Biology subjects

Papadogiannis, V.

Publications and source records attributed to Papadogiannis, V..

6 recordsLinked to original sources

bioRxiv2026

The epigenomic landscape of deep lineage divergence: The case of the European sea bass

BackgroundUnderstanding the role of non-coding genomic variation in speciation remains a major challenge in evolutionary biology. Here, we investigated whether regulatory elements contribute to this process between Atlantic and Mediterranean lineages of European sea bass (Dicentrarchus labrax), a well-characterized case-study near speciation where barriers to introgression exist in the presence of connectivity between diverging populations. ResultsWe generated a novel, highly contiguous genome assembly, which was annotated at the epigenomic level using ATAC-seq and ChIP-seq with six embryonic developmental stages and five tissue types in adult fish, identifying thousands of promoters, enhancers, and open chromatin regions. Integrating this annotation with whole-genome sequence data from 65 individuals across three geographically distinct populations, we identified 57,505 outlier SNPs and 332 structural variants (SVs) showing elevated differentiation between Atlantic and East Mediterranean lineages. Outlier SVs affected key regulatory elements and coding genes, while outlier SNPs were enriched in regulatory elements, particularly enhancers active in adult tissues. Local genomic divergence correlated positively with regulatory element density, especially on chromosomes 1, 9, and 18, which are enriched in genes related to osmoregulation, immune response, and oxidative stress -- processes relevant to adaptation across contrasting marine environments. ConclusionsThese findings support a major role for regulatory variation in driving deep lineage divergence through local adaptation.

evolutionary biology↗

bioRxiv2023

Extensive Loss and Gain of Conserved Non-Coding Elements during Early Teleost Evolution

Conserved Non-coding Elements (CNE) in vertebrates are enriched around transcription factor loci associated with development. However, loss and rapid divergence of CNEs has been reported in teleost fish, albeit taking only few genomes into consideration. Taking advantage of the recent increase in high-quality teleost genomes, we focus on studying the evolution of teleost CNEs, carrying out targeted genomic alignments and comparisons within the teleost phylogeny to detect CNEs and reconstruct the ancestral teleost CNE repertoire. This teleost-centric approach confirms previous observations of extensive vertebrate CNE loss early in teleost evolution, but also reveals massive CNE gain in the teleost stem-group over 300 million years ago. Using synteny-based association to link CNEs to their putatively regulated target genes, we show the most teleost gained CNEs are found in the vicinity of orthologous loci involved in transcriptional regulation and embryonic development that are also associated with CNEs in other vertebrates. Moreover, teleost and vertebrate CNEs share a highly similar motif and transcription factor binding site vocabulary. We suggest that early teleost CNE gains reflect a restructuring of the ancestral CNE repertoire through both extreme divergence and de novo emergence. Finally, we support 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. This work provides new insight into CNE evolution with great value for follow-up work on phylogenomics, comparative genomics and the study of gene regulation evolution in teleosts.

genomics↗

bioRxiv2023

Comprehensive characterization of the neurogenic and neuroprotective action of a novel TrkB agonist using mouse and human stem cell models of Alzheimer's Disease

Neural 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 Alzheimers 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 using in vitro screening. 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-{beta} (A{beta}) 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 A{beta} toxicity and prevent synapse loss after A{beta} 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 A{beta} 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 Alzheimers disease via stem cell-based screening, demonstrating the promise of stem cell systems for short-listing competitive candidates for further testing.

pharmacology and toxicology↗

bioRxiv2023

Near-chromosome level genome assembly of devil firefish, Pterois miles

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 of P. miles and 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 genus Pterois. The high-quality and contiguity de novo genome 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.

genomics↗

bioRxiv2022

Chromosome assembly for the meagre, Argyrosomus regius, reveals species adaptations and sciaenid sex-related locus 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.

genomics↗

bioRxiv2020

Hmx gene conservation identifies the evolutionary origin of vertebrate cranial ganglia

The evolutionary origin of vertebrates included innovations in sensory processing associated with the acquisition of a predatory lifestyle1. Vertebrates perceive external stimuli through sensory systems serviced by cranial sensory ganglia (CSG) which develop from cranial placodes; however understanding the evolutionary origin of placodes and CSGs is hampered by the gulf between living lineages and difficulty in assigning homology between cell types and structures. Here we use the Hmx gene family to address this question. We show Hmx is a constitutive component of vertebrate CSG development and that Hmx in the tunicate Ciona is able to drive the differentiation program of Bipolar Tail Neurons (BTNs), cells previously thought neural crest homologs2,3. Using Ciona and lamprey transgenesis we demonstrate that a unique, tandemly duplicated enhancer pair regulated Hmx in the stem-vertebrate lineage. Strikingly, we also show 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 confirm BTNs as CSG homologs. Our analysis also identifies derived evolutionary changes, including a genetic basis for secondary simplicity in Ciona and unique regulatory complexity in vertebrates.

evolutionary biology↗