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1. Giant transposons promote strain heterogeneity in a major fungal pathogen

   https://doi.org/10.1128/mbio.01092-25  

   Gluck-Thaler, Emile; Forsythe, Adrian; Puerner, Charles; Gutierrez-Perez, Cecilia; Stajich, Jason E; Croll, Daniel; Cramer, Robert A; Vogan, Aaron A (June 2025, mBio)

   Goldman, Gustavo H (Ed.)

   ABSTRACT Fungal infections are difficult to prevent and treat in large part due to strain heterogeneity, which confounds diagnostic predictability. Yet, the genetic mechanisms driving strain-to-strain variation remain poorly understood. Here, we determined the extent to whichStarships—giant transposons capable of mobilizing numerous fungal genes—generate genetic and phenotypic variability in the opportunistic human pathogenAspergillus fumigatus. We analyzed 519 diverse strains, including 11 newly sequenced with long-read technology and multiple isolates of the same reference strain, to reveal 20 distinctStarshipsthat are generating genomic heterogeneity over timescales relevant for experimental reproducibility.Starship-mobilized genes encode diverse functions, including known 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 evolution whereinStarshipshelp generate variation in genome structure, gene content, and expression among fungal strains. Together, our results demonstrate thatStarshipsare a previously hidden mechanism generating genotypic and, in turn, phenotypic heterogeneity in a major human fungal pathogen.IMPORTANCENo “one size fits all” option exists for treating fungal infections in large part due to genetic and phenotypic variability among strains. Accounting for strain heterogeneity is thus fundamental for developing efficacious treatments and strategies for safeguarding human health. Here, we report significant progress toward achieving this goal by uncovering a previously hidden mechanism generating heterogeneity in the human fungal pathogenAspergillus fumigatus: giant transposons, calledStarships, that span dozens of kilobases and mobilize fungal genes as cargo. By conducting a systematic investigation of these unusual transposons in a single fungal species, we demonstrate their contributions to population-level variation at the genome, pangenome, and transcriptome levels. TheStarshipcompendium we develop will not only help predict variation introduced by these elements in laboratory experiments but will serve as a foundational resource for determining howStarshipsimpact clinically relevant phenotypes, such as antifungal resistance and pathogenicity. 

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2. Draft genome sequences for Neonectria magnoliae and Neonectria punicea, canker pathogens of Liriodendron tulipifera and Acer saccharum in West Virginia

   https://doi.org/10.1128/mra.01042-24  

   Petronek, Hannah M; Kasson, Matt T; Metheny, Amy M; Stauder, Cameron M; Lovett, Brian; Lynch, Shannon C; Garnas, Jeff R; Kasson, Lindsay R; Stajich, Jason E (November 2024, Microbiology Resource Announcements)

   Hudson, André O (Ed.)

   ABSTRACT The fungal genusNeonectriacontains many phytopathogenic species currently impacting forests and fruit trees worldwide. Despite their importance, a majority ofNeonectriaspp. lack sufficient genomic resources to resolve suspected cryptic species. Here, we report draft genomes and assemblies forNeonectria magnoliaeNRRL 64651 andNeonectria puniceaNRRL 64653. 

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3. The pan-genome of Aspergillus fumigatus provides a high-resolution view of its population structure revealing high levels of lineage-specific diversity driven by recombination

   https://doi.org/10.1371/journal.pbio.3001890  

   Lofgren, Lotus A.; Ross, Brandon S.; Cramer, Robert A.; Stajich, Jason E. (November 2022, PLOS Biology)

   Sil, Anita (Ed.)

   Aspergillus fumigatus is a deadly agent of human fungal disease where virulence heterogeneity is thought to be at least partially structured by genetic variation between strains. While population genomic analyses based on reference genome alignments offer valuable insights into how gene variants are distributed across populations, these approaches fail to capture intraspecific variation in genes absent from the reference genome. Pan-genomic analyses based on de novo assemblies offer a promising alternative to reference-based genomics with the potential to address the full genetic repertoire of a species. Here, we evaluate 260 genome sequences of A . fumigatus including 62 newly sequenced strains, using a combination of population genomics, phylogenomics, and pan-genomics. Our results offer a high-resolution assessment of population structure and recombination frequency, phylogenetically structured gene presence–absence variation, evidence for metabolic specificity, and the distribution of putative antifungal resistance genes. Although A . fumigatus disperses primarily via asexual conidia, we identified extraordinarily high levels of recombination with the lowest linkage disequilibrium decay value reported for any fungal species to date. We provide evidence for 3 primary populations of A . fumigatus , with recombination occurring only rarely between populations and often within them. These 3 populations are structured by both gene variation and distinct patterns of gene presence–absence with unique suites of accessory genes present exclusively in each clade. Accessory genes displayed functional enrichment for nitrogen and carbohydrate metabolism suggesting that populations may be stratified by environmental niche specialization. Similarly, the distribution of antifungal resistance genes and resistance alleles were often structured by phylogeny. Altogether, the pan-genome of A . fumigatus represents one of the largest fungal pan-genomes reported to date including many genes unrepresented in the Af293 reference genome. These results highlight the inadequacy of relying on a single-reference genome-based approach for evaluating intraspecific variation and the power of combined genomic approaches to elucidate population structure, genetic diversity, and putative ecological drivers of clinically relevant fungi. 

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4. Plastid phylogenomics uncovers multiple species in Medicago truncatula (Fabaceae) germplasm accessions

   https://doi.org/10.1038/s41598-022-25381-1  

   Choi, In-Su; Wojciechowski, Martin F.; Steele, Kelly P.; Hopkins, Andrew; Ruhlman, Tracey A.; Jansen, Robert K. (December 2022, Scientific Reports)

   N/A (Ed.)

   Abstract Medicago truncatulais a model legume that has been extensively investigated in diverse subdisciplines of plant science.Medicago littoraliscan interbreed withM. truncatulaandM. italica; these three closely related species form a clade, i.e. TLI clade. Genetic studies have indicated thatM. truncatulaaccessions are heterogeneous but their taxonomic identities have not been verified. To elucidate the phylogenetic position of diverseM. truncatulaaccessions within the genus, we assembled 54 plastid genomes (plastomes) using publicly available next-generation sequencing data and conducted phylogenetic analyses using maximum likelihood. Five accessions showed high levels of plastid DNA polymorphism. Three of these highly polymorphic accessions contained sequences from bothM. truncatulaandM. littoralis.Phylogenetic analyses of sequences placed some accessions closer to distantly related species suggesting misidentification of source material.Most accessions were placed within the TLI clade and maximally supported the interrelationships of three subclades. TwoMedicagoaccessions were placed within aM. italicasubclade of the TLI clade. Plastomes with a 45-kb (rpl20-ycf1) inversion were placed within theM. littoralissubclade. Our results suggest that theM. truncatulaaccession genome pool represents more than one species due to possible mistaken identities and gene flow among closely related species. 

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5. Mitochondrial genome diversity across the subphylum Saccharomycotina

   https://doi.org/10.3389/fmicb.2023.1268944  

   Wolters, John F.; LaBella, Abigail L.; Opulente, Dana A.; Rokas, Antonis; Hittinger, Chris Todd (November 2023, Frontiers in Microbiology)

   IntroductionEukaryotic life depends on the functional elements encoded by both the nuclear genome and organellar genomes, such as those contained within the mitochondria. The content, size, and structure of the mitochondrial genome varies across organisms with potentially large implications for phenotypic variance and resulting evolutionary trajectories. Among yeasts in the subphylum Saccharomycotina, extensive differences have been observed in various species relative to the model yeastSaccharomyces cerevisiae, but mitochondrial genome sampling across many groups has been scarce, even as hundreds of nuclear genomes have become available. MethodsBy extracting mitochondrial assemblies from existing short-read genome sequence datasets, we have greatly expanded both the number of available genomes and the coverage across sparsely sampled clades. ResultsComparison of 353 yeast mitochondrial genomes revealed that, while size and GC content were fairly consistent across species, those in the generaMetschnikowiaandSaccharomycestrended larger, while several species in the order Saccharomycetales, which includesS. cerevisiae, exhibited lower GC content. Extreme examples for both size and GC content were scattered throughout the subphylum. All mitochondrial genomes shared a core set of protein-coding genes for Complexes III, IV, and V, but they varied in the presence or absence of mitochondrially-encoded canonical Complex I genes. We traced the loss of Complex I genes to a major event in the ancestor of the orders Saccharomycetales and Saccharomycodales, but we also observed several independent losses in the orders Phaffomycetales, Pichiales, and Dipodascales. In contrast to prior hypotheses based on smaller-scale datasets, comparison of evolutionary rates in protein-coding genes showed no bias towards elevated rates among aerobically fermenting (Crabtree/Warburg-positive) yeasts. Mitochondrial introns were widely distributed, but they were highly enriched in some groups. The majority of mitochondrial introns were poorly conserved within groups, but several were shared within groups, between groups, and even across taxonomic orders, which is consistent with horizontal gene transfer, likely involving homing endonucleases acting as selfish elements. DiscussionAs the number of available fungal nuclear genomes continues to expand, the methods described here to retrieve mitochondrial genome sequences from these datasets will prove invaluable to ensuring that studies of fungal mitochondrial genomes keep pace with their nuclear counterparts. 

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