII-like proteins, a family of small trimeric proteins acting as sensors of adenine nucleotides in bacteria. We show that although the het-B system appears genetically allelic, incompatibility is in fact determined by the non-allelic Bh1/Bp2 interaction while the reciprocal Bh2/Bp1 interaction plays no role in incompatibility. The highly divergent C-terminal lectin fold domain of BH determines recognition specificity. Population studies and genome analyses indicate that het-B is under balancing selection with trans-species polymorphism, highlighting the evolutionary significance of the two incompatible haplotypes. In addition to emphasizing anew the central role of TIR-like HET domains in fungal RCD, this study identifies novel players in fungal allorecognition and completes the characterization of the entire het gene set in that species.
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| 8. |
- Daskalov, Asen, et al.
(författare)
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Contribution of specific residues of the β-solenoid fold to HET-s prion function, amyloid structure and stability.
- 2014
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- The [Het-s] prion of the fungus Podospora anserina represents a good model system for studying the structure-function relationship in amyloid proteins because a high resolution solid-state NMR structure of the amyloid prion form of the HET-s prion forming domain (PFD) is available. The HET-s PFD adopts a specific β-solenoid fold with two rungs of β-strands delimiting a triangular hydrophobic core. A C-terminal loop folds back onto the rigid core region and forms a more dynamic semi-hydrophobic pocket extending the hydrophobic core. Herein, an alanine scanning mutagenesis of the HET-s PFD was conducted. Different structural elements identified in the prion fold such as the triangular hydrophobic core, the salt bridges, the asparagines ladders and the C-terminal loop were altered and the effect of these mutations on prion function, fibril structure and stability was assayed. Prion activity and structure were found to be very robust; only a few key mutations were able to corrupt structure and function. While some mutations strongly destabilize the fold, many substitutions in fact increase stability of the fold. This increase in structural stability did not influence prion formation propensity in vivo. However, if an Ala replacement did alter the structure of the core or did influence the shape of the denaturation curve, the corresponding variant showed a decreased prion efficacy. It is also the finding that in addition to the structural elements of the rigid core region, the aromatic residues in the C-terminal semi-hydrophobic pocket are critical for prion propagation. Mutations in the latter region either positively or negatively affected prion formation. We thus identify a region that modulates prion formation although it is not part of the rigid cross-β core, an observation that might be relevant to other amyloid models.
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| 9. |
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| 10. |
- Martinossi-Allibert, Ivain, 1991-, et al.
(författare)
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To self or not to self? : Absence of mate choice despite costly outcrossing in the fungus Podospora anserina
- 2023
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Ingår i: Journal of Evolutionary Biology. - : John Wiley & Sons. - 1010-061X .- 1420-9101. ; 36:1, s. 238-250
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Tidskriftsartikel (refereegranskat)abstract
- Fungi have a large potential for flexibility in their mode of sexual reproduction, resulting in mating systems ranging from haploid selfing to outcrossing. However, we know little about which mating strategies are used in nature, and why, even in well-studied model organisms. Here, we explored the fitness consequences of alternative mating strategies in the ascomycete fungus Podospora anserina. We measured and compared fitness proxies of nine genotypes in either diploid selfing or outcrossing events, over two generations, and with or without environmental stress. We showed that fitness was consistently lower in outcrossing events, irrespective of the environment. The cost of outcrossing was partly attributed to non-self recognition genes with pleiotropic effects on fertility. We then predicted that when presented with options to either self or outcross, individuals would perform mate choice in favour of the reproductive strategy that yields higher fitness. Contrary to our prediction, individuals did not seem to avoid outcrossing when a choice was offered, in spite of the fitness cost incurred. Our results suggest that, although functionally diploid, P. anserina does not benefit from outcrossing in most cases. We outline different explanations for the apparent lack of mate choice in face of high fitness costs associated with outcrossing, including a new perspective on the pleiotropic effect of non-self recognition genes.
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| 11. |
- Saupe, Falk, et al.
(författare)
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Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously
- 2017
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Ingår i: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 31:3, s. 1204-1214
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Tidskriftsartikel (refereegranskat)abstract
- With the aim to improve the efficacy of therapeutic vaccines that target self-antigens, we have developed a novel fusion protein vaccine on the basis of the C-terminal multimerizing end of the variable lymphocyte receptor B (VLRB), the Ig equivalent in jawless fishes. Recombinant vaccines were produced in Escherichia coli by fusing the VLRB sequence to 4 different cancer-associated target molecules. The anti-self-immune response generated in mice that were vaccinated with VLRB vaccines was compared with the response in mice that received vaccines that contained bacterial thioredoxin (TRX), previously identified as an efficient carrier. The anti-self-Abswere analyzed with respect to titers, binding properties, and duration of response. VLRB-vaccinatedmice displayed a 2-to 10-fold increase in anti-self-Ab titers and a substantial decrease in Abs against the foreign part of the fusion protein compared with the response in TRX-vaccinated mice (P < 0.01). VLRB-generated Ab response had duration similar to the corresponding TRX-generatedAbs, but displayed a higher diversity in binding characteristics. Of importance, VLRB vaccines could sustain an immune response against several targets simultaneously. VLRB vaccines fulfill several key criteria for an efficient therapeutic vaccine that targets self-antigens as a result of its small size, its multimerizing capacity, and nonexposed foreign sequences in the fusion protein.- Saupe, F., Reichel, M., Huijbers, E. J. M., Femel, J., Markgren, P.- O., Andersson, C. E., Deindl, S., Danielson, U. H., Hellman, L. T., Olsson, A.- K. Development of a novel therapeutic vaccine carrier that sustains high antibody titers against several targets simultaneously.
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| 12. |
- Saupe, Falk, et al.
(författare)
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Vaccines targeting self-antigens : mechanisms and efficacy-determining parameters
- 2015
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 29:8, s. 3253-3262
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Tidskriftsartikel (refereegranskat)abstract
- We recently showed that it is possible to compromise tumor vessel function and, as a consequence, suppress growth of aggressive preclinical tumors by immunizing against the tumor vascular markers extra domain-A (ED-A) or -B (ED-B) of fibronectin, using a fusion protein consisting of the ED-A or ED-B peptide fused to bacterial thioredoxin. To address the mechanism behind fusion protein-induced immunization and the specific contribution of the different vaccine constituents to elicit an anti-self-antibody response, we immunized mice with modified or unmodified self-antigens, combined with different adjuvant components, and analyzed antibody responses by ELISA in sera. Several essential requirements to circumvent tolerance were identified: (1) a potent pattern recognition receptor agonist like an oligonucleotide containing unmethylated cytosine and guanine dinucleotides (CpG); (2) a depot adjuvant to keep the CpG at the site of injection; and (3) the presence of foreign sequences in the vaccine protein. Lack of either of these factors abolished the anti-self-response (P = 0.008). In mice genetically deficient for type I IFN signaling, there was a 60% reduction in the anti-self-response compared with wildtype (P = 0.011), demonstrating a key role of this pathway in CpG-induced circumvention of self-tolerance. Identification of these mechanistic requirements to generate a potent anti-self-immune response should significantly aid the design of efficient, specific, and safe therapeutic cancer vaccines.
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| 13. |
- Saupe, Sven J., et al.
(författare)
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On the Mechanistic Basis of Killer Meiotic Drive in Fungi
- 2022
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Ingår i: Annual Review of Microbiology. - : Punctum Books. - 0066-4227 .- 1545-3251. ; 76, s. 305-323
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Forskningsöversikt (refereegranskat)abstract
- Spore killers are specific genetic elements in fungi that kill sexual spores that do not contain them. A range of studies in the last few years have provided the long-awaited first insights into the molecular mechanistic aspects of spore killing in different fungal models, including both yeast-forming and filamentous Ascomycota. Here we describe these recent advances, focusing on the wtf system in the fission yeast Schizosaccharomyces pombe; the Sk spore killers of Neurospora species; and two spore-killer systems in Podospora anserina, Spok and [Het-s]. The spore killers appear thus far mechanistically unrelated. They can involve large genomic rearrangements but most often rely on the action of just a single gene. Data gathered so far show that the protein domains involved in the killing and resistance processes differ among the systems and are not homologous. The emerging picture sketched by these studies is thus one of great mechanistic and evolutionary diversity of elements that cheat during meiosis and are thereby preferentially inherited over sexual generations.
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| 14. |
- Tribouillard-Tanvier, Deborah, et al.
(författare)
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Protein Folding Activity of Ribosomal RNA Is a Selective Target of Two Unrelated Antiprion Drugs
- 2008
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 3:5, s. e2174-
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Tidskriftsartikel (refereegranskat)abstract
- Background: 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases. Methodology/Principal Findings: Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome. Conclusion/Significance: 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity.
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| 15. |
- Vogan, Aaron A., et al.
(författare)
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The Enterprise, a massive transposon carrying Spok meiotic drive genes
- 2021
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory Press (CSHL). - 1088-9051 .- 1549-5469. ; 31:5, s. 789-798
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Tidskriftsartikel (refereegranskat)abstract
- The genomes of eukaryotes are full of parasitic sequences known as transposable elements (TEs). Most TEs studied to date are relatively small (50 — 12000 bp), but can contribute to very large proportions of genomes. Here we report the discovery of a giant tyrosine-recombinase-mobilized DNA transposon, Enterprise, from the model fungus Podospora anserina. Previously, we described a large genomic feature called the Spok block which is notable due to the presence of meiotic drive genes of the Spok gene family. The Spok block ranges from 110 kb to 247 kb and can be present in at least four different genomic locations within P. anserina, despite what is an otherwise highly conserved genome structure. We have determined that the reason for its varying positions is that the Spok block is not only capable of meiotic drive, but is also capable of transposition. More precisely, the Spok block represents a unique case where the Enterprise has captured the Spoks, thereby parasitizing a resident genomic parasite to become a genomic hyperparasite. Furthermore, we demonstrate that Enterprise (without the Spoks) is found in other fungal lineages, where it can be as large as 70 kb. Lastly, we provide experimental evidence that the Spok block is deleterious, with detrimental effects on spore production in strains which carry it. In contrast to the selfish role of the Enterprise in P. anserina, we speculate that the mobility of the Enterprise may also play an adaptive role in many other fungi, through the horizontal transfer of metabolic genes. This union of meiotic drivers and a transposon has created a selfish element of impressive size in Podospora, challenging our perception of how TEs influence genome evolution and broadening the horizons in terms of what the upper limit of transposition may be.
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