Expansion of a single transposable element family is associated with genome-size increase and radiation in the genus Hydra

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Transposable elements are one of the major contributors to genome-size differences in metazoans. Despite this, relatively little is known about the evolutionary patterns of element expansions and the element families involved. Here we report a broad genomic sampling within the genus Hydra, a freshwater cnidarian at the focal point of diverse research in regeneration, symbiosis, biogeography, and aging. We find that the genome of Hydra is the result of an expansion event involving long interspersed nuclear elements and in particular a single family of the chicken repeat 1 (CR1) class. This expansion is unique to a subgroup of the genus Hydra, the brown hydras, and is absent in the green hydra, which has a repeat landscape similar to that of other cnidarians. These features of the genome make Hydra attractive for studies of transposon-driven genome expansions and speciation

Incorporation of a Horizontally Transferred Gene into an Operon during Cnidarian Evolution

Genome sequencing has revealed examples of horizontally transferred genes, but we still know little about how such genes are incorporated into their host genomes. We have previously reported the identification of a gene (flp) that appears to have entered the Hydra genome through horizontal transfer. Here we provide additional evidence in support of our original hypothesis that the transfer was from a unicellular organism, and we show that the transfer occurred in an ancestor of two medusozoan cnidarian species. In addition we show that the gene is part of a bicistronic operon in the Hydra genome. These findings identify a new animal phylum in which trans-spliced leader addition has led to the formation of operons, and define the requirements for evolution of an operon in Hydra. The identification of operons in Hydra also provides a tool that can be exploited in the construction of transgenic Hydra strains

FoxO and Stress Responses in the Cnidarian Hydra vulgaris

Background: In the face of changing environmental conditions, the mechanisms underlying stress responses in diverse organisms are of increasing interest. In vertebrates, Drosophila, and Caenorhabditis elegans, FoxO transcription factors mediate cellular responses to stress, including oxidative stress and dietary restriction. Although FoxO genes have been identified in early-arising animal lineages including sponges and cnidarians, little is known about their roles in these organisms. Methods/Principal Findings: We have examined the regulation of FoxO activity in members of the well-studied cnidarian genus Hydra. We find that Hydra FoxO is expressed at high levels in cells of the interstitial lineage, a cell lineage that includes multipotent stem cells that give rise to neurons, stinging cells, secretory cells and gametes. Using transgenic Hydra that express a FoxO-GFP fusion protein in cells of the interstitial lineage, we have determined that heat shock causes localization of the fusion protein to the nucleus. Our results also provide evidence that, as in bilaterian animals, Hydra FoxO activity is regulated by both Akt and JNK kinases. Conclusions: These findings imply that basic mechanisms of FoxO regulation arose before the evolution of bilaterians an

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Model systems for environmental signaling

Studies of environmental signaling in animals have focused primarily on organisms with relatively constrained responses, both temporally and phenotypically. In this regard, existing model animals (e.g., worms and flies ) are particularly extreme. Such animals have relatively little capacity to alter their morphology in response to environmental signals. Hence, they exhibit little phenotypic plasticity. On the other hand, basal metazoans exhibit relatively unconstrained responses to environmental signals and may thus provide more general insight, insofar as these constraints are likely traits derived during animal evolution. Such enhanced phenotypic plasticity may result from greater sensitivity to environmental signals, or greater abundance of suitable target cells, or both. Examination of what is known of the components of environmental signaling pathways in cnidarians reveals many similarities to well-studied model animals. In addition to these elements, however, macroscopic basal metazoans (e.g., sponges and cnidarians) typically exhibit a system-level capability for integrating environmental information. In cnidarians, the gastrovascular system acts in this fashion, generating local patterns of signaling (e.g., pressure, shear, and reactive oxygen species) via its organism-wide functioning. Contractile regions of tissue containing concentrations of mitochondrion-rich, epitheliomuscular cells may be particularly important in this regard, serving in both a functional and a signaling context. While the evolution of animal circulatory systems is usually considered in terms of alleviating surface-to-volume constraints, such systems also have the advantage of enhancing the capacity of larger organisms to respond quickly and efficiently to environmental signals. More general features of animals that correlate with relatively unconstrained responses to environmental signals (e.g., active stem cells at all stages of the life cycle) are also enumerated and discussed

Incorporation of a Horizontally Transferred Gene into an Operon during Cnidarian Evolution

Genome sequencing has revealed examples of horizontally transferred genes, but we still know little about how such genes are incorporated into their host genomes. We have previously reported the identification of a gene (flp) that appears to have entered the Hydra genome through horizontal transfer. Here we provide additional evidence in support of our original hypothesis that the transfer was from a unicellular organism, and we show that the transfer occurred in an ancestor of two medusozoan cnidarian species. In addition we show that the gene is part of a bicistronic operon in the Hydra genome. These findings identify a new animal phylum in which trans-spliced leader addition has led to the formation of operons, and define the requirements for evolution of an operon in Hydra. The identification of operons in Hydra also provides a tool that can be exploited in the construction of transgenic Hydra strains

Incorporation of a horizontally transferred gene into an operon during cnidarian evolution

Genome sequencing has revealed examples of horizontally transferred genes, but we still know little about how such genes are incorporated into their host genomes. We have previously reported the identification of a gene (flp) that appears to have entered the Hydra genome through horizontal transfer. Here we provide additional evidence in support of our original hypothesis that the transfer was from a unicellular organism, and we show that the transfer occurred in an ancestor of two medusozoan cnidarian species. In addition we show that the gene is part of a bicistronic operon in the Hydra genome. These findings identify a new animal phylum in which trans-spliced leader addition has led to the formation of operons, and define the requirements for evolution of an operon in Hydra. The identification of operons in Hydra also provides a tool that can be exploited in the construction of transgenic Hydra strains. © 2012 Dana et al

Variations on a theme? Polyp and medusa development in Podocoryna carnea

The life cycles of many cnidarian species are notable for including two stages with very different morphologies - sessile polyp and swimming medusa. Cnidarians thus provide an opportunity to study the developmental bases of differences in body organization without the need to compare organisms of different taxa. Information about the two life cycle stages suggests the following questions about differences in their development. (1) Are the mouth and tentacle-bearing region (bell margin) specified using any of the same molecular mechanisms as in the polyp? (2) Has the oral-aboral axis of the medusa been truncated relative to that of the polyp by elimination of molecular processes specifying aboral tissue identity? (3) Is the elongated region between the hydrozoan medusa mouth and tentacle ring (the manubrium) patterned using processes that pattern the entire oral-aboral axis in the polyp? We describe how data on their expression of FoxA, NK-2, and Emx genes during polyp and medusa development, together with reagents targeting specific signaling pathways, could be used to address these questions. We have isolated portions of a FoxA2 homologue, an NK-2 gene, and two Emx genes from Podocoryna carnea Sars, an experimentally tractable hydrozoan with both polyp and medusa stages. Phylogenetic analyses indicate that the two P. carnea Emx genes are the result of a gene duplication

RFC140/<i>flp</i> exon-intron organization (A) and intergenic region sequence (B).

<p>The RFC140 gene exons are shown in black. The single <i>flp</i> exon and 3′ UTR are shown in red and white respectively. The coding sequence of the RFC140 gene has been deposited in GenBank under accession number FJ154842. Annotations in Panel B are as follows: gray, RFC140 stop codon and <i>flp</i> start codon; green, putative polyadenylation signal; double-underline, T-rich sequence; single-underline, polypyrimidine tract associated with the trans-splicing acceptor dinucleotide; blue, trans-splicing acceptor dinucleotide; yellow, additional AG dinucleotides changed to AA in mutant plasmid.</p