Search

Conserved Non-coding Elements (CNE) in vertebrates are enriched around transcription factor loci associated with development, often participating in their regulation. However, loss and rapid divergence of CNEs has been reported in teleost fish, albeit taking only few genomes into consideration. Taking advantage of the vast increase in high-quality teleost genomes, we focus on identifying and studying the evolution of teleost CNEs. We carry out targeted genomic alignments and comparisons within the teleost phylogeny to detect CNEs and reconstruct the ancestral teleost CNE repertoire. Through this teleost-centric approach, not only do we confirm previous observations of extensive vertebrate CNE loss early in teleost evolution, but we also report massive CNE gain in the teleost stem-group over 300 million years ago. While kept vertebrate CNEs have signatures of slower evolution compared to newly gained CNEs, both groups of elements share highly similar characteristics. Using synteny-based gene association to link CNEs to putative targets, we show that the majority of teleost gained CNEs are found in the vicinity of orthologous loci involved in transcriptional regulation and embryonic development that are also associated with ancestral CNEs in other vertebrates. Moreover, teleost and vertebrate CNEs share a highly similar transcription factor binding site vocabulary dominated by homeobox, FOX, EST-related and bHLH binding motifs. Based on these data we suggest that early teleost CNE gains may reflect a restructuring of the ancestral CNE repertoire through both extreme divergence and de-novo emergence. Finally, we also show that newly identified pan-teleost CNEs have potential for accurate resolution of teleost phylogenetic placements in par with coding sequences, unlike ancestral only elements shared with spotted gar. Overall, this work provides new insight into CNE evolution, while offering a set of conserved putative regulatory elements with great value for follow-up work on phylogenomics, comparative genomics and the study of gene regulation evolution in teleosts.

SUMMARYNeural stem cell (NSC) proliferation and differentiation in the mammalian brain decreases to minimal levels postnatally. Nevertheless, neurogenic niches persist in the adult cortex and hippocampus in rodents, primates and humans, with adult NSC differentiation sharing key regulatory mechanisms with development. Adult neurogenesis impairments have been linked to Alzheimer’s Disease (AD) pathology. Addressing these impairments is a promising new avenue for therapeutic intervention based on neurogenesis. However, this possibility has been hindered by technical difficulties of using in-vivo models to conduct screens, including working with scarce NSCs in the adult brain and differences between human and mouse models or ethical limitations. In our study, we use a combination of mouse and human stem cell models to circumvent these issues and perform comprehensive characterization of a novel neurogenic compound usingin vitroscreening. Our work focuses on the brain-derived neurotrophic factor (BDNF) pathway, a pivotal neurotrophin in the regulation of neuronal growth and differentiation via its receptor tyrosine receptor kinase B (TrkB). We describe the design, chemical synthesis and biological characterization of ENT-A011, a steroidal dehydroepiandrosterone (DHEA) derivative and BDNF mimetic with neuroprotective and neurogenic actions. The compound is able to increase proliferation of mouse primary adult hippocampal NSCs and embryonic cortical NSCs, in the absence of EGF/FGF, while reducing Amyloid-β (Aβ) induced cell death, acting specifically through TrkB activation. The compound is also able to increase astrocytic gene markers involved in NSC maintenance, protect hippocampal neurons from Αβ toxicity and prevent synapse loss after Aβ treatment. To provide a translational link to human cells, we also used neural progenitor cells (NPCs) differentiated from three human induced pluripotent stem cell lines from healthy and AD donors. Our findings suggest that ENT-A011 successfully induces proliferation and prevents cell death after Aβ toxicity of human NPCs. Additionally, using RNAseq profiling, we demonstrate that the compound acts through a core gene network shared with BDNF. Our work characterizes a novel synthetic BDNF mimetic with potential neurogenic and neuroprotective actions in Alzheimer’s disease via stem cell-based screening, demonstrating the promise of stem cell systems for short-listing competitive candidates for further testing.

Devil firefish (Pterois miles), a member of Scorpaenidae family, is one of the most successful marine non-native species, dominating around the world, that was rapidly spread into the Mediterranean Sea, through the Suez Canal, originating from the Indian Ocean. Even though lionfishes (Scorpaenidae) are identified among the most prosperous marine invaders, within this taxonomic group, the genomic resources are scant, while reference genome assemblies are totally absent. Here, we built and analyzed the first reference genome assembly ofP. milesand explored its evolutionary background. The resulting genome assembly consisted of 660 contigs and scaffolds (N50 = 14,5 Mb) with a total size of about 902 Mb, while delivering 98% BUSCO completeness. We identified and described the large amount of transposable elements present in the genome and based on genomic data we constructed the first teleost phylogeny which includes a member of genusPterois. The high-quality and contiguityde novogenome assembly built herein provides a valuable resource for future studies in species’ biology and ecology, lionfish phylogeny, the influence of transposable elements on the evolution of vertebrate genomes and fish toxins evolution.

The meagre, Argyrosomus regius, has recently become a species of increasing economic interest for the Mediterranean aquaculture and there is ongoing work to boost production efficiency through selective breeding. Access to the complete genomic sequence will provide an essential resource for studying quantitative trait-associated loci and exploring the genetic diversity of different wild populations and aquaculture stocks in more detail. Here, we present the first complete genome for A. regius, produced through a combination of long and short read technologies and an efficient in-house developed pipeline for assembly and polishing. Scaffolding using previous linkage map data allowed us to reconstruct a chromosome level assembly with high completeness, complemented with gene annotation and repeat masking. We use this new resource to study the evolution of the meagre genome and other Sciaenids, via a comparative analysis of 25 high-quality teleost genomes. Combining a rigorous investigation of gene duplications with base-wise conservation analysis, we identify candidate loci related to immune, fat metabolism and growth adaptations in the meagre. Following phylogenomic reconstruction, we show highly conserved synteny within Sciaenidae. In contrast, we report rapidly evolving syntenic rearrangements and gene copy changes in the sex-related dmrt1 neighbourhood in meagre and other members of the family. These novel genomic datasets and findings will add important new tools for aquaculture studies and greatly facilitate husbandry and breeding work in the species.

The evolutionary origin of vertebrates included innovations in sensory processing associated with the acquisition of a predatory lifestyle. Vertebrates perceive external stimuli through sensory systems serviced by cranial sensory ganglia, whose neurons arise predominantly from cranial placodes; however, the understanding of the evolutionary origin of placodes and cranial sensory ganglia is hampered by the anatomical differences between living lineages and the difficulty in assigning homology between cell types and structures. Here we show that the homeobox transcription factor Hmx is a constitutive component of vertebrate sensory ganglion development and that in the tunicate Ciona intestinalis, Hmx is necessary and sufficient to drive the differentiation programme of bipolar tail neurons, cells previously thought to be homologues of neural crest. Using Ciona and lamprey transgenesis, we demonstrate that a unique, tandemly duplicated enhancer pair regulated Hmx expression in the stem-vertebrate lineage. We also show notably robust vertebrate Hmx enhancer function in Ciona, demonstrating that deep conservation of the upstream regulatory network spans the evolutionary origin of vertebrates. These experiments demonstrate regulatory and functional conservation between Ciona and vertebrate Hmx, and point to bipolar tail neurons as homologues of cranial sensory ganglia.

Exploring the genetic background of successful invasive phenotypes is essential in understanding their underlying mechanisms. Lionfish (Scorpaenidae) are identified among the most prosperous invaders spread along the coastlines of the Atlantic and recently the Mediterranean Sea. However, within this family, the genomic resources are depauperate while reference genome assemblies are totally absent. In this study, we focus on the devil firefish, Pterois miles (Bennett, 1828), one of the most successful invasive species across the coasts of the Mediterranean Sea. We sequenced the genome of P. miles using Oxford Nanopore Technology (ONT) and Illumina reads for building the reference genome. The resulting assembly consisted of 660 contigs and scaffolds (N50 = 14,5 Mb) with a total size of about 902 Mb, while delivering 98% BUSCO completeness. The high-quality de novo genome assembly constructed here is the first one among the members of Scorpaenidae and establishes the outset for further exploring this family and the biology of venomous and invasive species.

The Tetraodontidae family encompasses several species which attract scientific interest in terms of their ecology and evolution. The silver-cheeked toadfish (Lagocephalus sceleratus) is a well-known “invasive sprinter” that has invaded and spread, in less than a decade, throughout the Eastern and part of the Western Mediterranean Sea from the Red Sea through the Suez Canal. In this study, we built and analysed the first near-chromosome level genome assembly of L. sceleratus and explored its evolutionary landscape. Through a phylogenomic analysis, we positioned L. sceleratus closer to T. nigroviridis, compared to other members of the family, while gene family evolution analysis revealed that genes associated with the immune response have experienced rapid expansion, providing a genetic basis for studying how L. sceleratus is able to achieve highly successful colonisation. Moreover, we found that voltage-gated sodium channel (NaV 1.4) mutations previously connected to tetrodotoxin resistance in other pufferfishes are not found in L. sceleratus, highlighting the complex evolution of this trait. The high-quality genome assembly built here is expected to set the ground for future studies on the species biology.

High-performance computing (HPC) systems have become indispensable for modern marine research, providing support to an increasing number and diversity of users. Pairing with the impetus offered by high-throughput methods to key areas such as non-model organism studies, their operation continuously evolves to meet the corresponding computational challenges. Here, we present a Tier 2 (regional) HPC facility, operating for over a decade at the Institute of Marine Biology, Biotechnology, and Aquaculture of the Hellenic Centre for Marine Research in Greece. Strategic choices made in design and upgrades aimed to strike a balance between depth (the need for a few high-memory nodes) and breadth (a number of slimmer nodes), as dictated by the idiosyncrasy of the supported research. Qualitative computational requirement analysis of the latter revealed the diversity of marine fields, methods, and approaches adopted to translate data into knowledge. In addition, hardware and software architectures, usage statistics, policy, and user management aspects of the facility are presented. Drawing upon the last decade’s experience from the different levels of operation of the Institute of Marine Biology, Biotechnology, and Aquaculture HPC facility, a number of lessons are presented; these have contributed to the facility’s future directions in light of emerging distribution technologies (e.g., containers) and Research Infrastructure evolution. In combination with detailed knowledge of the facility usage and its upcoming upgrade, future collaborations in marine research and beyond are envisioned.

This preprint introduces key pieces of information of the IMBBC HPC facility regarding its history, usage statistics, user management and in-house developed containers/workflows along with accompanying data. It also intends to share them to the rest of the scientific community either directly as a data-presenting paper or by accompanying sister publications (where data interpretations and conclusions are given)., HZ and NG contributed equally at this work. Correspondence to: E. Pafilis; pafilis@hcmr.gr