Vy-PER: eliminating false positive detection of virus integration events in next generation sequencing data.

Several pathogenic viruses such as hepatitis B and human immunodeficiency viruses may integrate into the host genome. These virus/host integrations are detectable using paired-end next generation sequencing. However, the low number of expected true virus integrations may be difficult to distinguish from the noise of many false positive candidates.

Regulation of polyp-to-jellyfish transition in Aurelia aurita.

Background: The life cycle of scyphozoan cnidarians alternates between sessile asexual polyps and pelagic medusa. Transition from one life form to another is triggered by environmental signals, but the molecular cascades involved in the drastic morphological and physiological changes remain unknown.

Results: We show in the moon jelly Aurelia aurita that the molecular machinery controlling transition of the sessile polyp into a free-swimming jellyfish consists of two parts.

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.

From next-generation sequencing alignments to accurate comparison and validation of single-nucleotide variants: the pibase software.

Scientists working with single-nucleotide variants (SNVs), inferred by next-generation sequencing software, often need further information regarding true variants, artifacts and sequence coverage gaps. In clinical diagnostics, e.g.

Molecular signatures of the three stem cell lineages in hydra and the emergence of stem cell function at the base of multicellularity.

How distinct stem cell populations originate and whether there is a clear stem cell "genetic signature" remain poorly understood. Understanding the evolution of stem cells requires molecular profiling of stem cells in an animal at a basal phylogenetic position. In this study, using transgenic Hydra polyps, we reveal for each of the three stem cell populations a specific signature set of transcriptions factors and of genes playing key roles in cell type-specific function and interlineage communication.

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.

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.

Phylogenomics reveals an anomalous distribution of USP genes in metazoans.

Members of the universal stress protein (USP) family were originally identified in stressed bacteria on the basis of a shared domain, which has since been reported in a phylogenetically diverse range of prokaryotes, fungi, protists, and plants. Although not previously characterized in metazoans, here we report that USP genes are distributed in animal genomes in a unique pattern that reflects frequent independent losses and independent expansions. Multiple USP loci are present in urochordates as well as all Cnidaria and Lophotrochozoa examined, but none were detected in any of the available ecdysozoan or non-urochordate deuterostome genome data.

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.

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.

Activity of the novel peptide arminin against multiresistant human pathogens shows the considerable potential of phylogenetically ancient organisms as drug sources.

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.

More than just orphans: are taxonomically-restricted genes important in evolution?

Comparative genome analyses indicate that every taxonomic group so far studied contains 10-20% of genes that lack recognizable homologs in other species. Do such 'orphan' or 'taxonomically-restricted' genes comprise spurious, non-functional ORFs, or does their presence reflect important evolutionary processes? Recent studies in basal metazoans such as Nematostella, Acropora and Hydra have shed light on the function of these genes, and now indicate that they are involved in important species-specific adaptive processes. Here we focus on evidence from Hydra suggesting that taxonomically-restricted genes play a role in the creation of phylum-specific novelties such as cnidocytes, in the generation of morphological diversity, and in the innate defence system.

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

Background: Despite 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.

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.

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, Hydra's epithelium is remarkably well equipped with potent antimicrobial peptides to prevent pathogen infection.

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.

The evolution of immunity: a low-life perspective.

Several of the key genes and pathways of vertebrate immunity appear to have much earlier origins than has been assumed previously and are present in some of the simplest of true animals. Surveys of recently released whole-genome sequences and large EST (expressed sequence tag) datasets imply that both the canonical Toll/Toll-like receptor (TLR) pathway and a prototypic complement-effector pathway, involving C3 and several membrane attack complex-perforin proteins, are present in corals and sea anemones, members of the basal phylum Cnidaria. However, both pathways are likely to have degenerated substantially in Hydra, leaving open the molecular mechanism by which antimicrobial activities are induced in this cnidarian.

Transgenic stem cells in Hydra reveal an early evolutionary origin for key elements controlling self-renewal and differentiation.

Little is known about stem cells in organisms at the beginning of evolution. To characterize the regulatory events that control stem cells in the basal metazoan Hydra, we have generated transgenics which express eGFP selectively in the interstitial stem cell lineage. Using them we visualized stem cell and precursor migration in real-time in the context of the native environment.

The innate immune repertoire in cnidaria--ancestral complexity and stochastic gene loss.

Background: Characterization of the innate immune repertoire of extant cnidarians is of both fundamental and applied interest--it not only provides insights into the basic immunological 'tool kit' of the common ancestor of all animals, but is also likely to be important in understanding the global decline of coral reefs that is presently occurring. Recently, whole genome sequences became available for two cnidarians, Hydra magnipapillata and Nematostella vectensis, and large expressed sequence tag (EST) datasets are available for these and for the coral Acropora millepora.

Results: To better understand the basis of innate immunity in cnidarians, we scanned the available EST and genomic resources for some of the key components of the vertebrate innate immune repertoire, focusing on the Toll/Toll-like receptor (TLR) and complement pathways.

Molecular phylogenetics in Hydra, a classical model in evolutionary developmental biology.

Among the earliest diverging animal phyla are the Cnidaria. Freshwater polyps of the genus Hydra (Cnidaria, Hydrozoa) have long been of general interest because different species of Hydra reveal fundamental principles that underlie development, differentiation, regeneration and also symbiosis. The phylogenetic relationships among the Hydra species most commonly used in current research are not resolved yet.

Allorecognition in urochordates: identification of a highly variable complement receptor-like protein expressed in follicle cells of Ciona.

The evolutionary origin of allorecognition in vertebrates is unknown. Urochordates, being the closest living relatives of vertebrates [Delsuc F, Brinkmann H, Chourrout D, Philippe H]. Tunicates and not cephalochordates are the closest living relatives of vertebrates.

Dickkopf related genes are components of the positional value gradient in Hydra.

Hydra is a classical model organism to understand fundamental developmental biological processes such as regeneration and axis formation. Here, we show that two genes which share some similarity with members of the Dickkopf family of proteins, HyDkk1/2/4-A and HyDkk1/2/4-C, are co-expressed in gland cells and regulated by the positional value gradient. While HyDkk1/2/4-A is expressed throughout the gastric region, HyDkk1/2/4-C has a graded expression pattern with a high level of transcripts just below the tentacle zone and absence of expression in the budding zone.

Discovery of genes expressed in Hydra embryogenesis.

Hydra's remarkable capacity to regenerate, to proliferate asexually by budding, and to form a pattern de novo from aggregates allows studying complex cellular and molecular processes typical for embryonic development. The underlying assumption is that patterning in adult hydra tissue relies on factors and genes which are active also during early embryogenesis. Previously, we reported that in Hydra the timing of expression of conserved regulatory genes, known to be involved in adult patterning, differs greatly in adults and embryos (Fröbius, A.