Turritopsis dohrnii is the only metazoan enable to rejuvenate repeatedly after its medusae reproduces, which challenges our understanding of aging as this organism apparently reaches biological immortality. In this study, we present the whole-genome sequences of T. dohrnii and its congeneric species, Turritopsis rubra, and compare them to better understand the molecular mechanisms that could promote its immortal phenotype. Using automatic and manually supervised annotations, together with the transcriptome of the life cycle reversal (LCR) of T. dohrnii, we have identified differential residue variations and expansions of genes associated with replication efficiency, DNA repair, telomere maintenance, as well as genes involved in maintaining redox environment, stem cell population and intercellular communication. Most of these genes are transcriptionally active during the LCR. Moreover, we have identified both the silencing of Polycomb repressive complex 2 targets and the activation of pluripotency targets during the LCR process, which points to these transcription factors as candidates to induce pluripotency in T. dohrnii. Accordingly, we propose these factors as key elements in the ability of T. dohrnii to undergo rejuvenation.
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