Hexokinase expansion in thermophilic snails supports extreme heat tolerance.

Intertidal Echinolittorina snails represent one of the most thermotolerant animal lineages, yet the genomic mechanisms underlying their high-temperature adaptation remain unexplored. Here, we presented chromosome-level genome assemblies for two species, E. malaccana and E. radiata, and explored the genetic toolkit leading to their extreme thermal resistance. Comparative genomic analyses across the animal kingdom uncovered lineage-specific expansion of the hexokinase (HK) family in Echinolittorina snails and their Littorininae relatives. Notably, we discovered a novel type of HK located at the cell membrane through domain fusion, which had not been reported in other animals. Preliminary functional investigations combining multi-omics and cellular assays suggested that these mHKs might support thermotolerance by promoting energy production under thermal stress, with mannose supplementation further enhancing their protective effects, potentially through optimized hexose utilization. Overall, we elucidated new adaptive genome resources and connected these genomic innovations with the extreme thermal adaptation of Echinolittorina snails, providing evolutionary insights into adaptation to extremely hot environments.