Environmental adaptation and functional diversity of calcin peptides from the venom of East Asian scorpions

Toxins as naturally occurring hazardous substances, have evolved as a defense mechanism in organisms for survival. The expression of toxins is profoundly influenced by environmental factors, and the investigation of their correlation holds significant implications for understanding toxin-induced harm and developing protective measures. Scorpions are a significant venomous species, and the relationship between the variability in scorpion toxin expression and environmental factors remains unclear. By conducting transcriptome profiling of scorpion samples collected from eight distinct climatic and environmental regions in East Asia, we successfully identified two distinct scorpion species. Furthermore, we found that the divergence in toxin composition, specifically the expression of two recently discovered calcins are closely aligned with the environmental humidity of their respective habitats. These calcins exhibited varying capacities to modulate the binding affinity of [ 3 H]ryanodine to ryanodine receptors, inducing prolonged subconductance states. Our findings demonstrate that the distinct toxin arsenals of these scorpions reflect long-term adaptive evolution to their specific climatic niches. This study underscores the importance of considering ecological factors in understanding the evolutionary diversification of venomous species, providing a theoretical foundation for the rational exploration of natural toxins in traditional Chinese medicine and drug discovery. • Unigene diversity in East Asian scorpions is closely associated with regional humidity gradients. • Toxin expression profiles exhibit significant correlation with environmental factors across distinct populations. • Two novel calcins reflect species-specific adaptation to humid and arid environments. • Two novel calcins demonstrated varying levels of efficacy in the binding affinity of RyR1.