Biology subjects

Drott, M. T.

Publications and source records attributed to Drott, M. T..

7 recordsLinked to original sources

bioRxiv2025

Population-Specific Transcriptomic Shifts Underlie Secondary Metabolic Diversification in Aspergillus flavus and the Domestication of Aspergillus oryzae

The genomic signatures of microbial domestication remain poorly understood within the context of natural population variation. Here, we demonstrate that Aspergillus oryzae, the filamentous fungus used in soy sauce production, shares more recent ancestry with a predominantly northern, largely non-aflatoxigenic population of Aspergillus flavus (population C). Strikingly, A. oryzae isolates also overlap with the recently described, clinically enriched A. flavus population D, suggesting the possibility of multiple domestication events. Although A. oryzae exhibits reduced virulence compared to A. flavus, all isolates tested retained pathogenicity in a zebrafish infection model. At the transcriptomic level, Aspergillus populations are significantly differentiated, with distinct responses to population density, indicating that population-specific transcriptomes adapt differently to ecological conditions. These differences extend beyond gene content and are not always explained by phylogenetic relationships, suggesting that phenotypic diversification occurs through the rapid reorganization of transcriptomic architectures. For example, A. oryzae displays significantly elevated expression of a module enriched for carbohydrate metabolism. Population-specific variation is also evident among secondary metabolite (SM) gene clusters. While A. oryzae shows markedly reduced expression of specific SM genes, particularly those involved in aflatoxin biosynthesis, this trend does not extend across the entire secondary metabolome. Using machine- learning-based gene regulatory network inference, we identified population-specific transcriptomic differences linked to distinct transcription factors, with evidence for both cis- and trans-acting regulatory divergence, but no changes in global regulators such as laeA. Together, these findings provide new insights into the domestication of A. oryzae, its global significance, and the microevolution of fungal secondary metabolic pathways. Significance StatementAspergillus flavus poses a significant threat to global agriculture by infecting crops and producing aflatoxin, a potent carcinogen that undermines food safety and international trade. The species is also a major human pathogen causing invasive fungal infections. Here, we demonstrate that A. flavus populations exhibit not only variations in their capacity to produce toxins but also in the way they regulate gene expression in response to environmental cues. These regulatory differences played a key role in the domestication of Aspergillus oryzae, a non-aflatoxigenic relative that has been safely used in food fermentation for centuries. Notably, while A. oryzae exhibits reduced aflatoxin biosynthetic gene expression, it expresses other secondary metabolite genes and retains limited opportunistic pathogenic potential. By revealing how transcriptomic rewiring drives population-level divergence, this work provides new insights into the evolution of toxin production, with broad implications for microbial domestication, crop protection, and global food security.

microbiology↗

bioRxiv2024

Biosynthetic Gene Cluster Diversity Across Native and Introduced Populations of an Ectomycorrhizal Fungus, Suillus luteus

Non-pathogenic fungi are being increasingly recognized for their involvement in biological invasions, where they have the potential to cause ecological and economical harm. One notable example is the ectomycorrhizal (EcM) fungus, Suillus luteus, which is commonly found co-invading with non-native pines that have escaped from commercial pine plantations across the Southern Hemisphere. In such invasions, selection pressures imposed by novel plants, soil microbes, and environmental conditions, as well as impoverished assemblages of co-invading EcM fungi, may exert particularly strong selective effects and contribute to driving evolutionary divergence in traits. We investigated the potential impact of this global co-introduction on biosynthetic gene cluster (BGC) diversity in native and introduced populations of S. luteus. We found that native populations demonstrated higher BGC diversity at both the gene and clan levels compared to introduced populations. Additionally, we identified a collection of unique BGCs as well as 24 highly conserved clans, including two featuring known pathways, within both native and introduced populations. Furthermore, our study confirmed the presence of three previously identified clades of S. luteus with distinct gene cluster family (GCF) diversity. Thus, our study concludes that the introduction of S. luteus has driven evolutionary changes in its BGCs, underscoring the broader implications of global co-introductions on fungal adaptation in new environments.

evolutionary biology↗

bioRxiv2024

Variation in Biosynthetic Gene Clusters Among Lifestyles Across Kingdom Fungi

Biosynthetic gene clusters (BGCs) produce secondary metabolites, many of which are involved in trophic interactions and carbon acquisition lifestyles of fungi. As such, BGCs are hypothesized to exhibit evolutionary diversification across those lifestyles. We tested this hypothesis by analyzing predicted BGCs in more than 1000 fungal genomes, and their variation among fungal lineages and across putative fungal lifestyles (trophic modes). Analyses revealed that specific BGC classes, such as PKSI, RiPPs, and terpenes, exhibit significant phylogenetic signals, whereas others, like NRPS and PKS-NRPS Hybrids, do not. BGC abundance was associated with fungal lifestyles: pathotrophs generally had lower BGC abundance, while combined lifestyles such as saprotroph-symbiotrophs had higher BGC abundances. These findings suggest that both phylogenetic history and ecological strategies drive BGC distribution, highlighting their roles in fungal biochemical diversification. Understanding these patterns provides insights into fungal community ecology and the evolutionary processes shaping their biosynthetic potential.

genomics↗

bioRxiv2024

Pathogenicity is associated with population structure in a fungal pathogen of humans

Aspergillus flavus is a clinically and agriculturally important saprotrophic fungus responsible for severe human infections and extensive crop losses. We analyzed genomic data from 250 (95 clinical and 155 environmental) A. flavus isolates from 9 countries, including 70 newly sequenced clinical isolates, to examine population and pan-genome structure and their relationship to pathogenicity. We identified five A. flavus populations, including a new population, D, corresponding to distinct clades in the genome-wide phylogeny. Strikingly, > 75% of clinical isolates were from population D. Accessory genes, including genes within biosynthetic gene clusters, were significantly more common in some populations but rare in others. Population D was enriched for genes associated with zinc ion binding, lipid metabolism, and certain types of hydrolase activity. In contrast to the major human pathogen Aspergillus fumigatus, A. flavus pathogenicity in humans is strongly associated with population structure, making it a great system for investigating how population-specific genes contribute to pathogenicity.

evolutionary biology↗

bioRxiv2023

Mining for a New Class of Fungal Natural Products: The Evolution, Diversity, and Distribution of Isocyanide Synthase Biosynthetic Gene Clusters

The products of non-canonical isocyanide synthase (ICS) biosynthetic gene clusters (BGCs) have notable bioactivities that mediate pathogenesis, microbial competition, and metal-homeostasis through metal-associated chemistry. We sought to enable research into this class of compounds by characterizing the biosynthetic potential and evolutionary history of these BGCs across the Fungal Kingdom. We developed the first genome-mining pipeline to identify ICS BGCs, locating 3,800 ICS BGCs in 3,300 genomes. Genes in these clusters share promoter motifs and are maintained in contiguous groupings by natural selection. ICS BGCs are not evenly distributed across fungi, with evidence of gene-family expansions in several Ascomycete families. We show that the ICS dit1/2 gene cluster family (GCF), which was thought to only exist in yeast, is present in [~]30% of all Ascomycetes, including many filamentous fungi. The evolutionary history of the dit GCF is marked by deep divergences and phylogenetic incompatibilities that raise questions about convergent evolution and suggest selection or horizontal gene transfers have shaped the evolution of this cluster in some yeast and dimorphic fungi. Our results create a roadmap for future research into ICS BGCs. We developed a website (www.isocyanides.fungi.wisc.edu) that facilitates the exploration, filtering, and downloading of all identified fungal ICS BGCs and GCFs.

microbiology↗

bioRxiv2022

Fungal antibiotics control bacterial community diversity in the cheese rind microbiome

Potent antimicrobial metabolites are produced by filamentous fungi in pure lab cultures, but their ecological functions in nature are often unknown. Using an antibiotic-producing Penicillium isolate and the cheese rind microbial community, we demonstrate that a fungal specialized metabolite can regulate the diversity of bacterial communities. Inactivation of the global regulator, LaeA, resulted in the loss of antibacterial activity in the Penicillium isolate. Cheese rind bacterial communities assembled with the laeA deletion strain had significantly higher bacterial abundances than the wild-type strain. RNA-sequencing and metabolite profiling demonstrated a striking reduction in the expression and production of the natural product pseurotin in the laeA deletion strain. Inactivation of a core gene in the pseurotin biosynthetic cluster restored bacterial community composition, demonstrating the role of pseurotins in mediating bacterial community assembly. Our discovery demonstrates how antibiotic production can drive the assembly of microbiomes and provides an ecological context for widespread fungal specialized metabolites.

microbiology↗

bioRxiv2020

An Interpreted Atlas of Biosynthetic Gene Clusters from 1000 Fungal Genomes

Fungi are prolific producers of natural products, compounds which have had a large societal impact as pharmaceuticals, mycotoxins, and agrochemicals. Despite the availability of over 1000 fungal genomes and several decades of compound discovery efforts from fungi, the biosynthetic gene clusters (BGCs) encoded by these genomes and the associated chemical space have yet to be analyzed systematically. Here we provide detailed annotation and analyses of fungal biosynthetic and chemical space to enable genome mining and discovery of fungal natural products. Using 1037 genomes from species across the fungal kingdom (e.g., Ascomycota, Basidiomycota, and non-Dikarya taxa), 36,399 predicted BGCs were organized into a network of 12,067 gene cluster families (GCFs). Anchoring these GCFs with reference BGCs enabled automated annotation of 2,026 BGCs with predicted metabolite scaffolds. We performed parallel analyses of the chemical repertoire of Fungi, organizing 15,213 fungal compounds into 2,945 molecular families (MFs). The taxonomic landscape of fungal GCFs is largely species-specific, though select families such as the equisetin GCF are present across vast phylogenetic distances with parallel diversifications in the GCF and MF. We compare these fungal datasets with a set of 5,453 bacterial genomes and their BGCs and 9,382 bacterial compounds, revealing dramatic differences between bacterial and fungal biosynthetic logic and chemical space. These genomics and cheminformatics analyses reveal the large extent to which fungal and bacterial sources represent distinct compound reservoirs. With a >10-fold increase in the number of interpreted strains and annotated BGCs, this work better regularizes the biosynthetic potential of fungi for rational compound discovery. Significance StatementFungi represent an underexploited resource for new compounds with applications in the pharmaceutical and agriscience industries. Despite the availability of >1000 fungal genomes, our knowledge of the biosynthetic space encoded by these genomes is limited and ad hoc. We present results from systematically organizing the biosynthetic content of 1037 fungal genomes, providing a resource for data-driven genome mining and large-scale comparison of the genetic and molecular repertoires produced in fungi and compare to those present in bacteria.

biochemistry↗