Georg Hemmrich

The dynamic genome of Hydra

The freshwater cnidarian Hydra was first described in 1702 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 animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis 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.

Uncovering the evolutionary history of innate immunity: The simple metazoan Hydra uses epithelial cells for host defence

Although many properties of the innate immune system are shared among multicellular animals, the evolutionary origin remains poorly understood. Here we characterize the innate immune system in Hydra, one of the simplest multicellular animals known. In the complete absence of both protective mechanical barriers and mobile phagocytes, Hydras epithelium is remarkably well equipped with potent antimicrobial peptides to prevent pathogen infection. Induction of antimicrobial peptide production is mediated by the interaction of a leucine-rich repeats (LRRs) domain containing protein with a TIR-domain containing protein lacking LRRs. Conventional Toll-like receptors (TLRs) are absent in the Hydra genome. Our findings support the hypothesis that the epithelium represents the ancient system of host defence.

Compagen, a comparative genomics platform for early branching metazoan animals, reveals early origins of genes regulating stem‐cell differentiation

Large‐scale species comparisons at genome and expressed sequence tag (EST) levels have revealed that early branching metazoans such as sponges and cnidarians share many if not most of their genes with the allegedly advanced vertebrates including man. The ancestor of all animals may thus have been much more complex than anticipated. To facilitate and support analysis of genomic and transcriptomic resources in early branching metazoans, we have established a local bio‐computational platform, Compagen (http://www.compagen.org). The platform contains searchable databases with selected raw genomic and EST sequence datasets from sponges and cnidarians up to the lower vertebrates. In addition to the public datasets, Compagen also provides processed data like CAP3 assembled ESTs or predicted peptides. Evaluating the efficacy of the platform by screening for genes reported to be essential in controlling stem‐cell behavior in higher organisms uncovered ancient origins for some but not all components of the vertebrate stem‐cell system. BioEssays 30:1010–1018, 2008.

Defining the origins of the NOD-like receptor system at the base of animal evolution

Distinguishing self from nonself and the onset of defense effector mechanisms upon recognition of pathogens are essential for the survival of all life forms in the animal kingdom. The family of nucleotide -binding and oligomeriszation domain-like receptors (NLRs) was first identified in vertebrates and comprises a group of pivotal sensor protein of the innate immune system for microbial cell wall components or danger signals. Here, we provide first evidence that early diverging metazoans have large and complex NLR repertoires. The cnidarian NACHT/NB-ARC genes include novel combinations of domains, and the number of one specific type (NB-ARC and tetratricopeptide repeat containing) in Hydra is particularly large. We characterize the transcript structure and expression patterns of a selected HyNLR, HyNLR type 1 and describe putative interaction partners. In a heterologous expression system, we show induced proximity recruitment of an effector caspase (HyDD-Caspase) to the HyNLR type 1 protein upon oligomerization indicating a potential role of caspase activation downstream of NLR activation in Hydra. These results add substantially to our understanding of the ancestral innate immune repertoire as well as providing the first insights into putative cytoplasmic defense mechanisms at the base of animal evolution.

The Hydra polyp: Nothing but an active stem cell community

Hydra is a powerful stem cell model because its potential immortality and extensive regeneration capacity is due to the presence of three distinct stem cell lineages. All three lineages conform to a well‐defined spatial distribution across the whole body column of the polyp. Stem cell function in Hydra is controlled by extracellular cues and intrinsic genetic programs. This review focuses on the elusive stem cell niche of the epithelial layers. Based on a comparison of the differences between, and commonalities among, stem cells and stem cell niches in Hydra and other invertebrates and vertebrates, we propose that the whole body column of the polyp may be considered a stem cell “niche” in which stem cell populations are established and signals ensuring the proper balance between stem cells and progenitor cells are integrated. We show that, at over 500 million years old, Hydra offers an early glimpse of the regulatory potential of stem cell niches.

FoxO is a critical regulator of stem cell maintenance in immortal Hydra

Hydra’s unlimited life span has long attracted attention from natural scientists. The reason for that phenomenon is the indefinite self-renewal capacity of its stem cells. The underlying molecular mechanisms have yet to be explored. Here, by comparing the transcriptomes of Hydra’s stem cells followed by functional analysis using transgenic polyps, we identified the transcription factor forkhead box O (FoxO) as one of the critical drivers of this continuous self-renewal. foxO overexpression increased interstitial stem cell and progenitor cell proliferation and activated stem cell genes in terminally differentiated somatic cells. foxO down-regulation led to an increase in the number of terminally differentiated cells, resulting in a drastically reduced population growth rate. In addition, it caused down-regulation of stem cell genes and antimicrobial peptide (AMP) expression. These findings contribute to a molecular understanding of Hydra’s immortality, indicate an evolutionarily conserved role of FoxO in controlling longevity from Hydra to humans, and have implications for understanding cellular aging.

A Novel Gene Family Controls Species-Specific Morphological Traits in Hydra

Understanding the molecular events that underlie the evolution of morphological diversity is a major challenge in biology. Here, to identify genes whose expression correlates with species-specific morphologies, we compared transcriptomes of two closely related Hydra species. We find that species-specific differences in tentacle formation correlate with expression of a taxonomically restricted gene encoding a small secreted protein. We show that gain of function induces changes in morphology that mirror the phenotypic differences observed between species. These results suggest that “novel” genes may be involved in the generation of species-specific morphological traits.

Activity of the Novel Peptide Arminin against Multiresistant Human Pathogens Shows the Considerable Potential of Phylogenetically Ancient Organisms as Drug Sources

ABSTRACT The emergence of multidrug-resistant bacteria highlights the need for new antibacterial agents. Arminin 1a is a novel antimicrobial peptide discovered during investigations of the epithelial defense of the ancient metazoan Hydra. Following proteolytic processing, the 31-amino-acid-long positively charged C-terminal part of arminin 1a exhibits potent and broad-spectrum activity against bacteria, including multiresistant human pathogenic strains, such as methicillin-resistant Staphylococcus aureus (MRSA) strains (minimal bactericidal concentration, 0.4 μM to 0.8 μM). Ultrastructural observations indicate that bacteria are killed by disruption of the bacterial cell wall. Remarkably, the antibacterial activity of arminin 1a is not affected under the physiological salt conditions of human blood. In addition, arminin 1a is a selective antibacterial agent that does not affect human erythrocyte membranes. Arminin 1a shows no sequence homology to any known antimicrobial peptide. Because of its high level of activity against multiresistant bacterial strains pathogenic for humans, the peptide arminin 1a is a promising template for a new class of antibiotics. Our data suggest that ancient metazoan organisms such as Hydra hold promise for the detection of novel antimicrobial molecules and the treatment of infections caused by multiresistant bacteria.

Characterization of taxonomically restricted genes in a phylum-restricted cell type

BackgroundDespite decades of research, the molecular mechanisms responsible for the evolution of morphological diversity remain poorly understood. While current models assume that species-specific morphologies are governed by differential use of conserved genetic regulatory circuits, it is debated whether non-conserved taxonomically restricted genes are also involved in making taxonomically relevant structures. The genomic resources available in Hydra, a member of the early branching animal phylum Cnidaria, provide a unique opportunity to study the molecular evolution of morphological novelties such as the nematocyte, a cell type characteristic of, and unique to, Cnidaria.ResultsWe have identified nematocyte-specific genes by suppression subtractive hybridization and find that a considerable portion has no homologues to any sequences in animals outside Hydra. By analyzing the transcripts of these taxonomically restricted genes and mining of the Hydra magnipapillata genome, we find unexpected complexity in gene structure and transcript processing. Transgenic Hydra expressing the green fluorescent protein reporter under control of one of the taxonomically restricted gene promoters recapitulate faithfully the described expression pattern, indicating that promoters of taxonomically restricted genes contain all elements essential for spatial and temporal control mechanisms. Surprisingly, phylogenetic footprinting of this promoter did not reveal any conserved cis-regulatory elements.ConclusionsOur findings suggest that taxonomically restricted genes are involved in the evolution of morphological novelties such as the cnidarian nematocyte. The transcriptional regulatory network controlling taxonomically restricted gene expression may contain not yet characterized transcription factors or cis-regulatory elements.

Nematogalectin, a nematocyst protein with GlyXY and galectin domains, demonstrates nematocyte-specific alternative splicing in Hydra

Taxonomically restricted genes or lineage-specific genes contribute to morphological diversification in metazoans and provide unique functions for particular taxa in adapting to specific environments. To understand how such genes arise and participate in morphological evolution, we have investigated a gene called nematogalectin in Hydra, which has a structural role in the formation of nematocysts, stinging organelles that are unique to the phylum Cnidaria. Nematogalectin is a 28-kDa protein with an N-terminal GlyXY domain (glycine followed by two hydrophobic amino acids), which can form a collagen triple helix, followed by a galactose-binding lectin domain. Alternative splicing of the nematogalectin transcript allows the gene to encode two proteins, nematogalectin A and nematogalectin B. We demonstrate that expression of nematogalectin A and B is mutually exclusive in different nematocyst types: Desmonemes express nematogalectin B, whereas stenoteles and isorhizas express nematogalectin B early in differentiation, followed by nematogalectin A. Like Hydra, the marine hydrozoan Clytia also has two nematogalectin transcripts, which are expressed in different nematocyte types. By comparison, anthozoans have only one nematogalectin gene. Gene phylogeny indicates that tandem duplication of nematogalectin B exons gave rise to nematogalectin A before the divergence of Anthozoa and Medusozoa and that nematogalectin A was subsequently lost in Anthozoa. The emergence of nematogalectin A may have played a role in the morphological diversification of nematocysts in the medusozoan lineage.