Physiological Adaptations to Freeze Tolerance in Ectothermic Vertebrates

Freezing presents a profound challenge to ectothermic vertebrates, as ice formation can disrupt cellular integrity and metabolic homeostasis. To survive whole-body freezing, species such as certain frogs and reptiles employ a coordinated suite of adaptations. Ice is confined to extracellular spaces, preventing intracellular crystallisation, while cryoprotectants—small solutes like glucose, glycerol and urea—accumulate to balance osmotic pressure and limit cell shrinkage. Metabolic rate is sharply depressed, conserving energy reserves and reducing the need for oxygen. At the molecular level, shifts in enzyme activities, reversible post-translational modifications and targeted gene expression ensure that critical pathways remain poised for rapid reactivation upon thawing. Concurrently, antioxidant systems and anti-apoptotic responses guard against damage from reactive oxygen species and cell death during freeze–thaw cycles. Recent advances in proteomic, transcriptomic and metabolomic profiling have revealed extensive seasonal remodelling of liver and muscle biochemistry, illuminating how signal transduction, stress-response proteins and energy metabolism are rewired in the frozen state. Together, these mechanisms underpin the extraordinary resilience of freeze-tolerant vertebrates and offer insights relevant to cryopreservation, conservation biology and our understanding of life in extreme environments.

Research from Nature Portfolio

Proteomic analysis of liver tissue from freeze-tolerant wood frogs identified nearly 90 proteins whose abundance shifts in response to freezing, dehydration and anoxia. Key enzymes including glutathione S-transferase, aldolase and sorbitol dehydrogenase were upregulated and displayed elevated catalytic activity in frozen and oxygen-deprived groups, suggesting roles in detoxification and energy management under ice-induced stress. Post-translational control appears central to the rapid deployment of these protective enzymes.

An investigation of Siberian wood frogs demonstrated survival for over 90 days in water with oxygen levels below 0.2 mg L⁻¹ at 2–3 °C, retaining responsiveness despite prolonged extreme hypoxia. This work highlights a convergence of hypoxia and freeze tolerance mechanisms, expanding our view of how vertebrates endure subzero aquatic environments without succumbing to oxygen deprivation.

Physiological Adaptations to Freeze Tolerance in Ectothermic Vertebrates publication trend

The graph below shows the total number of articles in physiological adaptations to freeze tolerance in ectothermic vertebrates across all publications each year (not limited to Nature Index journals).

Technical terms

Cryoprotectant: A small solute that stabilises cells by balancing osmotic pressure and preventing intracellular ice formation during freezing.

Hypometabolism: A regulated reduction in metabolic rate that decreases energy and oxygen demands under severe environmental stress.

Proteomics: The large-scale analysis of proteins, including their expression levels, modifications and interactions.

Transcriptomics: The study of RNA transcripts to determine gene expression changes under specific conditions.

Reversible protein phosphorylation: The addition and removal of phosphate groups on proteins, modulating their activity in response to stimuli.

References

1. Proteomic analysis of Rana sylvatica reveals differentially expressed proteins in liver in response to anoxia, dehydration or freezing stress. Scientific Reports (2024).
2. Surviving winter on the Qinghai-Xizang Plateau: Extensive reversible protein phosphorylation plays a dominant role in regulating hypometabolism in hibernating Nanorana parkeri. 动物学研究 (2024).
3. Comparative transcriptomic analysis delineates adaptation strategies of Rana kukunoris toward cold stress on the Qinghai-Tibet Plateau. BMC Genomics (2024).
4. The Siberian wood frog survives for months underwater without oxygen. Scientific Reports (2019).