Genomic Potential and Climate Resilience of Agave angustifolia Haworth in Raicilla Production

Agave angustifolia Haw. is one of the primary sources for the production of mezcals such as raicilla and tuxca, in western Mexico. In Jalisco, Agave angustifolia evolved from being a pre-Hispanic ritual and food resource (200–1500 CE) to becoming the primary basis for 16th-century vino mezcal, the precursor to all modern mezcals, including raicilla and tequila. This review synthesizes current genomic, epigenetic, and metabolic evidence to elucidate the species’ evolutionary and adaptive potential. Our analysis suggests that the domestication of A. angustifolia is characterized by a “domestication paradox,” where intensive clonal management ensures short-term productivity but creates genetic bottlenecks that limit long-term adaptive capacity. We synthesize empirical evidence to show that adaptive plasticity is driven by the integration of Crassulacean Acid Metabolism (CAM) flexibility and dynamic global DNA methylation (GDM) profiles, which, while currently correlative, suggest an environmental response mechanism. We conclude that securing the socio-economic viability of Agave spirits requires a transition from intensive monocultures to regenerative agroforestry, incorporating sexual propagation to maintain evolutionary potential. Furthermore, we outline a roadmap for Genomics-Assisted Breeding (GAB 4.0), integrating marker-assisted selection for juvenile traits to accelerate the release of resilient biotypes, and precision diagnostic tools to reduce the ecological footprint of Agave production. This framework secures the genomic integrity of traditional spirits within a circular, climate-resilient bioeconomy.