Cross-domain transfer of trehalose biosynthesis genes contributes to adaptation in high-altitude environments

High altitudes pose extreme survival challenges for organisms, yet the origins and molecular strategies underlying their resilience remain poorly understood. Here, we report the molecular and evolutionary mechanisms underlying stress resilience in Apourosomoida sp. LHA081A01, a ciliate isolated from a high-altitude Tibetan salt lake that endures high salinity, low temperature, and hypoxia. We identified TreT glycosyltransferases, acquired through horizontal gene transfer from an anaerobic and halophilic Desulfobacteraceae bacterium, to be involved in the synthesis of α,α-trehalose-a universal protein stabilizer absent in most other ciliates but essential for counteracting multiple environmental stressors. Additional strategies include β-carotene accumulation to mitigate oxidative stress from hypoxia, along with numerous others common to many eukaryotes. Extensive gene family expansions and rapid divergence of stress‑responsive genes underscore their evolutionary significance and critical role in surviving harsh habitats. Intolerance to low salinity may render this ciliate, and other protists, vulnerable to climate‑driven salinity declines in Tibetan salt lakes. Together, these extraordinary features-shaped by horizontal gene transfer, natural selection, and regulatory plasticity-position high-altitude microbial eukaryotes as powerful extremophile models for uncovering the molecular mechanisms of stress resilience and adaptive evolution across life.