Biology subjects

Fouche, S.

Publications and source records attributed to Fouche, S..

5 recordsLinked to original sources

bioRxiv2023

Recurrent chromosome destabilization through repeat-mediated rearrangements in a fungal pathogen

Genomic instability caused by chromosomal rearrangements has severe consequences for organismal fitness and progression of cancerous cell lines. The triggers of destabilized chromosomes remain poorly understood but likely co-locate with fragile sites. Here, we retrace a runaway chromosomal degeneration process observed in a fungal pathogen using telomere-to-telomere assemblies across an experimental progeny. We show that the same fragile sites triggered reproducible, large-scale rearrangements through non-allelic recombination. Across our four-generation progeny, chromosomal rearrangements were accompanied by non-disjunction events leading to aneuploid progeny with up to four chromosomal copies. We identify a specific transposable element family co-locating with fragile sites, likely triggering ongoing repeated chromosomal degeneration. The element has recently been associated with lower virulence of the pathogen and has undergone an expansion of copy numbers across the genome. Chromosome sequences are also targeted by repeat-induced point mutation, a genome defense mechanism actively leading to hypermutation on duplicated sequences. Our work identifies the exact sequence triggers that initiate chromosome instability and perpetuate degenerative cycles. Dissecting proximate causes leading to runaway chromosomal degeneration could expand our understanding of chromosomal evolution beyond fungal pathogens.

genomics↗

bioRxiv2020

Machine-learning predicts genomic determinants of meiosis-driven structural variation in a eukaryotic pathogen

Species harbor extensive structural variation underpinning recent adaptive evolution and major disease phenotypes. Most sequence rearrangements are generated non-randomly along the genome through non-allelic recombination and transposable element activity. However, the causality between genomic features and the induction of new rearrangements is poorly established. Here, we analyze a global set of telomere-to-telomere genome assemblies of a major fungal pathogen of wheat to establish a nucleotide-level map of structural variation. We show that the recent emergence of pesticide resistance has been disproportionally driven by rearrangements. We used machine-learning to train a model on structural variation events based on 30 chromosomal sequence features. We show that base composition and gene density are the major determinants of structural variation. Low-copy LINE and Gypsy retrotransposons explain most inversion, indel and duplication events. We retrain our model on Arabidopsis thaliana and show that our modelling approach can be extended to more complex genomes. Finally, we analyzed complete genomes of haploid offspring in a four-generation pedigree. Meiotic crossover locations were enriched for newly generated structural variation consistent with crossovers being mutational hotspots. The model trained on species-wide structural variation predicted the position of >74% of the newly generated variants along the pedigree. The predictive power highlights causality between specific sequence features and the induction of chromosomal rearrangements. Our work demonstrates that training sequence-derived models can accurately identify regions of intrinsic DNA instability in eukaryotic genomes.

genomics↗

bioRxiv2019

Stress-driven transposable element de-repression dynamics in a fungal pathogen

Transposable elements (TEs) are drivers of genome evolution and affect the expression landscape of the host genome. Stress is a major factor inducing TE activity, however the regulatory mechanisms underlying de-repression are poorly understood. Key unresolved questions are whether different types of stress differentially induce TE activity and whether different TEs respond differently to the same stress. Plant pathogens are excellent models to dissect the impact of stress on TEs, because lifestyle transitions on and off the host impose exposure to a variety of stress conditions. We analyzed the TE expression landscape of four well-characterized strains of the major wheat pathogen Zymoseptoria tritici. We experimentally exposed strains to nutrient starvation and host infection stress. Contrary to expectations, we show that the two distinct conditions induce the expression of different sets of TEs. In particular, the most highly expressed TEs, including MITE and LTR-Gypsy elements, show highly distinct de-repression across stress conditions. Both the genomic context of TEs and the genetic background stress (i.e. different strains harboring the same TEs) were major predictors of de-repression dynamics under stress. Genomic defenses inducing point mutations in repetitive regions were largely ineffective to prevent TE de-repression. Consistent with TE de-repression being governed by epigenetic effects, we found that gene expression profiles under stress varied significantly depending on the proximity to the closest TEs. The unexpected complexity in TE responsiveness to stress across genetic backgrounds and genomic locations shows that species harbor substantial genetic variation to control TEs.

genomics↗

bioRxiv2018

Precision phenotyping reveals novel loci for quantitative resistance to septoria tritici blotch in European winter wheat

O_LIAccurate, high-throughput phenotyping for quantitative traits is the limiting factor for progress in plant breeding. We developed automated image analysis to measure quantitative resistance to septoria tritici blotch (STB), a globally important wheat disease, enabling identification of small chromosome intervals containing plausible candidate genes for STB resistance.\nC_LIO_LI335 winter wheat cultivars were included in a replicated field experiment that experienced natural epidemic development by a highly diverse but fungicide-resistant pathogen population. More than 5.4 million automatically generated phenotypes were associated with 13,648 SNP markers to perform a GWAS.\nC_LIO_LIWe identified 26 chromosome intervals explaining 1.9-10.6% of the variance associated with four resistance traits. Seventeen of the intervals were less than 5 Mbp in size and encoded only 173 genes, including many genes associated with disease resistance. Five intervals contained four or fewer genes, providing high priority targets for functional validation. Ten chromosome intervals were not previously associated with STB resistance.\nC_LIO_LIOur experiment illustrates how high-throughput automated phenotyping can accelerate breeding for quantitative disease resistance. The SNP markers associated with these chromosome intervals can be used to recombine different forms of quantitative STB resistance that are likely to be more durable than pyramids of major resistance genes.\nC_LI

plant biology↗

bioRxiv2017

Meiosis leads to pervasive segregation distortion and copy-number variation in accessory chromosomes of the wheat pathogen Zymoseptoria tritici

Meiosis is one of the most conserved molecular processes in eukaryotes. The fidelity of pairing and segregation of homologous chromosomes has a major impact on the proper transmission of genetic information. Aberrant chromosomal transmission can have major phenotypic consequences, yet the mechanisms are poorly understood. Fungi are excellent models to investigate processes of chromosomal transmission, because many species have highly polymorphic genomes that include accessory chromosomes. Inheritance of accessory chromosomes is often unstable and chromosomal losses have little impact on fitness. We analyzed chromosomal inheritance in 477 progeny coming from two crosses of the fungal wheat pathogen Zymoseptoria tritici. For this, we developed a high-throughput screening method based on restriction site associated DNA sequencing (RAD-seq) that generated dense coverage of genetic markers along each chromosome. We identified rare instances of chromosomal duplications (disomy) in core chromosomes. Accessory chromosomes showed high overall frequencies of disomy. Chromosomal rearrangements were found exclusively on accessory chromosomes and were more frequent than disomy. Accessory chromosomes present in only one of the parents in an analyzed cross were inherited at significantly higher rates than the expected 1:1 segregation ratio. Both the chromosome and the parental background had significant impacts on the rates of disomy, losses, rearrangements and segregation distortion. We found that chromosomes with higher sequence similarity and lower repeat content were inherited more faithfully. The large number of rearranged progeny chromosomes identified in this species will enable detailed analyses of the mechanisms underlying chromosomal rearrangement.

evolutionary biology↗