Widespread Saccharomyces hybridization in agave fermentations arises repeatedly from asymmetric parental diversity

Interspecific hybridization can profoundly reshape genomes by bringing together divergent genetic backgrounds, yet its ecological and evolutionary dynamics remain poorly understood at the population level. Here, we identify an extensive hybridization system in traditional agave fermentations across Mexico involving Saccharomyces cerevisiae, a species frequently associated with human-managed environments, and its predominantly wild relative S. paradoxus. A genomic survey reveals unexpectedly high hybrid frequencies in geographically distant regions with contrasting environments. Targeted sampling of distilleries and surrounding natural sites reveals a strong ecological bias, with hybrids recovered almost exclusively from distilleries, although both parental species occur in anthropogenic and natural habitats. Hybrid genomes show extensive architectural diversity, including distinct ploidies, variable parental genome contributions, variable patterns of heterozygosity, and contrasting mitochondrial ancestries. Phylogenomic and population-structure analyses of hybrid subgenomes demonstrate multiple independent origins. These recurrent events show pronounced asymmetry in parental genetic diversity. Hybrids derive from several S. cerevisiae populations, already shaped by extensive introgression, whereas every S. paradoxus subgenome traces to a single genetically differentiated S. paradoxus lineage found exclusively in distilleries, an unexpected association for a predominantly wild species. These findings establish agave fermentations as an exceptional system for studying recurrent interspecific hybridization and reveal how pronounced asymmetry in parental ancestry can shape hybrid formation.