Transcriptomic shifts contribute to secondary metabolic diversification of Aspergillus flavus populations and the domestication of Aspergillus oryzae

Authors: Drott, Milton; WANG, YEN-WEN - Yale School Of Public Health; HATMAKER, ELIZABETH - University Of Minnesota; MERCADO-SOTO, NAYANNA - University Of Wisconsin; Elmore, James; LUCIANO-ROSARO, DIANIRIS - Oak Ridge National Laboratory; YU, JAE-HYUK - University Of Wisconsin; ROKAS, ANTONIS - Vanderbilt University; GIBBONS, JOHN - University Of Massachusetts, Amherst; HUTTENLOCHER, ANNA - University Of Wisconsin; YANG, KUNLONG - University Of Wisconsin; KELLER, NANCY - University Of Wisconsin

Submitted to: IMA Fungus
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/28/2026
Publication Date: N/A
Citation: N/A

Interpretive Summary: Aspergillus flvaus is a major concern in agriculture because it infects crops and produces aflatoxin, one of the most dangerous natural contaminants of food and feed. This study helps explain how different A. flavus populations vary in their toxin-producing capacity, and how these differences gave rise to Aspergillus oryzae, the fungus used in making soy sauce, miso, and sake. Evidence suggests A. oryzae may have been domesticated more than once from A. flavus populations that were already less prone to producing aflatoxin. We find that key differences between these fungi are not just in their genes, but in how those genes are turned on and off under different environmental conditions. This indicates that toxin risk is shaped not only by genetic background, but also by how fungi respond to ecological pressures such as crop density and environment. Even though A. oryzae dials down aflatoxin genes, it hasn't lost all secondary metabolite activity, and both wild and domesticated strains retain some ability to cause disease under the right circumstances. These findings highlight how fungal populations can shift rapidly in ways that affect virulence and toxin output. A deeper understanding of this regulatory flexibility will help improve mycotoxin management strategies in the field, safeguard crop quality, and reduce risks to food safety and human health.

Technical Abstract: The genomic signatures of microbial domestication are poorly understood in the framework of natural population variation. Here we demonstrate that Aspergillus oryzae, the filamentous fungus used to make soy sauce, shares more-recent ancestry with a largely northern and predominantly non-aflatoxigenic population of Aspergillus flavus, population C. A. oryzae isolates overlaps with the recently described and clinically overrepresented, population D in ways that may suggest multiple domestication events. While A. oryzae shows lower virulence than A. flavus, all isolates tested have retained pathogenicity in zebrafish model of fungal infection. Aspergillus populations are significantly differentiated on a transcriptomic level, a result that shows a significant interaction with population density suggesting population-specific transcriptomes respond differently to ecological shifts. These differences extend beyond differential gene content and cannot always be explained by phylogenetic differentiation, indicating phenotypic diversification may occur through rapid shifts in transcriptomic architectures, e.g., A. oryzae shows significantly higher expression of a transcriptomic module enriched for carbohydrate metabolism. Population-specific differentiation is also evident among secondary metabolite (SM) gene clusters. While A. oryzae shows significantly less expression of some SM genes, particularly aflatoxin, this phenomenon does not extend across the entire secondary metabolome. Constructing machine-learning based gene regulatory networks, we show that population-specific differences in transcriptomic profiles are associated with specific transcription factors, finding evidence of cis and trans population-specific regulatory patterns, but no population-specific changes in global regulatory elements like laeA. Our results offer new insights into the domestication of A. oryzae, its global significance, and the microevolution of secondary metabolism.