This study is led by Professor Yun‑Wei Dong (Ocean University of China). The researchers aim to explore the genomic mechanisms underlying the remarkable heat tolerance of Echinolittorina snails, which are tiny intertidal creatures yet can survive temperatures exceeding 55 °C, making them among the most thermotolerant animals known.
The team first constructed chromosome‑level genomes for two sympatric species along China's coast, E. malaccana and E. radiata , using PacBio HiFi and Hi‑C sequencing. These high‑quality resources revealed a dramatic expansion of the HK gene family, the gatekeepers of glycolysis, with up to 36 HK genes in Echinolittorina , the highest number ever observed across animal genomes from 18 phyla. “We were surprised to see such a massive expansion of a single metabolic gene family,” Chao-Yi Ma says, the first author. “It immediately hinted that these snails had evolved a unique genomic strategy, related to energy metabolism, to cope with extreme heat.”
Further evolutionary analyses showed that this expansion occurred exclusively within a specific HK subfamily (IIB) through tandem duplications, and it was accompanied by remarkable structural innovations. Many of these duplicated genes acquired new N‑terminal extensions via domain fusion. Using deep‑learning predictions and confocal microscopy, the researchers excitedly found that the new domain acquired by these isoforms was the Ig-like domain, thus generating novel HKs anchored to the cell membrane (mHKs), whereas all other known animal HKs are either cytoplasmic or linked to outer membrane of mitochondrion. “This is the first documented case of membrane‑localized HKs in any animal,” explains Professor Dong. “It represents a completely new way for animal cells to position this fundamental metabolic enzyme.”
To test the functional significance of these mHKs, the team transiently expressed them in HEK293T cells and subjected the cells to heat stress. They found that cells expressing mHKs had higher viability than controls, especially when pre‑treated with mannose, a sugar abundant in the microalgae that Echinolittorina snails feed on in their natural habitats. Metabolic profiling further showed that mHKs enhance hexose catabolism and ATP production, with mannose supplementation further enhancing this beneficial effect. The team therefore proposes that the emergence of mHKs may provide a key adaptive advantage for Echinolittorina snails living in the harsh high‑intertidal zone, where daily temperatures can often exceed 50 °C in summer and feeding is restricted to brief high‑tide windows. By optimizing energy production, mHKs likely help support the elevated energy demands of heat‑stress responses during prolonged low‑tide exposure.
Looking ahead, the researchers note that the chromosome‑level genomes they have generated will serve as valuable resources for studying thermal adaptation in intertidal organisms. They also emphasize the need for further studies to fully understand the functions of mHKs in vivo . “While our current findings are exciting, they are only the beginning,” adds Chao-Yi Ma. “We hope this study encourages others to further explore the hidden molecular mechanisms that allow these tiny creatures to thrive under the most extreme conditions on our planet.”
See the article:
Hexokinase expansion in thermophilic snails supports extreme heat tolerance
https://doi.org/10.1007/s11427-025-3320-5
Science China Life Sciences