The freshwater cnidarian Hydra was first described in 17021 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals2. Today, Hydra is an important model for studies of axial patterning3, stem cell biology4 and regeneration5. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis6 and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann–Mangold organizer, pluripotency genes and the neuromuscular junction.

The vasa (vas)-related genes are members of the DEAD box protein family and are involved in germ cell formation in higher metazoans. In the present study, we cloned the vas-related genes as well as the PL10-related genes, other members of the DEAD box protein family, from lower metazoans: sponge, Hydra and planaria. The phylogenetic analysis suggested that the vas-related genes arose by duplication of a PL10-related gene before the appearance of sponges but after the diversion of fungi and plants. The vas-related genes in Hydra, Cnvas1 and Cnvas2 were strongly expressed in germline cells and less strongly expressed in multipotent interstitial stem cells and ectodermal epithelial cells. These results suggest that the vas-related genes occur universally among metazoans and that their expression in germline cells was established at least before cnidarian evolution.

The cnidarian freshwater polyp Hydra sp. exhibits an unparalleled regeneration capacity in the animal kingdom. Using an integrative transcriptomic and stable isotope labeling by amino acids in cell culture proteomic/phosphoproteomic approach, we studied stem cell-based regeneration in Hydra polyps. As major contributors to head regeneration, we identified diverse signaling pathways adopted for the regeneration response as well as enriched novel genes. Our global analysis reveals two distinct molecular cascades: an early injury response and a subsequent, signaling driven patterning of the regenerating tissue. A key factor of the initial injury response is a general stabilization of proteins and a net upregulation of transcripts, which is followed by a subsequent activation cascade of signaling molecules including Wnts and transforming growth factor (TGF) beta-related factors. We observed moderate overlap between the factors contributing to proteomic and transcriptomic responses suggesting a decoupled regulation between the transcriptional and translational levels. Our data also indicate that interstitial stem cells and their derivatives (e.g., neurons) have no major role in Hydra head regeneration. Remarkably, we found an enrichment of evolutionarily more recent genes in the early regeneration response, whereas conserved genes are more enriched in the late phase. In addition, genes specific to the early injury response were enriched in transposon insertions. Genetic dynamicity and taxon-specific factors might therefore play a hitherto underestimated role in Hydra regeneration.

The Drosophila gene nanos encodes two particular zinc finger motifs which are also found in germline-associated factors from nematodes to vertebrates. We cloned two nanos (nos)-related genes, Cnnos1 and Cnnos2 from Hydra magnipapillata. Using whole-mount in situ hybridization, the expression of Cnnos1 and Cnnos2 was examined. Cnnos1 was specifically expressed in multipotent stem cells and germline cells, but not in somatic cells. Cnnos2 was weakly expressed in germline cells and more specifically in the endoderm of the hypostome where it appears to be involved in head morphogenesis. In addition to structural conservation in the zinc finger domain of nanos-related genes, functional conservation of Cnnos1 was also demonstrated by the finding that a Cnnos1 transgene can partially rescue the nosRC phenotype that is defective in the egg production of Drosophila. Thus, the function of nanos-related genes in the germline appears to be well conserved from primitive to highly evolved metazoans.