Biology subjects

Wood, J.

Publications and source records attributed to Wood, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Tail length of triazine-based lipids influences blood clotting risk in vitro and in vivo

Lung-targeted delivery of mRNA with lipid nanoparticles (LNPs) demonstrates high potential for therapeutic applications in pulmonary disorders. However, progress in pulmonary mRNA therapeutics is constrained by the challenges of engineering lipids that are both safe and highly effective at targeting the lungs. To meet these critical needs, we designed triazine-based (TZ) ionizable lipids with cyanuric chloride as the linker between the cationic head and the lipophilic tail, which allows for easy derivatization capable of systemic mRNA delivery. Three TZ-based lipids were synthesized using the same ionizable headgroups while differing in the carbon tail length and evaluated for their in vitro and in vivo protein expression. Notably, all three lipids result in pulmonary expression after intravenous administration, but the TZ lipid containing a C14 tail does so without any indication of thrombosis, both in vitro and in vivo as compared to other formulations. Our findings highlight the effect of minor chemical modifications driving altered in vivo activity, thus enabling new opportunities for safe pulmonary delivery of mRNA for lung-related diseases.

bioengineering↗

bioRxiv2026

Individual limb measures of split-belt adaptation are correlated with shifts in lower limb position sense

Stable gait in humans relies on both precise estimates of lower limb position and the ability to robustly adapt walking movements across different environments. However, the specific relationship between sensorimotor adaptation and the perception of lower limb position during gait remains unclear. In this study, we tested a specific theoretical model of how sensorimotor adaptation during gait could cause a shift in the perception of lower limb position. To test this theory, we probed lower limb position sense estimates using a valid and reliable two-alternative forced choice task before and after a long bout of split-belt treadmill walking. The theoretical model assumes that a shift in the perception of limb position is caused by the optimal integration between the predicted and actual sensory feedback of step lengths. Using this model, we generated hypotheses relating to the direction of the shift in limb position sense estimates as well as the relationship between the magnitude of these sensory shifts and the plateau of adaptation when measured using the canonical step length asymmetry index. Like prior studies, participants robustly adapted their step length asymmetry during split-belt treadmill walking. However, we did not observe reliable changes in limb position sense after this adaptation relative to baseline. Furthermore, the changes in limb position sense were not related to the plateau of sensorimotor adaptation. However, post-hoc analysis of other gait parameters, most notably double limb support time, revealed a strong relationship between its adaptation plateau and sensory recalibration. These results suggest that while the specific theorical model we proposed was not supported, sensory recalibration could play an important role in split-belt adaptation and raise questions regarding the error signal driving split-belt adaptation.

neuroscience↗

bioRxiv2026

Hybridisation and herbivory fuel Amazonian tree radiations

Tropical rainforests, and Amazonia in particular, contain more tree species than anywhere else, most of which arose through rapid evolutionary radiations 1-3. Rapid radiations are often catalysed by ecological opportunity 4-6, which in rainforest trees is presented by intense insect herbivore pressure, spurring the evolution of novel plant defence chemistry to escape it 7. However, we do not understand how long-lived trees can adapt quickly enough to keep pace with rapidly-evolving insect herbivores. Here we show that hybridisation in rainforest trees, which was considered rare, allows exchange of gene clusters used in chemical defence against herbivore attack, facilitating rapid adaptation and diversification. Using genome sequencing for 461 individuals from the genus Inga, a characteristic Amazonian tree radiation, we find that regional tree communities form syngameons - networks of closely related, co-occurring species connected by gene flow. Integrating these genomes with herbivore abundance data from the same communities across the tropical Americas, we show that herbivore compositional turnover coincides with local, recurrent interspecific transfer of defence gene clusters that are retained by balancing selection, consistent with fluctuating selective pressure imposed by shifting herbivore communities. Together, our results demonstrate that hybridisation allows long-lived tropical trees to rapidly evolve chemical defences, fuelling adaptation to the relentless insect herbivory that structures the worlds most species-rich forests.

evolutionary biology↗

bioRxiv2026

Synthetic analogue of adrenocorticotropic hormone, ACTH(4-7)PGP delays neurological manifestations in diseases of mucopolysaccharidosis III spectrum by reducing neuroinflammation and rescuing neurotransmission, synaptogenesis, and axonal demyelination

Mucopolysaccharidosis III (MPS III or Sanfilippo disease) is a spectrum of 4 genetic disorders (MPS IIIA-D), caused by defects in the genes SGSH, NAGLU, HGSNAT and GNS encoding enzymes involved in degradation of heparan sulfate (HS). HS accumulates in brain tissues and causes neuronal dysfunction and neurodegeneration leading to neuropsychiatric problems, developmental delays, childhood dementia, blindness and death during the second decade of life. Previously, we demonstrated that pathophysiological mechanisms, underlying MPS IIIC in mouse models, involves functional pathological changes, affecting synaptogenesis and synaptic transmission and leading to learning and memory deficits. These results suggested that a treatment for MPS III could be developed by using compounds inducing synaptogenesis. In the current study, we tested the efficacy of a synthetic peptide ACTH(4-7)PGP, an analog of adrenocorticotropic hormone fragment, previously used as a neuroprotective and anti-inflammatory medication for treatment of acute neurological conditions, including stroke. We show that intranasal administration of ACTH(4-7)PGP restores defective synaptic transmission in CA1 pyramidal neurons of MPS IIIA and MPS IIIC mouse models and rescues the decrease in synaptic proteins in cultured MPS IIIC mouse hippocampal neurons and iPSC-derived neurons of human MPS IIIA, MPS IIIB and MPS IIIC patients. Furthermore, daily intranasal administration of ACTH(4-7)PGP to MPS IIIC and MPS IIIA mice reduces hyperactivity and rescues defects in working and spatial memory, delays progression of CNS pathology including neuroinflammation and axonal demyelination, and increases the lifespan. Together with the absence of any adverse reactions to ACTH(4-7)PGP in the MPS III and WT mice, our results justify testing the drugs efficacy in clinical settings.

genetics↗

bioRxiv2025

Gain and loss of function changes in CACNA1C affect neuronal networks through divergent pathways

BackgroundCACNA1C encodes the pore-forming subunit of the L-type calcium channel Cav1.2. Common variants in CACNA1C are associated with psychiatric disorders, while rare single-nucleotide variants cause CACNA1C-related disorder (CRD), a multi-system disorder with symptoms that include autism spectrum disorder (ASD), intellectual disability and seizures. However, the cellular mechanisms linking CACNA1C dysfunction to neurodevelopmental phenotypes remain poorly understood. MethodsWe generated isogenic CACNA1C loss-of-function (LoF) induced pluripotent stem cell (iPSC) lines and reprogrammed a line from an individual carrying a novel gain-of-function (GoF) variant in CACNA1C. Neuronal activity was assessed using multi-electrode arrays (MEA), pharmacological manipulation, and gene expression analysis. Early developmental phenotypes were examined using qRT-PCR, immunocytochemistry, and RNA sequencing. ResultsLoF and GoF patient-derived neurons displayed opposing alterations in network dynamics. Pharmacological and molecular assays indicated that these network differences were associated with dysregulated GABAergic signalling. Early developmental analysis revealed that loss of CACNA1C altered rosette morphology, CREB phosphorylation, and transcriptional programs related to axonogenesis and synaptic signalling, indicating effects on neuronal differentiation. The patient line exhibited opposing phenotypes, reflecting variant-specific effects. ConclusionsThese findings demonstrate that Cav1.2 regulates excitatory-inhibitory balance, network organization, and aspects of neurodevelopment. Divergent effects of LoF and GoF variants highlight how altered Cav1.2 signalling contributes to variable neurodevelopmental phenotypes, including ASD and epilepsy, and establish a framework for defining CACNA1C variant effects in human neurons.

neuroscience↗

bioRxiv2025

Inter-Instrument Quantification of Fluorescence Read-out Signal Using DNA Origami Calibrator Beads

Comparing experimental results across different instruments and laboratories is challenging due to variations in instrument sensitivity and resolution, particularly for analyzing nano-sized and dimly fluorescing particles like viruses and extracellular vesicles. To address this challenge, we conducted a study using fluorescent DNA calibrator beads to test, calibrate, and compare the sensitivity of five different flow cytometers. Our approach involves DNA beads produced through a bottom-up DNA origami method. These beads contain a defined number of fluorophores (0-220) and exhibit no autofluorescence. Fluorophores are precisely conjugated onto the beads in a controlled array, minimizing dye interactions. This allows triggering on one fluorophore and calibration based on another, facilitating precise and accurate calibration in absolute fluorophore numbers. We tested five flow cytometers--FACSAria III, NovoCyte 3000YBG, NovoCyte Quanteon 4500, LSRFortessa, and CytoFlex S--using Cy5 and FAM DNA calibrator beads. We investigated various instrument parameters, including count rate, trigger and calibration gain, gain amplification linearity, and fluorescence trigger sensitivity. Using fluorescent triggering, we demonstrated the capability to detect dimly fluorescent particles, enabling instrument calibration and fluorescence sensitivity comparison using DNA calibrators. In conclusion, our study offers a robust method for addressing instrument fluorescence channel resolution in absolute fluorophore numbers in the analysis of nano-sized and dimly fluorescent particles.

biophysics↗

bioRxiv2025

Genomic and genetic insights into speciation and pigment pattern diversification in Danio fishes

The Danioninae subfamily of teleost fishes boasts up to four hundred distinct species that have evolved to display a stunning diversity of morphological forms. Here we use newly assembled genome sequences of four laboratory and wild zebrafish strains as well as eleven species of the Danio and Danionella genera to explore their phylogenetic history and the genetic basis of pigment pattern diversification. Phylogenomic analyses uncover extensive introgression and incomplete lineage sorting that have obscured phylogenetic relationships within Danio and corroborate an ancient hybrid origin of zebrafish. Whereas D. rerio inherited ancestral horizontal stripes, relatives repeatedly evolved spots and vertical bars. Interspecific complementation tests reveal functional divergence of the adhesion molecule gene igsf11 and the gap junction gene gja5b between the striped zebrafish and Danio species with divergent patterns. Comparative genomic and transcriptomic analyses suggest that protein and regulatory evolution have accompanied pigment pattern diversification. Our analyses elucidate complex genetic changes underlying the phylogenetic history and morphological diversification in the Danio genus. Resolved phylogenetic relationships, available genome assemblies, transcriptomes, and genetic tractability establish Danio fish species as excellent models for biomedical research in vertebrates.

genomics↗

bioRxiv2025

Spatially Resolved Microglial Expression Around Aβ Plaques in Human Alzheimers Disease Tissue

Using microglia-enriched spatial transcriptomics on human Alzheimers disease tissue, we identify distinct gene expression changes across microglia located in direct contact with plaques, in periplaque regions, and in areas distant from plaques. We define a group of plaque contact-only microglial (PCOM) genes whose expression increases exclusively in microglia directly contacting plaques. These genes show significant overlap with previously reported gene sets, suggesting that many of the well-characterised disease-associated microglia (DAM) and other AD-related gene-expression signatures are only upregulated when microglia contact plaques. We further identify distinct co-expression networks associated with disease-relevant covariates, including an immune module linked to APOE genotype and a synaptic-mitochondrial module negatively associated with Braak stage. Finally, we compare the human dataset to our previously published data from 18-month-old AppNL-F mice, generated using the same experimental paradigm and demonstrate cross-species concordance in gene expression particularly within plaque-contacting microglia.

neuroscience↗

bioRxiv2025

The Microglial Trem2 R47H Alzheimer's Disease Risk Variant Impairs Early Hippocampal Synaptic Remodeling

The rare R47H variant of the microglial TREM2 gene increases Alzheimers disease (AD) risk, but its effects on early hippocampal circuitry remain unclear. Trem2 has been reported to be important for microglial-dependent refinement of excitatory synaptic circuits in development. We hypothesized that loss of TREM2 function might result in changes in circuitry due to reduced microglial ability to prune inactive synapses and that this could predispose individuals to later disease. We compared basal synaptic transmission and synaptic density in 3-week-old WT and homozygous Trem2 R47H knockin mice, using in vitro patch clamp recordings and Bassoon-Homer1 immunohistochemistry. Basal synaptic activity, miniature excitatory events, and evoked release probability were unchanged. Synapse density in CA1 and CA3 showed substantial between-mouse variability but no evidence of genotype or regional differences. This variable CA1 synapse density was positively correlated with CA1 miniature excitatory event frequency. Although between-mouse variability in synaptic density could mask subtle changes, these data indicate that early effects of Trem2 R47H in these mice are not sufficient to produce a consistent change in early postnatal hippocampal excitatory synapse density or basal synaptic transmission under these conditions. This supports the view that TREM2-linked AD risk may act primarily through context-dependent mechanisms that become relevant with ageing, neuroinflammatory challenge, or AD pathology.

neuroscience↗

bioRxiv2024

Chromosome-scale genome assembly and de novo annotation of Alopecurus aequalis.

Alopecurus aequalis is a winter annual or short-lived perennial bunchgrass which has in recent years emerged as the dominant agricultural weed of barley and wheat in certain regions of China and Japan, causing significant yield losses. Its robust tillering capacity and high fecundity, combined with the development of both target and non-target-site resistance to herbicides means it is a formidable challenge to food security. Here we report on a chromosome-scale assembly of A. aequalis with a genome size of 2.83 Gb. The genome contained 33,758 high-confidence protein-coding genes with functional annotation. Comparative genomics revealed that the genome structure of A. aequalis is more similar to Hordeum vulgare rather than the more closely related Alopecurus myosuroides and has undergone an expansion of cytochrome P450 genes, a gene family involved in non-target-site herbicide resistance.

plant biology↗

bioRxiv2024

Cell-intrinsic platinum response and associated genetic and gene expression signatures in ovarian cancer cell lines and isogenic models

Ovarian cancers are still largely treated with platinum-based chemotherapy as the standard of care, yet few biomarkers of clinical response have had an impact on clinical decision making as of yet. Two particular challenges faced in mechanistically deciphering platinum responsiveness in ovarian cancer have been the suitability of cell line models for ovarian cancer subtypes and the availability of information on comparatively how sensitive ovarian cancer cell lines are to platinum. We performed one of the most comprehensive profiles to date on 36 ovarian cancer cell lines across over seven subtypes and integrated drug response and multiomic data to improve on our understanding of the best cell line models for platinum responsiveness in ovarian cancer. RNA-seq analysis of the 36 cell lines in a single batch experiment largely conforms with the currently accepted subtyping of ovarian cancers, further supporting other studies that have reclassified cell lines and demonstrate that commonly used cell lines are poor models of high-grade serous ovarian carcinoma. We performed drug dose response assays in the 32 of these cell lines for cisplatin and carboplatin, providing a quantitative database of IC50s for these drugs. Our results demonstrate that cell lines largely fall either well above or below the equivalent dose of the clinical maximally achievable dose (Cmax) of each compound, allowing designation of cell lines as sensitive or resistant. We performed differential expression analysis for high-grade serous ovarian carcinoma cell lines to identify gene expression correlating with platinum-response. Further, we generated two platinum-resistant derivatives each for OVCAR3 and OVCAR4, as well as leveraged clinically-resistant PEO1/PEO4/PEO6 and PEA1/PEA2 isogenic models to perform differential expression analysis for seven total isogenic pairs of platinum resistant cell lines. While gene expression changes overall were heterogeneous and vast, common themes were innate immunity/STAT activation, epithelial to mesenchymal transition and stemness, and platinum influx/efflux regulators. In addition to gene expression analyses, we performed copy number signature analysis and orthogonal measures of homologous recombination deficiency (HRD) scar scores and copy number burden, which is the first report to our knowledge applying field-standard copy number signatures to ovarian cancer cell lines. We also examined markers and functional readouts of stemness that revealed that cell lines are poor models for examination of stemness contributions to platinum resistance, likely pointing to the fact that this is a transient state. Overall this study serves as a resource to determine the best cell lines to utilize for ovarian cancer research on certain subtypes and platinum response studies, as well as sparks new hypotheses for future study in ovarian cancer.

cancer biology↗

bioRxiv2024

Genomics of Neotropical biodiversity indicators: two butterfly radiations with rampant chromosomal rearrangements and hybridisation

A major question in evolutionary biology is what drives the diversification of lineages. Rapid, recent radiations are ideal systems for addressing how new species arise because they still show key morphological and ecological adaptations associated with speciation. While most studied recent radiations have evolved in an insular environment, less research has been carried out on continental radiations with complex species interactions. Melinaea and Mechanitis butterflies (Nymphalidae: Ithomiini) have rapidly radiated in the Neotropics. They are classical models for Amazonian biogeography and colour pattern mimicry and have been proposed as biodiversity indicators. We generated reference genomes for five species of each genus, and whole-genome resequencing data of most species and subspecies covering a wide geographic range to assess phylogeographic relationships, patterns of hybridisation and chromosomal rearrangements. Our data help resolve the classification of these taxonomically challenging butterflies and reveal very high diversification rates. We find rampant evidence of historical hybridisation and putative hybrid species in both radiations, which may have facilitated their rapid diversification. Moreover, dozens of chromosomal fusions and fissions were identified between congeneric species, and even some within species. We conclude that interactions between geography, hybridisation and chromosomal rearrangements have contributed to these two rapid radiations in the highly diverse Neotropical region. We suggest that rapid radiations may be spurred by repeated periods of geographic isolation during Pleistocene climate oscillations, combined with lineage-specific rapid accumulation of incompatibilities during allopatric phases, followed by secondary contact with some gene exchange. Significance StatementUnderstanding factors contributing to rapid speciation is a key aim of evolutionary biology. Here we focus on two rapid radiations of Neotropical butterflies. Our genomic data with broad taxonomic and geographic coverage reveal rampant hybridisation and chromosomal rearrangements, each likely contributing to the high diversification rates. Our study highlights the use of genomic data to resolve taxonomically challenging species groups and elucidate drivers of diversification in rapid radiations. We show that for biodiversity hotspots with recent radiations, barcoding is insufficient to characterise species richness due to gene flow and recent speciation. The taxonomic implications of both introgression and karyotype diversity for species delimitation are important to consider during monitoring and management of biodiversity in these vulnerable habitats.

evolutionary biology↗

bioRxiv2024

Chemical imaging signatures delineate heterogeneous amyloid plaque populations across the Alzheimers disease spectrum

Amyloid plaque deposition is recognized as the primary pathological hallmark of Alzheimers disease(AD) that precedes other pathological events and cognitive symptoms. Plaque pathology represents itself with an immense polymorphic variety comprising plaques with different stages of amyloid fibrillization ranging from diffuse to fibrillar, mature plaques. The association of polymorphic A{beta} plaque pathology with AD pathogenesis, clinical symptoms and disease progression remains unclear. Advanced chemical imaging tools, such as functional amyloid microscopy combined with MALDI mass spectrometry imaging (MSI), are now enhanced by deep learning algorithms. This integration allows for precise delineation of polymorphic plaque structures and detailed identification of their associated A{beta} compositions. We here set out to make use of these tools to interrogate heterogenic plaque types and their associated biochemical architecture. Our findings reveal distinct A{beta} signatures that differentiate diffuse plaques from fibrilized ones, with the latter showing substantially higher levels of A{beta}x-40. Notably, within the fibrilized category, we identified a distinct subtype known as coarse-grain plaques. Both in sAD and fAD brain tissue, coarse grain plaques contained more A{beta}x-40 and less A{beta}x-42 compared with cored plaques. The coarse grain plaques in both sAD and fAD also showed higher levels of neuritic content including paired helical filaments (PHF-1)/phosphorylated phospho Tau-immunopositive neurites. Finally, the A{beta} peptide content in coarse grain plaques resembled that of vascular A{beta} deposits (CAA) though with relatively higher levels of A{beta}1-42 and pyroglutamated A{beta}x-40 and A{beta}x-42 species in coarse grain plaques. This is the first of its kind study on spatial in situ biochemical characterization of different plaque morphotypes demonstrating the potential of the correlative imaging techniques used that further increase the understanding of heterogeneous AD pathology. Linking the biochemical characteristics of amyloid plaque polymorphisms with various AD etiologies and toxicity mechanisms is crucial. Understanding the connection between plaque structure and disease pathogenesis can enhance our insights. This knowledge is particularly valuable for developing and advancing novel, amyloid-targeting therapeutics.

neuroscience↗

bioRxiv2024

Novel therapies for cancer-induced bone pain

1.Cancer pain is a growing problem, especially with the substantial increase in cancer survival. Reports indicate that bone metastasis, whose primary symptom is bone pain, occurs in 65-75% of patients with advanced breast or prostate cancer. We optimized a preclinical in vivo model of cancer-induced bone pain (CIBP) involving the injection of Lewis Lung Carcinoma cells into the intramedullary space of the femur of C57BL/6 mice or transgenic mice on a C57BL/6 background. Mice gradually reduce the use of the affected limb, leading to altered weight bearing. Symptoms of secondary cutaneous heat sensitivity also manifest themselves. Following optimization, three potential analgesic treatments were assessed; 1) single ion channel targets (targeting the voltage-gated sodium channels NaV1.7, NaV1.8, or acid-sensing ion channels), 2) silencing {micro}-opioid receptor-expressing neurons by modified botulinum compounds, and 3) targeting two inflammatory mediators simultaneously (nerve growth factor (NGF) and tumor necrosis factor (TNF)). Unlike global NaV1.8 knockout mice which do not show any reduction in CIBP-related behavior, embryonic conditional NaV1.7 knockout mice in sensory neurons exhibit a mild reduction in CIBP-linked behavior. Modified botulinum compounds also failed to cause a detectable analgesic effect. In contrast, inhibition of NGF and/or TNF resulted in a significant reduction in CIBP-driven weight-bearing alterations and prevented the development of secondary cutaneous heat hyperalgesia. Our results support the inhibition of these inflammatory mediators; and more strongly their dual inhibition to treat CIBP, given the superiority of combination therapies in extending the time needed to reach limb use score zero in our CIBP model.

neuroscience↗

bioRxiv2024

Two distinct mechanisms for Nav1.7 null analgesia

Genetic deletion and pharmacological inhibition are distinct approaches to unravelling pain mechanisms, identifying targets and developing new analgesics. Both approaches have been applied to the voltage-gated sodium channels Nav1.7 and Nav1.8. Genetic deletion of Nav1.8 in mice leads to a loss of pain, and antagonists are effective analgesics. Complete embryonic loss of Nav1.7 in humans or in mouse sensory neurons leads to profound analgesia substantially mediated by endogenous opioid signaling, and anosmia that is opioid independent. Autonomic function appears to be normal. Adult deletion of Nav1.7 in sensory neurons also leads to analgesia with diminished sensory neuron excitability but there is no opioid component of analgesia. Pharmacological inhibition of Nav1.7 leads to dramatic side-effects on the autonomic nervous system. Here we compare and contrast the distinct embryonic and adult null mechanisms of Nav1.7 loss-of-function analgesia. We describe an endogenous opioid mechanism of analgesia that provides new opportunities for therapeutic intervention and pain relief. SummaryIn contrast to Nav1.8, Nav1.7, a genetically validated human pain target is unsuitable for small molecule drug development because of its wide spread expression both centrally and peripherally.

neuroscience↗

bioRxiv2024

Superiority of chromosomal compared to plasmid-encoded compensatory mutations

Plasmids are important vectors of horizontal gene transfer in microbial communities but can impose a burden on the bacteria that carry them. Such plasmid fitness costs are thought to arise principally from conflicts between chromosomal- and plasmid-encoded molecular machineries, and thus can be ameliorated by compensatory mutations (CMs) that reduce or resolve the underlying causes. CMs can arise on plasmids (i.e. plaCM) or on chromosomes (i.e. chrCM), with contrasting predicted effects upon plasmid success and subsequent gene transfer because plaCM can also reduce fitness costs in plasmid recipients, whereas chrCM can potentially ameliorate multiple distinct plasmids. Here, we develop theory and a novel experimental system to directly compare the ecological effects of plaCM and chrCM that arose during evolution experiments between Pseudomonas fluorescens SBW25 and its sympatric mercury resistance megaplasmid pQBR57. We show that while plaCM was predicted to succeed under a broader range of parameters in mathematical models, experimentally chrCM dominated under all conditions, including those with numerous recipients, due to a more efficacious mechanism of compensation, and advantages arising from transmission of costly plasmids to competitors (plasmid weaponisation). We show analytically the presence of a mixed Rock-Paper-Scissors regime for plaCM, driven by trade-offs with horizontal transmission, that explains the observed failure of plaCM to dominate even in competition against an uncompensated plasmid. Our results reveal broader implications of plasmid-bacterial evolution for plasmid ecology, demonstrating the importance of compensatory mutations for resistance gene spread. One consequence of the superiority of chrCM over plaCM is the likely emergence in microbial communities of compensated bacteria that can act as hubs for plasmid accumulation and dissemination.

microbiology↗

bioRxiv2023

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics

A global genome database of all of Earths species diversity could be a treasure trove of scientific discoveries. However, regardless of the major advances in genome sequencing technologies, only a tiny fraction of species have genomic information available. To contribute to a more complete planetary genomic database, scientists and institutions across the world have united under the Earth BioGenome Project (EBP), which plans to sequence and assemble high-quality reference genomes for all [~]1.5 million recognized eukaryotic species through a stepwise phased approach. As the initiative transitions into Phase II, where 150,000 species are to be sequenced in just four years, worldwide participation in the project will be fundamental to success. As the European node of the EBP, the European Reference Genome Atlas (ERGA) seeks to implement a new decentralised, accessible, equitable and inclusive model for producing high-quality reference genomes, which will inform EBP as it scales. To embark on this mission, ERGA launched a Pilot Project to establish a network across Europe to develop and test the first infrastructure of its kind for the coordinated and distributed reference genome production on 98 European eukaryotic species from sample providers across 33 European countries. Here we outline the process and challenges faced during the development of a pilot infrastructure for the production of reference genome resources, and explore the effectiveness of this approach in terms of high-quality reference genome production, considering also equity and inclusion. The outcomes and lessons learned during this pilot provide a solid foundation for ERGA while offering key learnings to other transnational and national genomic resource projects.

genomics↗

bioRxiv2023

Ancient mitogenomes reveal evidence for the late Miocene dispersal of mergansers to the Southern Hemisphere

Mergansers are riverine and coastal piscivorous ducks that are widespread throughout North America and Eurasia but uncommon in the Southern Hemisphere. One species occurs in South America and at least two extinct species from New Zealand. It has been proposed that Southern Hemisphere mergansers were founded by independent dispersal events from the Northern Hemisphere. However, some morphological and behavioural evidence suggests that Southern Hemisphere mergansers may be closely related to one another. They share several characteristics that differ from Northern Hemisphere mergansers (e.g., non-migratory vs. migratory, sexual monochromatism vs. sexual dichromatism, long vs. short pair bonds). We sequenced complete mitogenomes from the Brazilian merganser and an extinct merganser from New Zealand--the Auckland Island merganser. Our results show the Brazilian and Auckland Island mergansers form a monophyletic clade with the common merganser, and that a sister relationship between Southern Hemisphere mergansers cannot be rejected. We cannot exclude the possibility that the Brazilian and Auckland Island mergansers descend from a single dispersal event from the Northern Hemisphere at least seven million years ago. Nuclear (palaeo)genomic data may help to resolve the relationship between living and extinct mergansers, including merganser fossils from New Zealand that have not been subjected to palaeogenetic analysis.

genetics↗