The Portuguese man-of-war genome reveals the genetic basis of medusa loss and sea–air interface adaptation

ABSTRACT The most conspicuous Portuguese man-of-war, Physalia sp., is a neustonic hydromedusa that lacks a free-living medusa stage and features a gas-filled float and venomous tentacles. However, the molecular basis of its specialized niche adaptation remains unknown. Herein, we generated chromosome-level genomes of two neustonic hydromedusae, Physalia utriculus and Porpita porpita (with pelagic medusae). Extensive contractions of neural and muscular gene families were observed for P. utriculus. Loss of Hox1 was correlated with the absence of free-living medusae, and Hox1 knockdown caused abnormal medusa development, suggesting that Hox1 is a key regulator of medusa development in medusazoans. Since it has lost the free-swimming medusa stage, P. utriculus relies on its gas-filled float and toxic tentacles to occupy its ecological niche. Single-cell transcriptomics revealed the mechanism of carbon monoxide production for float inflation. Neurotoxic, cytotoxic, and hemolytic metabolites and toxins were detected in tentacles, and the expanded CtrA gene with toxin domains may enhance its predation and survival. These findings reveal the genetic and cellular adaptations of Physalia to the sea–air interface, elucidating the crucial role that key evolutionary innovations play in shaping unique survival strategies in dynamic marine environments.