Comparative genomics reveals signatures of distinct metabolic strategies and gene loss associated with Hydra immortality

Hydra is a freshwater cnidarian genus that provides a unique comparative model for aging research, contrasting the immortal H. vulgaris with the aging-inducible H. oligactis. Here, we report a high-quality, chromosome-level genome assembly of H. vulgaris strain AEP.JNIG. Our assembly is comparable in quality to existing resources, facilitating the analysis of genomic diversity across laboratory strains. Epigenomic profiling revealed that gene-body hypermethylation correlates with transcriptional stability and the suppression of spurious transcription in evolutionary conserved genes, suggesting an epigenetic mechanism for genomic integrity. Furthermore, comparative genomics demonstrated that while Hydra conserves fundamental Hallmarks of Aging pathways, the immortal H. vulgaris paradoxically lacks canonical anti-aging genes (e.g., Klotho, NAMPT) found in the aging-inducible H. oligactis. Instead, H. vulgaris exhibits a distinct metabolic signature related to mitochondrial energy production and NTP synthesis. Collectively, our comparative genomics results suggest multiple potential mechanisms associated with the H. vulgaris immortality and the aging traits of H. oligactis, providing novel targets for future functional studies.