Noa Sher

Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax

The blind mole rat (BMR), Spalax galili, is an excellent model for studying mammalian adaptation to life underground and medical applications. The BMR spends its entire life underground, protecting itself from predators and climatic fluctuations while challenging it with multiple stressors such as darkness, hypoxia, hypercapnia, energetics and high pathonecity. Here we sequence and analyse the BMR genome and transcriptome, highlighting the possible genomic adaptive responses to the underground stressors. Our results show high rates of RNA/DNA editing, reduced chromosome rearrangements, an over-representation of short interspersed elements (SINEs) probably linked to hypoxia tolerance, degeneration of vision and progression of photoperiodic perception, tolerance to hypercapnia and hypoxia and resistance to cancer. The remarkable traits of the BMR, together with its genomic and transcriptomic information, enhance our understanding of adaptation to extreme environments and will enable the utilization of BMR models for biomedical research in the fight against cancer, stroke and cardiovascular diseases.

Transcriptome profiling of the dynamic life cycle of the scypohozoan jellyfish Aurelia aurita

BackgroundThe moon jellyfish Aurelia aurita is a widespread scyphozoan species that forms large seasonal blooms. Here we provide the first comprehensive view of the entire complex life of the Aurelia Red Sea strain by employing transcriptomic profiling of each stage from planula to mature medusa.ResultsA de novo transcriptome was assembled from Illumina RNA-Seq data generated from six stages throughout the Aurelia life cycle. Transcript expression profiling yielded clusters of annotated transcripts with functions related to each specific life-cycle stage. Free-swimming planulae were found highly enriched for functions related to cilia and microtubules, and the drastic morphogenetic process undergone by the planula while establishing the future body of the polyp may be mediated by specifically expressed Wnt ligands. Specific transcripts related to sensory functions were found in the strobila and the ephyra, whereas extracellular matrix functions were enriched in the medusa due to high expression of transcripts such as collagen, fibrillin and laminin, presumably involved in mesoglea development. The CL390-like gene, suggested to act as a strobilation hormone, was also highly expressed in the advanced strobila of the Red Sea species, and in the medusa stage we identified betaine-homocysteine methyltransferase, an enzyme that may play an important part in maintaining equilibrium of the medusa’s bell. Finally, we identified the transcription factors participating in the Aurelia life-cycle and found that 70% of these 487 identified transcription factors were expressed in a developmental-stage-specific manner.ConclusionsThis study provides the first scyphozoan transcriptome covering the entire developmental trajectory of the life cycle of Aurelia. It highlights the importance of numerous stage-specific transcription factors in driving morphological and functional changes throughout this complex metamorphosis, and is expected to be a valuable resource to the community.

Early and late response of Nematostella vectensis transcriptome to heavy metals

Environmental contamination from heavy metals poses a global concern for the marine environment, as heavy metals are passed up the food chain and persist in the environment long after the pollution source is contained. Cnidarians play an important role in shaping marine ecosystems, but environmental pollution profoundly affects their vitality. Among the cnidarians, the sea anemone Nematostella vectensis is an advantageous model for addressing questions in molecular ecology and toxicology as it tolerates extreme environments and its genome has been published. Here, we employed a transcriptome‐wide RNA‐Seq approach to analyse N. vectensis molecular defence mechanisms against four heavy metals: Hg, Cu, Cd and Zn. Altogether, more than 4800 transcripts showed significant changes in gene expression. Hg had the greatest impact on up‐regulating transcripts, followed by Cu, Zn and Cd. We identified, for the first time in Cnidaria, co‐up‐regulation of immediate‐early transcription factors such as Egr1, AP1 and NF‐κB. Time‐course analysis of these genes revealed their early expression as rapidly as one hour after exposure to heavy metals, suggesting that they may complement or substitute for the roles of the metal‐mediating Mtf1 transcription factor. We further characterized the regulation of a large array of stress‐response gene families, including Hsp, ABC, CYP members and phytochelatin synthase, that may regulate synthesis of the metal‐binding phytochelatins instead of the metallothioneins that are absent from Cnidaria genome. This study provides mechanistic insight into heavy metal toxicity in N. vectensis and sheds light on ancestral stress adaptations.

A New N -Acyl Homoserine Lactone Synthase in an Uncultured Symbiont of the Red Sea Sponge Theonella swinhoei

ABSTRACT Sponges harbor a remarkable diversity of microbial symbionts in which signal molecules can accumulate and enable cell-cell communication, such as quorum sensing (QS). Bacteria capable of QS were isolated from marine sponges; however, an extremely small fraction of the sponge microbiome is amenable to cultivation. We took advantage of community genome assembly and binning to investigate the uncultured majority of sponge symbionts. We identified a complete N-acyl-homoserine lactone (AHL)-QS system (designated TswIR) and seven partial luxI homologues in the microbiome of Theonella swinhoei. The TswIR system was novel and shown to be associated with an alphaproteobacterium of the order Rhodobacterales, here termed Rhodobacterales bacterium TS309. The tswI gene, when expressed in Escherichia coli, produced three AHLs, two of which were also identified in a T. swinhoei sponge extract. The taxonomic affiliation of the 16S rRNA of Rhodobacterales bacterium TS309 to a sponge-coral specific clade, its enrichment in sponge versus seawater and marine sediment samples, and the presence of sponge-specific features, such as ankyrin-like domains and tetratricopeptide repeats, indicate a likely symbiotic nature of this bacterium.

Quantitative developmental transcriptomes of the Mediterranean sea urchin Paracentrotus lividus.

Embryonic development progresses through the timely activation of thousands of differentially activated genes. Quantitative developmental transcriptomes provide the means to relate global patterns of differentially expressed genes to the emerging body plans they generate. The sea urchin is one of the classic model systems for embryogenesis and the models of its developmental gene regulatory networks are of the most comprehensive of their kind. Thus, the sea urchin embryo is an excellent system for studies of its global developmental transcriptional profiles. Here we produced quantitative developmental transcriptomes of the sea urchin Paracentrotus lividus (P. lividus) at seven developmental stages from the fertilized egg to prism stage. We generated de-novo reference transcriptome and identified 29,817 genes that are expressed at this time period. We annotated and quantified gene expression at the different developmental stages and confirmed the reliability of the expression profiles by QPCR measurement of a subset of genes. The progression of embryo development is reflected in the observed global expression patterns and in our principle component analysis. Our study illuminates the rich patterns of gene expression that participate in sea urchin embryogenesis and provide an essential resource for further studies of the dynamic expression of P. lividus genes.

The making of an embryo in a basal metazoan: Proteomic analysis in the sea anemone Nematostella vectensis

Cnidarians are widely distributed basal metazoans that play an important role in the marine ecosystem. Their genetic diversity and dispersal depends on successful oogenesis, fertilization and embryogenesis. To understand the processes that lead to successful embryogenesis in these basal organisms, we conducted comparative proteomics on the model sea anemone Nematostella vectensis. We examined four developmental stages from oocyte maturation through early embryogenesis, as well as the oocyte jelly sac in which fertilization and embryogenesis take place. Our analysis revealed 37 stage‐specifically expressed proteins, including cell cycle, cellular energy related and DNA replication proteins and transcription regulators. Using in situ hybridization, we show that within the mesenteria, two cell types support successful oocyte development and embryogenesis. Large somatic supporting cells synthesize vitellogenin, the most abundant egg yolk protein within the oocyte, whereas mesenteria gland cells synthesize mucin 5B, which was found to be the main component of the jelly sac. These findings shed light on the sexual reproduction program in cnidarians and suggest a high conservation with proteins governing oogenesis in Bilateria.

Corrigendum: Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax

Corrigendum: Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax

Erratum: Corrigendum: Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax

Corrigendum: Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax

A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations

BackgroundAdenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats. In parallel, we assessed changes in ADARs expression levels.ResultsIn agreement with previous studies, we found editing to be generally higher in adult compared to neonatal rat brain. At birth, editing was generally lower in prefrontal cortex than in amygdala. Stress affected editing at the serotonin receptor 2c (Htr2c), and editing at this site was significantly altered in offspring of rats exposed to prereproductive stress across two generations. Stress-induced changes in Htr2c editing measured with mmPCR-seq were comparable to changes measured with Sanger and Illumina sequencing. Developmental and stress-induced changes in Adar and Adarb1 mRNA expression were observed but did not correlate with editing changes.ConclusionsOur findings indicate that mmPCR-seq can accurately detect A-to-I RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Our findings also point to stress in adolescence as an environmental factor that alters RNA editing patterns several generations forward, joining a growing body of literature describing the transgenerational effects of stress.

Parallel embryonic transcriptional programs evolve under distinct constraints and may enable morphological conservation amidst adaptation

Embryonic development evolves by balancing stringent morphological constraints with genetic and environmental variation. The design principle that allows developmental transcriptional programs to conserve embryonic morphology while adapting to environmental changes is still not fully understood. To address this fundamental challenge, we compare developmental transcriptomes of two sea urchin species, Paracentrotus lividus and Strongylocentrotus purpuratus, that shared a common ancestor about 40 million years ago and are geographically distant yet show similar morphology. We find that both developmental and housekeeping genes show highly dynamic and strongly conserved temporal expression patterns. The expression of other gene sets, including homeostasis and response genes, show divergent expression which could result from either evolutionary drift or adaptation to local environmental conditions. The interspecies correlations of developmental gene expressions are highest between morphologically similar developmental time points whereas the interspecies correlations of housekeeping gene expression are high between all the late zygotic time points. Relatedly, the position of the phylotypic stage varies between these two groups of genes: developmental gene expression shows highest conservation at mid-developmental stage, in agreement with the hourglass model while the conservation of housekeeping genes keeps increasing with developmental time. When all genes are combined, the relationship between conservation of gene expression and morphological similarity is partially masked by housekeeping genes and genes with diverged expression. Our study illustrates various transcriptional programs that coexist in the developing embryo and evolve under different constraints. Apparently, morphological constraints underlie the conservation of developmental gene expression while embryonic fitness requires the conservation of housekeeping gene expression and the species-specific adjustments of homeostasis gene expression. The distinct evolutionary forces acting on these transcriptional programs enable the conservation of similar body plans while allowing adaption.