Supporting data for: "Giant transposons promote strain heterogeneity in a major fungal pathogen"

Fungal infections are difficult to prevent and treat in large part due to heterogeneity in clinically relevant phenotypes. However, the genetic mechanisms driving pathogen variation remain poorly understood. Here, we determined the extent to which <i>Starships</i>—giant transposons capable of mobilizing numerous fungal genes—generate genetic and phenotypic variability in the human pathogen <i>Aspergillus fumigatus</i>. We analyzed 519 diverse strains, including 12 newly sequenced with long-read technology, to reveal 20 distinct <i>Starships </i>that generate genomic heterogeneity over timescales impacting experimental reproducibility. <i>Starship</i>-mobilized genes encode diverse functions, including biofilm-related virulence factors and biosynthetic gene clusters, and many are differentially expressed during infection and antifungal exposure in a strain-specific manner. These findings support a new model of fungal pathogenesis wherein <i>Starships </i>mediate variation in virulence-related gene content and expression. Together, our results demonstrate that <i>Starships </i>are a foundational mechanism generating disease-relevant genotypic and, in turn, phenotypic heterogeneity in a major human fungal pathogen.

真菌感染的防控与治疗始终颇具挑战，这在很大程度上源于其临床相关表型的异质性。然而，驱动病原体变异的遗传机制仍有待深入阐明。本研究针对人类致病真菌烟曲霉（*Aspergillus fumigatus*），探究一类可移动大量真菌基因的巨型转座子——星型转座子（Starships）介导遗传与表型变异的程度。我们对519株遗传多样性丰富的菌株开展分析，其中包含12株采用长读长测序技术新完成测序的菌株，最终鉴定出20种不同的星型转座子，它们可在影响实验重复性的时间尺度上引发基因组异质性。经星型转座子移动的基因编码多样功能，包括与生物膜相关的毒力因子以及生物合成基因簇，其中多数基因在感染过程及抗真菌药物暴露时，会以菌株特异性的方式呈现差异表达。上述研究结果支持一种全新的真菌致病模型，即星型转座子可介导毒力相关基因的含量与表达模式变异。综上，本研究结果证实，星型转座子是一类核心遗传机制，可在主要人类致病真菌中引发与疾病相关的基因型变异，并进而导致表型异质性。