Cross-continental venom narratives: proteo-transcriptomic insights into Hydrophis cyanocinctus of India and China.

Hydrophis cyanocinctus, annulated sea snake, is a widely distributed marine elapid whose venom composition and gene-expression architecture remain poorly characterized across its geographic range. Here, we present the first high-resolution proteo-transcriptomic profile of venom and venom gland of this species from India. This research underscores RNA-seq comparison of Indian and Chinese H. cyanocinctus venom gland gene expression to elucidate population-level variation in venom gland machinery, gene diversity, and other regulatory biology. LC–MS/MS profiling of Indian venom identified 2260 peptide hits corresponding to major elapid toxin families. Short-chain three-finger neurotoxins, and myotoxins, along with multiple long-chain neurotoxins, diverse phospholipase A₂ isoforms, and a suite of anti-hemorrhagic and PLA₂/metalloprotease inhibitors were detected, which likely mediate endogenous toxin regulation. Complementary RNA-seq, which generated 191 million reads from the Indian venom gland revealed 16,117 expressed genes. Differentially expressed genes uncovered 7644 up-regulated and 8557 down-regulated genes between populations, with 6089 consistently differentially expressed between HC of India (n = 1) and China (n = 3). Functional enrichment analysis revealed profound upregulation of pathways associated with translation, peptide biosynthesis, ribosome biogenesis, RNA processing, mitochondrial respiration, and ATP synthesis in the Indian population, indicating a hyperactive venom-production state with elevated bioenergetic investment. On the other hand, de novo RNA-Seq assembly and serpent-associated mining recovered ~ 63,000 hits, including expanded repertoires of SVMPs, PLA₂s, and neurotoxins with distinct patterns. Together, these findings demonstrate extensive proteomic and RNA-Seq diversification in H. cyanocinctus, revealing enhanced biosynthetic and metabolic activation in the Indian venom gland, and provide key insights into the venom profile of Indian annulated sea snake.