Mobilization of the ancient resistome from thawing permafrost

Permafrost, ground frozen for at least two consecutive years, covers nearly one-quarter of the Northern Hemisphere and hosts diverse microbial communities. Climate-driven thaw is releasing preserved microorganisms and genetic material into contemporary ecosystems, where ancient genetic elements may be reintroduced into modern microbes and participate in gene exchange processes. Among these, antibiotic resistance genes (ARGs), which confer resistance to antibiotics, represent a critical yet underrecognized threat. Many originate from ancient microbial ecosystems shaped by natural antibiotic production and resistance, encode mechanisms not yet observed in clinical settings, and are associated with mobile genetic elements (MGEs) that facilitate horizontal gene transfer across microbial domains. Here, we synthesize evolutionary, molecular, and ecological perspectives on the preservation, release, and mobilization of permafrost-derived ARGs. We highlight mineral-DNA interactions that enhance the long-term stability of extracellular DNA containing ARGs and review the roles of MGEs in redistributing resistance determinants following thaw. We discuss conceptual models of rare cross-domain gene transfer and consider ecological and evolutionary implications under thawing conditions. ARG release from permafrost represents a neglected environmental factor that may contribute to antimicrobial resistance (AMR) dynamics and warrants investigation. Finally, identify key knowledge gaps and propose interdisciplinary frameworks for surveillance, risk assessment, and mitigation.