Genetic variation plays a fundamental role in driving evolutionary adaptations and innovations. Traditionally, genetic variation has been primarily assessed through single nucleotide differences among individuals. However, it is becoming increasingly clear that variations in the structure and organization of genomes also contribute significantly to genetic diversity. Understanding the impact of this “structural” variation on evolution is still in its early stages, but it is believed to have unique implications for the development and maintenance of adaptive traits. Structural mutations, such as insertions, deletions, inversions, rearrangements, and mobile element activity, can result in substantial changes in DNA sequences, affect inheritance patterns, and influence genomic stability. Therefore, identifying the mechanisms that generate selectable variation in genome structure and unraveling their phenotypic consequences are vital for unraveling the genetic basis of adaptation.
During my Ph.D., I focused on studying the evolution of fungicide resistance in fungal pathogens, which poses a significant threat to the health of animals and plants. The rapid emergence of pathogens with reduced sensitivity to specific fungicides demonstrates the dynamic process of resistance evolution. In the context of European agricultural fields, where target-site fungicides have been extensively used for the past three decades, it offers an excellent opportunity to investigate the spatial and temporal patterns of specific resistance mutations. One such class of fungicides is demethylation inhibitors (DMIs) that target the CYP51 enzyme involved in essential cellular processes. Structural changes in the target protein are the most common mechanism leading to insensitivity to DMIs. However, evidence suggests that additional genetic loci also contribute to overall resistance. In my research, I aimed to uncover the evolutionary trajectories driving the genetic architecture of fungicide resistance in the major wheat pathogen, Zymoseptoria tritici, specifically against five widely used DMIs. Utilizing a comprehensive collection of 1420 whole-genome sequenced isolates from 27 European countries over a 15-year period, I employed genome-wide association mapping techniques, incorporating multiple phenotyping and genotyping methods, to identify previously unknown loci associated with DMI resistance. This analysis revealed extensive genetic diversity and divergence in the genetic architecture of resistance, even though the DMIs target the same protein. The findings from this study emphasize the power of microbial genome-wide association studies in elucidating the rapid evolutionary processes underlying fungicide resistance.
Overall, by investigating the structural variations in genomes and their implications for adaptation, my research sheds light on the mechanisms driving genetic diversity and resistance evolution. Understanding these processes is crucial for the development of effective strategies to mitigate the emergence and spread of fungicide resistance in fungal pathogens, contributing to the long-term sustainability of agricultural practices and ecosystem health.