Biology subjects

Moran, Y.

Publications and source records attributed to Moran, Y..

28 records · Page 2Linked to original sources

bioRxiv2020

Functional characterization of the cnidarian antiviral immune response reveals ancestral complexity

Animals developed a broad repertoire of innate immune sensors and downstream effector cascades for defense against RNA viruses. Yet, this system highly varies between different bilaterian animals, masking its ancestral state. In this study we aimed to characterize the antiviral immune response of the cnidarian Nematostella vectensis and decipher the function of the retinoic acid-inducible gene I-like receptors (RLRs) known to detect viral double-stranded RNA (dsRNA) in bilaterians, but activate different antiviral pathways in vertebrates and nematodes. We show that a mimic of long viral dsRNA triggers a complex antiviral immune response bearing features distinctive for both vertebrate and invertebrate systems. Furthermore, the results of affinity assays and knockdown experiments provide functional evidence for the conserved role of RLRs in initiating immune response to dsRNA that originated before the cnidarian-bilaterian split and lay a strong foundation for future research on the evolution of the immune responses to RNA viruses.

evolutionary biology↗

bioRxiv2020

Sea anemone genomes reveal ancestral metazoan chromosomal macrosynteny

Draft genome sequences of non-bilaterian species have provided important insights into the evolution of the metazoan gene repertoire. However, there is little information about the evolution of gene clusters, genome architectures and karyotypes during animal evolution. In this regard, slowly evolving anthozoan Cnidaria, the sister group of Bilateria, are particularly informative. Here we report chromosome-level genome assemblies of two related cnidarians, the sea anemones Nematostella vectensis and Scolanthus callimorphus. We find a robust set of 15 chromosomes with a clear one-to-one correspondence between the two species. Both sea anemone genomes show remarkable chromosomal conservation with other cnidarians, several bilaterians and the sponge Ephydatia muelleri, allowing us to reconstruct ancestral cnidarian and metazoan chromosomal blocks, consisting of at least 19 and 16 ancestral linkage groups, respectively. We show that, in contrast to Bilateria, the Hox and NK clusters of investigated cnidarians are largely disintegrated, despite the presence of staggered hox/gbx expression in Nematostella. This loss of microsynteny conservation may be facilitated by shorter distances between cis-regulatory sequences and their cognate transcriptional start sites. In line with that, we find no clear evidence for topologically associated domains, suggesting fundamental differences in long-range gene regulation compared to vertebrates. These data suggest that large sets of ancestral metazoan genes have been retained in ancestral linkage groups of some extant lineages, yet, higher order gene regulation with associated 3D architecture may have evolved only after the cnidarian-bilaterian split.

genomics↗

bioRxiv2020

Functional characterization of a "plant-like" HYL1 homolog in the cnidarian Nematostella vectensis indicates a conserved involvement in microRNA biogenesis

While the biogenesis of microRNAs (miRNAs) in both animals and plants depends on the RNase III Dicer, its partner proteins are considered distinct for each kingdom. Nevertheless, recent discovery of homologs of Hyponastic Leaves1 (HYL1), a "plant-specific" Dicer partner, in the metazoan phylum Cnidaria, challenges the view that miRNAs evolved convergently in animals and plants. Here we show that the HYL1 homolog Hyl1-like a (Hyl1La) is crucial for development and miRNA biogenesis in the cnidarian model Nematostella vectensis. Inhibition of Hyl1La by morpholinos resulted in metamorphosis arrest in Nematostella embryos and a significant reduction in levels of most miRNAs. Further, meta-analysis of morphants of miRNA biogenesis components, like Dicer1, shows clustering of their miRNA profiles with Hyl1La morphants. Strikingly, immunoprecipitation of Hyl1La followed by quantitative PCR revealed that in contrast to the plant HYL1, Hyl1La interacts only with precursor miRNAs and not with primary miRNAs. This was complemented by an in vitro binding assay of Hyl1La to synthetic precursor miRNA. Altogether, these results suggest that the last common ancestor of animals and plants carried a HYL1 homolog that took essential part in miRNA biogenesis and indicate early emergence of the miRNA system before plants and animals separated. Impact statementPresence of a functional homolog of HYL1 in Nematostella vectensis, a basal animal model, indicates divergent evolution of miRNA biogenesis pathway in plants and animals from an ancestral miRNA system

evolutionary biology↗

bioRxiv2020

Toxin-like neuropeptides in the sea anemone Nematostella unravel recruitment from the nervous system to venom

The sea anemone Nematostella vectensis (Anthozoa, Cnidaria) is a powerful model system for characterizing the evolution of genes functioning in venom and nervous systems. Despite being an example for evolutionary novelty, the evolutionary origin of most toxins remains unknown. Here we report the first bona fide case of protein recruitment from the cnidarian nervous to venom system. The ShK-like1 peptide has ShKT cysteine motif, is lethal for fish larvae and packaged into nematocysts, the cnidarian venom-producing stinging capsules. Thus, ShK-like1 is a toxic venom component. Its paralog, ShK-like2, is a neuropeptide localized to neurons and is involved in development. Interestingly, both peptides exhibit similarities in their functional activities: both of them provoke contraction in Nematostella polyps and are toxic to fish. Because ShK-like2 but not ShK-like1 is conserved throughout sea anemone phylogeny, we conclude that the two paralogs originated due to a Nematostella-specific duplication of a ShK-like2 ancestor, a neuropeptide-encoding gene, followed by diversification and partial functional specialization. Strikingly, ShK-like2 is represented by two gene isoforms controlled by alternative promoters conferring regulatory flexibility throughout development. Additionally, we characterized the expression patterns of four other peptides with structural similarities to studied venom components, and revealed their unexpected neuronal localization. Thus, we employed genomics, transcriptomics and functional approaches to reveal one new venom component, five neuropeptides with two different cysteine motifs and an evolutionary pathway from nervous to venom system in Cnidaria.

evolutionary biology↗

bioRxiv2020

Population Specific Adaptations in Venom Production to Abiotic Stressors in a Widely Distributed Cnidarian

Nematostella vectensis is a sea anemone (Actiniaria, Cnidaria) inhabiting estuaries over a broad geographic range where environmental conditions such as temperatures and salinity vary widely. In cnidarians, antagonistic interactions with predators and prey are mediated by their venom, which may be metabolically expensive. In this study, we challenged Nematostella polyps with heat, salinity, UV light stressors and a combination of all three to determine how abiotic stressors impact toxin expression for individuals collected across this species range. Transcriptomics and proteomics revealed that the highly abundant toxin Nv1 was the most downregulated gene under heat stress conditions in multiple populations. Physiological measurements demonstrated that venom is metabolically costly to produce suggesting that downregulating venom expression under stressful conditions may be advantageous. Strikingly, under a range of abiotic stressors, individuals from different geographic locations along this latitudinal cline modulate venom production levels differently in a pattern reflecting local adaptation.

evolutionary biology↗

bioRxiv2020

Unravelling the developmental and functional significance of an ancient Argonaute duplication

microRNAs (miRNAs), base-pair to messenger RNA targets and guide Argonaute proteins to mediate their silencing. This target regulation is considered crucial for animal physiology and development. However, this notion is based exclusively on studies in bilaterians, which comprise almost all lab model animals. To fill this glaring phylogenetic gap, we characterized the functions of two Argonaute paralogs in the sea anemone Nematostella vectensis of the phylum Cnidaria, which is separated from bilaterians by [~]600 million years. Using genetic manipulation, Argonaute-immunoprecipitations and high-throughput sequencing we provide experimental evidence for the developmental importance of miRNAs in a non-bilaterian animal. Additionally, we uncover unexpected differential distribution of distinct miRNAs between the two Argonautes and the ability of one of them to load additional types of small RNAs. This enables us to postulate a novel model for evolution of miRNA precursors in sea anemones and their relatives, revealing alternative trajectories for metazoan miRNA evolution.

evolutionary biology↗

bioRxiv2020

Initial virome characterization of the common cnidarian lab model Nematostella vectensis

The role of viruses in forming a stable holobiont has been a subject of extensive research in the recent years. However, many emerging model organisms still lack any data on the composition of the associated viral communities. Here, we re-analyzed seven publicly available transcriptome datasets of the starlet sea anemone Nematostella vectensis, the most commonly used anthozoan lab model, and searched for viral sequences. We applied a straightforward, yet powerful approach of de novo assembly followed by homology-based virus identification and a multi-step, thorough taxonomic validation. The comparison of different lab populations of N. vectensis revealed the existence of the core virome composed of 21 viral sequences, present in all adult datasets. Unexpectedly, we observed almost complete lack of viruses in the samples from the early developmental stages which together with the identification of the viruses shared with the major source of the food in the lab, the brine shrimp Artemia salina, shed new light on the course of viral species acquisition in N. vectensis. Our study provides an initial, yet comprehensive insight into N. vectensis virome and sets the first foundation for functional studies of viruses and antiviral systems in this lab model cnidarian.

evolutionary biology↗

bioRxiv2020

NvPOU4/Brain3 functions as a terminal selector gene in the nervous system of the cnidarian Nematostella vectensis

Terminal selectors are transcription factors that control the morphological, physiological and molecular features that characterize distinct cell types. Here we use expression analyses and a transgenic reporter line to show that NvPOU4 is expressed in post-mitotic cells that give rise to a diverse set of neural cell types in the sea anemone Nematostella vectensis. We generated a loss-of-function allele by CRISPR/Cas9 and used additional transgenic reporter lines to show that the initial specification of neural cells is not affected in the NvPOU4 mutants. Analyses of transcriptomes derived from the mutants and from different neural cell populations revealed that NvPOU4 is required for the execution of the terminal differentiation program of these neural cells. These findings suggest that POU4 genes have ancient functions as terminal selectors for morphologically and functionally highly disparate types of neurons and they provide experimental support for the relevance of terminal selectors for understanding the evolution of cell types.

developmental biology↗

bioRxiv2017

Dynamics of venom composition across a complex life cycle

Little is known about venom in young developmental stages of animals. The appearance of stinging cells in very early life stages of the sea anemone Nematostella vectensis suggests that toxins and venom are synthesized already in eggs, embryos and larvae of this species. Here we harness transcriptomic and biochemical tools as well as transgenesis to study venom production dynamics in Nematostella. We find that the venom composition and arsenal of toxin-producing cells change dramatically between developmental stages of this species. These findings might be explained by the vastly different ecology of the larva and adult polyp as sea anemones develop from a miniature non-feeding mobile planula to a much larger sessile polyp that predates on other animals. Further, the results suggest a much wider and dynamic venom landscape than initially appreciated in animals with a complex life cycle.

evolutionary biology↗

bioRxiv2017

Cell type-specific expression profiling sheds light on the development of a peculiar neuron, housing a complex organelle

Specialized neurons called cnidocytes define the phylum Cnidaria. They possess an explosive organelle called cnidocyst that is important for prey capture and antipredator defense. An extraordinary morphological and functional complexity of the cnidocysts has inspired numerous studies to investigate their structure and development. However, the transcriptomes of the cells bearing these unique organelles are yet to be characterized, impeding our understanding of the genetic basis of their biogenesis. By generating transgenic lines of the sea anemone Nematostella vectensis using the CRISPR/Cas9 system, we have characterized cell-type specific transcriptomic profiles of various stages of cnidocyte maturation and show that nematogenesis (the formation of functional cnidocysts) is underpinned by dramatic shifts in the spatiotemporal gene expression. We also highlight the stark fall in transcriptional-levels of toxin and structural protein coding genes within cnidocytes with the maturation of capsule. We further reveal that the majority of upregulated genes and enriched biochemical pathways specific to cnidocytes are yet to be characterized. Finally, we unravel the recruitment of a metazoan stress-related transcription factor complex into nematogenesis and highlight its role in the formation of a structural protein of the cnidocyst wall. Thus, we provide novel insights into the biology, development, and evolution of cnidocytes.

evolutionary biology↗