Global population genomics redefines domestication and clinical diversity in the Aspergillus flavus–oryzae complex

<i>Aspergillus flavus</i> is a globally important human pathogen and agricultural contaminant, while its domesticated relative <i>A. oryzae</i> is widely used in food fermentation and biotechnology. Despite their importance, the evolutionary relationship, population structure and domestication history of these fungi remain unresolved. Here, we present the first global population genomic analysis of 639 <i>A. flavus</i> and <i>A. oryzae</i> isolates from clinical, environmental and food-fermentation sources across multiple continents. Our analyses reveal a complex evolutionary landscape comprising well-separated clades interspersed with highly admixed mosaic groups and potential evidence for multiple independent domestication events giving rise to <i>A. oryzae</i>. Clinical <i>A. flavus</i> isolates are distributed across several clades and mosaic groups, some overlapping with fermentation strains, highlighting an apparent role of domestication and admixture in shaping pathogen diversity. These results challenge current species boundaries and provide a framework for understanding evolutionary history, taxonomy and pangenomic architecture in these fungi, with broad implications for pathogenicity, food safety, biocontrol and metagenomic surveillance.