ORCID Profile
0000-0002-2146-5507
Current Organisation
Australian National University
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Publisher: Oxford University Press (OUP)
Date: 16-03-2021
DOI: 10.1093/G3JOURNAL/JKAB068
Abstract: Transposable elements (TEs) impact genome plasticity, architecture, and evolution in fungal plant pathogens. The wide range of TE content observed in fungal genomes reflects erse efficacy of host-genome defense mechanisms that can counter-balance TE expansion and spread. Closely related species can harbor drastically different TE repertoires. The evolution of fungal effectors, which are crucial determinants of pathogenicity, has been linked to the activity of TEs in pathogen genomes. Here, we describe how TEs have shaped genome evolution of the fungal wheat pathogen Zymoseptoria tritici and four closely related species. We compared de novo TE annotations and repeat-induced point mutation signatures in 26 genomes from the Zymoseptoria species-complex. Then, we assessed the relative insertion ages of TEs using a comparative genomics approach. Finally, we explored the impact of TE insertions on genome architecture and plasticity. The 26 genomes of Zymoseptoria species reflect different TE dynamics with a majority of recent insertions. TEs associate with accessory genome compartments, with chromosomal rearrangements, with gene presence/absence variation, and with effectors in all Zymoseptoria species. We find that the extent of RIP-like signatures varies among Z. tritici genomes compared to genomes of the sister species. The detection of a reduction of RIP-like signatures and TE recent insertions in Z. tritici reflects ongoing but still moderate TE mobility.
Publisher: Cold Spring Harbor Laboratory
Date: 29-03-2020
DOI: 10.1101/2020.03.27.012203
Abstract: DNA methylation is found throughout all domains of life, yet the extent and function of DNA methylation differ between eukaryotes. Strains of the plant pathogenic fungus Zymoseptoria tritici appeared to lack cytosine DNA methylation (5mC) because gene lification followed by Repeat-Induced Point mutation (RIP) resulted in the inactivation of the dim2 DNA methyltransferase gene. 5mC is, however, present in closely related sister species. We demonstrate that inactivation of dim2 occurred recently as some Z. tritici isolates carry a functional dim2 gene. Moreover, we show that dim2 inactivation occurred by a different path than previously hypothesized. We mapped the genome-wide distribution of 5mC in strains with and without functional dim2 . Presence of functional dim2 correlates with high levels of 5mC in transposable elements (TEs), suggesting a role in genome defense. We identified low levels of 5mC in strains carrying inactive dim2 alleles, suggesting that 5mC is maintained over time, presumably by an active Dnmt5 DNA methyltransferase. Integration of a functional dim2 allele in strains with mutated dim2 restored normal 5mC levels, demonstrating de novo cytosine methylation activity of dim2 . To assess the importance of 5mC for genome evolution, we performed an evolution experiment, comparing genomes of strains with high levels of 5mC to genomes of strains lacking dim2 . We found that the presence of dim2 alters nucleotide composition by promoting C to T transitions (C→T) specifically at CpA (CA) sites during mitosis, likely contributing to TE inactivation. Our results show that 5mC density at TEs is a polymorphic trait in Z. tritici populations that can impact genome evolution. Cytosine DNA methylation (5mC) is known to silence transposable elements in fungi and thereby appears to contribute to genome stability. The genomes of plant pathogenic fungi are highly erse, differing substantially in transposon content and distribution. Here, we show extensive differences of 5mC levels within a single species of an important wheat pathogen. These differences were caused by inactivation of the DNA methyltransferase Dim2 in the majority of studied isolates. Presence of widespread 5mC increased point mutation rates in regions with active or mutated transposable elements during mitosis. The mutation pattern is dependent on the presence of Dim2 and resembles a mitotic version of Repeat-Induced Point mutation (RIP). Thus, loss of 5mC may represent an evolutionary trade-off offering adaptive potential at the cost of transposon control.
Publisher: Cold Spring Harbor Laboratory
Date: 26-10-2018
DOI: 10.1101/454223
Abstract: Chromosome and genome stability are important for normal cell function as instability often correlates with disease and dysfunction of DNA repair mechanisms. Many organisms maintain supernumerary or accessory chromosomes that deviate from standard chromosomes. The pathogenic fungus Zymoseptoria tritici has as many as eight accessory chromosomes, which are highly unstable during meiosis and mitosis, transcriptionally repressed, show enrichment of repetitive elements, and enrichment with heterochromatic histone methylation marks, e.g., trimethylation of H3 lysine 9 or lysine 27 (H3K9me3, H3K27me3). To elucidate the role of heterochromatin on genome stability in Z. tritici, we deleted the genes encoding the methyltransferases responsible for H3K9me3 and H3K27me3, kmt1 and kmt6 , respectively, and generated a double mutant. We combined experimental evolution and genomic analyses to determine the impact of these deletions on chromosome and genome stability, both in vitro and in planta . We used whole genome sequencing, ChIP-seq, and RNA-seq to compare changes in genome and chromatin structure, and differences in gene expression between mutant and wildtype strains. Analyses of genome and ChIP-seq data in H3K9me3-deficient strains revealed dramatic chromatin reorganization, where H3K27me3 is mostly relocalized into regions that are enriched with H3K9me3 in wild type. Many genome rearrangements and formation of new chromosomes were found in the absence of H3K9me3, accompanied by activation of transposable elements. In stark contrast, loss of H3K27me3 actually increased the stability of accessory chromosomes under normal growth conditions in vitro , even without large scale changes in gene activity. We conclude that H3K9me3 is important for the maintenance of genome stability because it disallows H3K27me3 in these regions. In this system, H3K27me3 reduces the overall stability of accessory chromosomes, generating a “metastable” state for these quasi-essential regions of the genome. Genome and chromosome stability are essential to maintain normal cell function and viability. However, differences in genome and chromosome structure are frequently found in organisms that undergo rapid adaptation to changing environmental conditions, and in humans are often found in cancer cells. We study genome instability in a fungal pathogen that exhibits a high degree of genetic ersity. Regions that show extraordinary ersity in this pathogen are the transposon-rich accessory chromosomes, which contain few genes that are of unknown benefit to the organism but maintained in the population and thus considered “quasi essential”. Accessory chromosomes in all fungi studied so far are enriched with markers for heterochromatin, namely trimethylation of H3 lysine 9 and 27 (H3K9me3, H3K27me3). We show that loss of these heterochromatin marks has strong but opposing effects on genome stability. While loss of the transposon-associated mark H3K9me3 destabilizes the entire genome, presence of H3K27me3 favors instability of accessory chromosomes. Our study provides insight into the relationship between chromatin and genome stability and why some regions are more susceptible to genetic ersity than others.
Publisher: Springer Science and Business Media LLC
Date: 07-08-2017
Abstract: The fungal kingdom comprises some of the most devastating plant pathogens. Sequencing the genomes of fungal pathogens has shown a remarkable variability in genome size and architecture. Population genomic data enable us to understand the mechanisms and the history of changes in genome size and adaptive evolution in plant pathogens. Although transposable elements predominantly have negative effects on their host, fungal pathogens provide prominent ex les of advantageous associations between rapidly evolving transposable elements and virulence genes that cause variation in virulence phenotypes. By providing homogeneous environments at large regional scales, managed ecosystems, such as modern agriculture, can be conducive for the rapid evolution and dispersal of pathogens. In this Review, we summarize key ex les from fungal plant pathogen genomics and discuss evolutionary processes in pathogenic fungi in the context of molecular evolution, population genomics and agriculture.
Publisher: Elsevier BV
Date: 06-2015
Publisher: Public Library of Science (PLoS)
Date: 22-03-2021
DOI: 10.1371/JOURNAL.PGEN.1009448
Abstract: DNA methylation is found throughout all domains of life, yet the extent and function of DNA methylation differ among eukaryotes. Strains of the plant pathogenic fungus Zymoseptoria tritici appeared to lack cytosine DNA methylation (5mC) because gene lification followed by Repeat-Induced Point mutation (RIP) resulted in the inactivation of the dim2 DNA methyltransferase gene. 5mC is, however, present in closely related sister species. We demonstrate that inactivation of dim2 occurred recently as some Z . tritici isolates carry a functional dim2 gene. Moreover, we show that dim2 inactivation occurred by a different path than previously hypothesized. We mapped the genome-wide distribution of 5mC in strains with or without functional dim2 alleles. Presence of functional dim2 correlates with high levels of 5mC in transposable elements (TEs), suggesting a role in genome defense. We identified low levels of 5mC in strains carrying non-functional dim2 alleles, suggesting that 5mC is maintained over time, presumably by an active Dnmt5 DNA methyltransferase. Integration of a functional dim2 allele in strains with mutated dim2 restored normal 5mC levels, demonstrating de novo cytosine methylation activity of Dim2. To assess the importance of 5mC for genome evolution, we performed an evolution experiment, comparing genomes of strains with high levels of 5mC to genomes of strains lacking functional dim2 . We found that presence of a functional dim2 allele alters nucleotide composition by promoting C to T transitions (C→T) specifically at CpA (CA) sites during mitosis, likely contributing to TE inactivation. Our results show that 5mC density at TEs is a polymorphic trait in Z . tritici populations that can impact genome evolution.
Publisher: Wiley
Date: 26-12-2018
DOI: 10.1002/ECE3.4724
Publisher: Cold Spring Harbor Laboratory
Date: 26-11-2022
DOI: 10.1101/2022.11.25.517763
Abstract: Facultative heterochromatin controls development and differentiation in many eukaryotes. In metazoans, plants, and many filamentous fungi, facultative heterochromatin is characterized by transcriptional repression and enrichment with nucleosomes that are trimethylated at histone H3 lysine 27 (H3K27me3). While loss of H3K27me3 results in derepression of transcriptional gene silencing in many species, additional up- and downstream layers of regulation are necessary to mediate control of transcription in chromosome regions enriched with H3K27me3. Here, we investigated the effects of one histone mark on histone H4, namely H4K20me3, in the fungus Zymoseptoria tritici , a globally important pathogen of wheat. Deletion of kmt5 , the gene encoding the sole methyltransferase responsible for H4K20 methylation, resulted in global derepression of transcription, especially in regions of facultative heterochromatin. Reversal of silencing in the absence of H4K20me3 not only affected genes but also a large number of novel, previously undetected, non-coding transcripts generated from regions of facultative heterochromatin on accessory chromosomes. Transcriptional activation in kmt5 deletion strains was accompanied by a complete loss of Ash1-mediated H3K36me3 and chromatin reorganization affecting H3K27me3 and H3K4me2 distribution in regions of facultative heterochromatin. Strains with a H4K20M mutation in the single histone H4 gene of Z. tritici recapitulated these chromatin changes, suggesting that H4K20me3 is essential for Ash1-mediated H3K36me3. The Δ kmt5 mutants we obtained are more sensitive to genotoxic stressors and both, Δ kmt5 and Δ ash1 , showed greatly increased rates of accessory chromosome loss. Taken together, our results provide insights into a novel, and unsuspected, mechanism controlling the assembly and maintenance of facultative heterochromatin. Facultative heterochromatin contains genes important for specific developmental or life cycle stages. Transcriptional regulation of these genes is influenced by chromatin structure. Here, we report that a little studied histone modification, trimethylation of lysine 20 on histone H4 (H4K20me3), is enriched in facultative heterochromatin and important for transcriptional repression in these regions in an important agricultural pathogen. Furthermore, normal levels of H4K20me3 are essential for deposition of another repressive histone mark, Ash1-mediated H3K36me3, and affect the distribution of other marks including H3K27me3. We conducted the first genome-wide assessment of H4K20 methylation levels in a fungus, and our discoveries reveal that multiple chromatin modifications are required to establish transcriptional silencing, providing the framework to understand epistasis relationships among these histone marks.
Publisher: Springer Science and Business Media LLC
Date: 26-08-2020
DOI: 10.1186/S12864-020-06871-W
Abstract: Antagonistic co-evolution can drive rapid adaptation in pathogens and shape genome architecture. Comparative genome analyses of several fungal pathogens revealed highly variable genomes, for many species characterized by specific repeat-rich genome compartments with exceptionally high sequence variability. Dynamic genome structure may enable fast adaptation to host genetics. The wheat pathogen Zymoseptoria tritici with its highly variable genome, has emerged as a model organism to study genome evolution of plant pathogens. Here, we compared genomes of Z. tritici isolates and of sister species infecting wild grasses to address the evolution of genome composition and structure. Using long-read technology, we sequenced and assembled genomes of Z. ardabiliae , Z. brevis , Z. pseudotritici and Z. passerinii , together with two isolates of Z. tritici . We report a high extent of genome collinearity among Zymoseptoria species and high conservation of genomic, transcriptomic and epigenomic signatures of compartmentalization. We identify high gene content variability both within and between species. In addition, such variability is mainly limited to the accessory chromosomes and accessory compartments. Despite strong host specificity and non-overlapping host-range between species, predicted effectors are mainly shared among Zymoseptoria species, yet exhibiting a high level of presence-absence polymorphism within Z. tritici . Using in planta transcriptomic data from Z. tritici , we suggest different roles for the shared orthologs and for the accessory genes during infection of their hosts. Despite previous reports of high genomic plasticity in Z. tritici , we describe here a high level of conservation in genomic, epigenomic and transcriptomic composition and structure across the genus Zymoseptoria . The compartmentalized genome allows the maintenance of a functional core genome co-occurring with a highly variable accessory genome.
Publisher: MDPI AG
Date: 09-06-2020
Abstract: Genome integrity is essential to maintain cellular function and viability. Consequently, genome instability is frequently associated with dysfunction in cells and associated with plant, animal, and human diseases. One consequence of relaxed genome maintenance that may be less appreciated is an increased potential for rapid adaptation to changing environments in all organisms. Here, we discuss evidence for the control and function of facultative heterochromatin, which is delineated by methylation of histone H3 lysine 27 (H3K27me) in many fungi. Aside from its relatively well understood role in transcriptional repression, accumulating evidence suggests that H3K27 methylation has an important role in controlling the balance between maintenance and generation of novelty in fungal genomes. We present a working model for a minimal repressive network mediated by H3K27 methylation in fungi and outline challenges for future research.
Publisher: Public Library of Science (PLoS)
Date: 22-04-2019
Publisher: Oxford University Press (OUP)
Date: 02-08-2018
DOI: 10.1534/GENETICS.118.301050
Abstract: The ability to rapidly adapt to changing environments is crucial for the success of pathogens infecting plants and animals. In some eukaryotic pathogens, rapid evolution can be mediated by genome rearrangements, which... The haploid genome of the pathogenic fungus Zymoseptoria tritici is contained on “core” and “accessory” chromosomes. While 13 core chromosomes are found in all strains, as many as eight accessory chromosomes show presence/absence variation and rearrangements among field isolates. The factors influencing these presence/absence polymorphisms are so far unknown. We investigated chromosome stability using experimental evolution, karyotyping, and genome sequencing. We report extremely high and variable rates of accessory chromosome loss during mitotic propagation in vitro and in planta. Spontaneous chromosome loss was observed in 2 to & % of cells during 4 weeks of incubation. Similar rates of chromosome loss in the closely related Zymoseptoria ardabiliae suggest that this extreme chromosome dynamic is a conserved phenomenon in the genus. Elevating the incubation temperature greatly increases instability of accessory and even core chromosomes, causing severe rearrangements involving telomere fusion and chromosome breakage. Chromosome losses do not affect the fitness of Zymoseptoria tritici in vitro, but some lead to increased virulence, suggesting an adaptive role of this extraordinary chromosome instability.
Publisher: Public Library of Science (PLoS)
Date: 25-09-2023
Start Date: 2019
End Date: 2021
Funder: Deutsche Forschungsgemeinschaft
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