Biology subjects

Jones, A.

Publications and source records attributed to Jones, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Multivalent Scaffolding by XIST E-Repeats Tunes RNA Binding Protein Cooperativity and Lowers the Phase Separation Threshold

The long-noncoding RNA XIST coordinates the random silencing of one X-chromosome in female placental mammals as a class of chromosomal dosage compensation across sexes. Critical to this process is the diffusion of XIST foci across the 155 Mb of the X-chromosome to achieve 96% repression. The E-Repeat domain on XIST primarily drives this process through the recruitment of several RNA-binding proteins, which seed condensate formation for controlled distal spreading. To date, there is a lack of biophysical characterization of interactions between the E-Repeats and its protein binding partners. Herein, we define the interaction, in vitro, between E-Repeat RNA and proteins PTBP1, ELAVL1, TDP43, and hnRNPU by applying a combination of bioinformatics, in silico characterization, and biochemical assays. We designed minimal E-Repeat RNA constructs to study the molecular mechanisms of RBP recognition and the E-Repeat ensemble. We find that all proteins sustain nanomolar interactions with single E-Repeat RNA. Through a systematic domain study, we deduce protein domain-specific RNA binding affinities, providing insight into mechanisms of E-Repeat binding. With four E-Repeats, we find that PTBP1 and ELAVL1 form higher-order assemblies and demonstrate protein competition and co-occupancy, reflecting previous in cellulo CLIP experiments. Finally, we find that PTBP1 and ELAVL1 phase separate with the four-repeat minimal constructs under minimal in vitro conditions, recapitulating the cellular behavior crucial to XIST function. All together, our findings provide mechanistic insight into the amplified impact of XIST, which at approximately 1 molecule per megabase can modulate long-range chromatin organization, illuminating another aspect of lncRNA potency, and potentially informing engineered derivatives of XIST and other lncRNAs as genetic therapeutics.

biophysics↗

bioRxiv2026

Comprehensive Phylogenomic Inference of Eucalypts Reveals Taxonomic Limits through Gene Tree Concordance

Speciation can be a slow process for long-lived organisms with large populations due to persistent incomplete lineage sorting, while hybridisation can further obscure species boundaries through admixture. In eucalypts, there is tremendous morphological and environmental variation with almost a thousand described species, subspecies, and hybrid taxa falling into multiple subgenera and intermediate sections. Multilocus molecular studies have generated concatenated species trees supporting deeper divergence between the Corymbia + Blakella + Angophora clade with the rest of eucalypts. However, the proportion of gene trees that recover the concatenated tree topology, including the taxonomic relationships among individual subgenera and sections, remains underappreciated. In this study, we assessed the predictive power of current eucalypt taxonomy - represented as a concatenated tree - in explaining topological variation across gene trees. To do this, we first extracted 1,187 BUSCO loci from short-read data of 701 samples representing roughly 500 described species using CAPTUS. We then inferred individual gene trees and a concatenated species tree using IQ-TREE2. Finally, we calculated the concordance factors for every described subgenus and section on the concatenated tree, and developed a taxonomic consistency test that tracks the taxonomic placement of each sample across gene trees. We show that, even though most taxonomic groups are monophyletic on the concatenated tree with 100% bootstrap support, several groups exhibit very low concordance, indicating that most gene trees do not recover their relationships as represented by the concatenated tree. These results highlight important considerations for current eucalypt taxonomic classification and provide a phylogenomic inference pipeline that can be applied not only to future eucalypt studies, but also to other evolutionarily complex groups of taxa.

evolutionary biology↗

bioRxiv2026

Genome assembly of Eucalyptus recurva provides insights into inbreeding and conservation priorities in Australia's rarest Eucalyptus

Eucalyptus recurva (Mongarlowe Mallee) is Critically Endangered, with only six known adult individuals persisting across two sites in the Southern Tablelands of New South Wales, Australia. Its extreme rarity, uniquely long lifespan, and limited reproductive output make it a priority for conservation genomics. Here we report the first genome assembly of E. recurva: a haplotype-resolved, gapless, telomere-to-telomere (T2T) assembly produced from Oxford Nanopore Technologies (ONT) long-read sequencing. Both haplotypes span 11 chromosomes (consistent with the conserved Eucalyptus karyotype of 2n = 22), with assembly sizes of 521.1 Mb (Hap 1) and 501.5 Mb (Hap 2), BUSCO completeness >99.6%, and quality values of >QV 62. Comparative analyses place E. recurva within section Maidenaria as sister to Eucalyptus viminalis and reveal high synteny between the two species. Inter-haplotype comparison identified 3.6 million SNPs and modest structural variation, suggesting that, despite extreme demographic bottlenecking, E. recurva retains meaningful genomic heterozygosity. We also characterise the chloroplast genome, which exhibits heteroplasmy, and report an apparently bipartite mitochondrial genome. This reference genome provides an essential resource for conservation management, population genetics, and the study of eucalypt genome evolution.

genomics↗

bioRxiv2026

Lineage-specific expansion of a potential novel class of resistance genes in Myrtaceae

Genes encoding intracellular nucleotide-binding site leucine-rich repeat (NBS-LRR) receptors represent the largest class of resistance (R) genes in plants, yet their evolutionary trajectory in trees remains poorly understood. Using high-quality long-read genome assemblies from eight Myrtaceae species, we identified 15,792 NBS-encoding genes with threefold variation in gene content across species. To investigate potential decoy domains for effector proteins of pathogens, we parsed the annotated NBS-encoding genes and determined 181 unique non-canonical domains. Notably, we observed frequent integration of Jacalin domains into TIR-NBS proteins. This novel gene family, named TNJ, is hypothesized to represent a new R gene class. Further exploration of TNJ sequence analysis shows up to seven Jacalin domains per protein and forming a monophyletic clade; however, AF3 modelling confirmed only six domains. Conserved residues in the TIR domain and functional motifs within the NB-ARC domain supports TNJs potential role in immune signalling. Most hypervariable sites and positively selected sites detected to be surface-exposed were clustered in the Jacalin region of TNJ, suggesting that surfaces of Jacalin domain may harbour residues determining pathogen recognition specificity. These findings support TNJ as a potentially new class of R genes in Myrtaceae with Jacalin as a replacement for LRR.

evolutionary biology↗

bioRxiv2026

Anthropogenic subsidies reshape Ruby-throated Hummingbird (Archilochus colubris) interactions across spatial and temporal contexts: evidence from community-collected data

O_LIRuby-throated hummingbirds (Archilochus colubris) exhibit flower preferences and readily visit human subsidies like feeders. However, foraging behavior and plant-animal interactions may vary across spatial, temporal, and landscape gradients. Despite the popularity and ubiquity of Ruby-throated Hummingbirds in the eastern U.S., there has never been a quantitative assessment of their flower preferences or feeder use across broad scales. C_LIO_LIWe investigated how feeder visitation, flower visitation, and flower trait preferences vary by latitude, season, and land use in the northeastern United States using over 6 million occurrence records of Ruby-throated Hummingbirds and flowering plants, >2,100 annotated hummingbird-flower interactions, and >2,700 feeder visit occurrences. C_LIO_LIWe found that hummingbird feeder use declined over the year, increased with latitude, and was higher in developed landscapes. Flower visitation increased over the year across all latitudes, with higher visitation in developed landscapes. Finally, we found that native plant use diverged between landscapes, such that the probability of visiting a native flower increased over time in non-developed land uses but declined over time in developed ones, demonstrating that hummingbirds track the advancement of native floral phenology and use non-native, cultivated flowers as a human subsidy due to either availability or preferences. C_LIO_LIOur preference and network models revealed that while hummingbird-plant network structure was similar across landscapes, the composition of important taxa shifted from native, wild species like Monarda and Impatiens to non-native, cultivated species like Salvia. C_LIO_LIUsing trait-based models of flower visitation, we found that hummingbirds preferred native, tubular, and red/orange flowers fitting the hummingbird pollination syndrome despite visiting >260 different plant species. Red and orange flowers were preferred across all seasons, suggesting color may be a reliable signal of nectar availability across species and contexts. Native and tubular flowers were strongly preferred during the breeding season, however, preferences relaxed during spring and fall migration. C_LIO_LIThese findings reveal the consistent preferences of Ruby-throated Hummingbirds for native, tubular, and red/orange flowers, and underscore how spatial and temporal factors reshape foraging behavior and trait preferences. Our results also highlight the value of community-collected data in characterizing plant-pollinator interactions across broad spatial and temporal scales. C_LI

ecology↗

bioRxiv2026

Inter-haplotype inversions and repeat expansion in the sexually deceptive orchid Chiloglottis trapeziformis

Chiloglottis trapeziformis is a sexually deceptive Australian orchid that provides a valuable system for studying orchid genome evolution, structural variation, and the molecular basis of specialized pollination. However, high-quality nuclear genome resources remain scarce for most orchids, particularly Australias diverse terrestrial lineages. To address this gap, we integrated PacBio HiFi, Oxford Nanopore ultra-long reads, and Hi-C chromatin-contact data to generate the first chromosome-scale, haplotype-resolved nuclear genome assembly for an Australian terrestrial orchid, Chiloglottis trapeziformis. Hi-C guided scaffolding resolved two haplotypes into 20 chromosomes each, consistent with the reported karyotype and genome size (2n=40, haplotype sizes of 1.58 Gb and 1.91 Gb). Genome completeness was high for both haplotypes, recovering 95.1% and 95.5% complete BUSCO genes for haplotype 1 and haplotype 2, respectively. De novo repeat annotation revealed a repeat-rich genome (85.79- 88.25% repetitive sequence), dominated by LTR retrotransposons. Evidence-guided annotation identified 16,287 and 16,548 protein-coding genes in Haplotype 1 and Haplotype 2, respectively. Phylogenetically informed comparisons placed C. trapeziformis as sister to Anoectochilus roxburghii among sampled Orchidoideae and showed broad gene-order conservation. Comparing the two haplotypes for structural variation, we identified large inter-haplotype inversions containing functionally annotated genes with detectable RNA expression, with focal examples further supported by local Hi-C contact patterns and breakpoint-level inspection. Inversion-overlapping genes did not show elevated dS relative to collinear background. This assembly and annotation resource provides a foundation for population and conservation genomics, structural and comparative analyses, and genome-enabled hypothesis testing of molecular traits underlying sexual deception in orchids. Significance statementSexually deceptive orchids use remarkable chemical, visual, and tactile mimicry to attract specific pollinators, but the genome resources needed to understand how these complex traits evolved remain scarce. By generating a chromosome-scale, haplotype-resolved genome for Chiloglottis trapeziformis, we provide the first genomic framework for the large and unique Australasian tribe Diurideae. We show extensive structural variation between haplotypes in an otherwise highly collinear genome, with several large inversions potentially impacting expressed genes. The absence of elevated coding divergence in these regions highlights structural variation as a potentially underappreciated driver of orchid genome evolution. This resource fills a major gap for Australian orchids and provides a foundation for linking genome structure with orchid diversification, conservation, and the evolution of sexual deception.

genomics↗

bioRxiv2026

Greater Amyloid Burden in Cognitive Networks in Preclinical Alzheimer's Disease

BackgroundIn preclinical Alzheimers disease (pAD), regional patterns of amyloid-{beta} (A{beta}) deposition are well characterized but it is unclear how this process varies across functional networks. ObjectiveDetermine how A{beta} accumulation in functional networks ("network-amyloid burden" [NAB]) varies by age, network type (cognitive vs. non-cognitive), and A{beta} status (A{beta}+/A{beta}-), and relates to cognition. Methods157 cognitively unimpaired adults (45-84 years; n=28 A{beta}+ per neuroradiological read) underwent brain MRI, amyloid PET (18F-florbetapir), and neuropsychological testing. NAB was calculated as the mean standard uptake value ratio within 7 networks categorized as cognitive (fronto-parietal, default mode, ventral and dorsal attention, limbic) or non-cognitive (somato-motor, visual). Linear mixed models tested how NAB varies across age, networks (by type and each separately), A{beta} status, and their interactions, and relationships between NAB and cognition. ResultsNAB increased with age, most prominently in fronto-parietal and default mode networks. NAB was higher in cognitive than non-cognitive networks, and this difference was more pronounced in A{beta}+ individuals. NAB was not significantly associated with cognition. ConclusionsCognitive brain networks are more vulnerable to amyloid accumulation with aging and in pAD than non-cognitive networks. Cognitive NAB may be useful for early detection and as a target for intervention in pAD.

neuroscience↗

bioRxiv2026

Mitochondrial Optic Atrophy (OPA)1 expression regulates the injury response to neonatal hypoxia-ischaemia.

Neonatal hypoxic-ischaemic encephalopathy is a leading cause of mortality and long-term neurodevelopmental impairment, in which mitochondrial dysfunction is central to injury progression, yet the molecular mechanisms linking mitochondrial dynamics to neuropathology remain incompletely defined. We combined analysis of human developmental transcriptomic datasets with in vitro primary astrocyte models and an established neonatal mouse model of hypoxia-ischaemia (postnatal day 9, Rice-Vannucci model) to investigate the role of the mitochondrial fusion protein Optic Atrophy 1 (OPA1). OPA1 expression and processing were assessed by quantitative PCR and western blotting, mitochondrial function by imaging and Seahorse bioenergetic assays, and mitochondrial DNA content by quantitative PCR in both astrocytes and whole-brain tissue following injury. Hypoxia-ischaemia induced rapid proteolytic processing of OPA1 in the neonatal brain and reduced OPA1 expression in astrocytes following oxygen-glucose deprivation. Genetic reduction of OPA1 in astrocytes resulted in mitochondrial fragmentation, impaired maximal respiration and spare respiratory capacity (p<0.05), and increased susceptibility to hypoxic stress (p<0.01). In vitro, OPA1 loss was associated with significant depletion of mitochondrial DNA (p<0.05), and mitochondrial DNA content was similarly reduced in the neonatal mouse brain 24 hours after hypoxia-ischaemia compared with controls (p<0.05). In contrast, OPA1 overexpression preserved mtDNA levels and significantly reduced in vivo brain tissue loss at 7 days after injury (p<0.05), while improving astrocyte survival following metabolic stress (p<0.001). These findings identify loss of mitochondrial DNA as a previously unrecognised component of mitochondrial pathology in neonatal hypoxic-ischaemic brain injury and demonstrate that OPA1 is a key determinant of mitochondrial integrity and bioenergetic resilience. Targeting OPA1-dependent pathways may represent a novel therapeutic strategy to limit brain injury following birth asphyxia.

neuroscience↗

bioRxiv2026

Unraveling a comparative landscape of protein-coding genes linked to neuroimmune function during adulthood consequent of prenatal alcohol exposure

BackgroundAn overwhelming body of evidence suggests neuroimmune dysfunction as a key underlying mechanism of FASD-associated adverse CNS outcomes. While few studies have highlighted the lingering effects of prenatal alcohol exposure (PAE) on producing specific immune factors, others suggest a primed neuroimmune state in adulthood, in which a proinflammatory bias is unmasked following subsequent immune activation in later-life. However, the PAE-induced neuroimmune landscape in adulthood remains poorly defined. We hypothesized that PAE induces long-term changes in gene expression linked to neuroimmune function that may be brain region-specific. MethodsUsing long-read next-generation RNA sequencing of brain tissues from a previously established model of a moderate PAE in mice, we compared across six regions: medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), hypothalamus, hippocampus, midbrain, and medulla. A comprehensive bioinformatics analysis investigated PAE-induced changes, dysregulated gene pathways, and transcriptional regulators with a focus on neuroimmune function. ResultsOur data identified at least 60 differentially expressed genes per brain region, many of which were associated with neuroimmune function. Upregulation of multiple proinflammatory factors and pathways was observed, suggesting ongoing baseline neuroimmune activation, potentially involving PXR, TNF, TLR4, the complement pathway, and various cytokine and chemokine signaling. A comparative analysis identified multiple upstream transcriptional regulators across multiple brain regions, including MECP2, TCF7L2, and IL-4. Importantly, this unbiased analysis revealed heterogeneity across brain regions in the activation of canonical immune pathways and highlighted previously unprecedented roles of pathways such as PXR, matrix metalloproteases, and cytokine signaling (e.g., IL-15, IL-27, IL-17) in PAE. ConclusionsPAE creates a unique inflammatory signature in the adult brain, even in the absence of secondary injury, with novel patterns of region-specific changes in genes implicated in glial-immune function. These data identified potential immune targets to elucidate the mechanisms underlying behavioral dysfunction and provide a framework for future therapeutic interventions.

neuroscience↗

bioRxiv2026

Hypertension is related to a slower radiotracer removal from lateral ventricles

BackgroundImpairment of brain waste removal contributes to Alzheimers disease etiology and progression. Although hypertension is a risk factor for dementia, little is known about how it affects measures of clearance in human brain. MethodsCross-sectional (n=159) and longitudinal (n=94) analysis of the relationship between blood pressure (BP) and brain clearance. The estimate of brain clearance was measured using positron emission tomography (PET) as the rate of radiotracer (MK-6240) efflux from the lateral ventricles in the 10-30-minute window after tracer injection. We also examined cerebral blood flow, PET-derived tau deposition in the medial temporal lobe, cognition and plasma biomarkers of neurodegeneration. At baseline we compared participants with (n=88) and without (n=71) hypertension. For longitudinal analyses we defined two groups based on systolic BP trajectories from baseline to follow-up: as long-term controlled (n=76) or uncontrolled BP (n=18). ResultsAt baseline, subjects with hypertension had lower ventricular clearance than normotensive controls (Cohens d=0.53, p=0.001). Over the course of the observation period (median 1.85 years) subjects in the uncontrolled BP group experienced a steeper reduction in clearance rates ({beta}=-5.88) than subjects in the controlled BP group ({beta}=-0.81, interaction p=0.039). ConclusionsOur study suggests that hypertension impairs brain clearance of fluids.

neuroscience↗

bioRxiv2026

Sexual recombination under tetrapolar mating can alter host-specialization boundaries between wheat- and barley-adapted stripe rust lineages

O_LIHost specialization is a major driver of genetic structure in fungal plant pathogens, but it remains unclear whether specialization on different cereal hosts prevents sexual recombination when mating-type compatibility is retained. We addressed this question in stripe rust, caused by Puccinia striiformis, by crossing wheat-adapted P. striiformis f. sp. tritici and barley-adapted P. striiformis f. sp. hordei, two divergent host-adapted forms that share common barberry (Berberis vulgaris) as a sexual host. C_LIO_LIControlled reciprocal crosses on barberry produced 18 aeciospore-derived progeny, demonstrating that wheat- and barley-adapted Puccinia striiformis can undergo sexual recombination despite strong host specialization during asexual infection. Chromosome-scale parental assemblies placed the homeodomain (HD) mating-type locus, containing bW-HD1 and bE-HD2, on chromosome 2 and the pheromone receptor (PR) mating-type locus, containing STE3 and mfa genes, on chromosome 6. HD restriction genotyping showed biparental inheritance in all progeny, with each progeny carrying one HD haplotype from each parent. Together with conservation of PR-associated coding sequences and amplification of STE3-associated markers in progeny, these results are consistent with retention of tetrapolar mating across the two host-adapted lineages. C_LIO_LIHost interaction phenotypes were assessed across wheat and barley differentials, near-isogenic lines and wild relatives. The parental isolates retained contrasting wheat- and barley-restricted profiles, whereas progeny did not reproduce either parental virulence profile, but instead showed recombinant infection patterns, including compatibility with both wheat and barley genotypes. C_LIO_LIThese findings indicate that host specialization in Puccinia striiformis does not necessarily prevent sexual compatibility on a shared alternate host. Together with retention of tetrapolar mating, alternate-host sexual reproduction may provide a route for genetic exchange between host-specialized pathogen populations, enabling recombination to generate new combinations of host-interaction traits when divergent pathogen lineages mate on a shared alternate host. C_LI

microbiology↗

bioRxiv2026

Network pharmacology-based discovery and experimental validation of novel drug repurposing candidates in Alzheimer's Disease

Despite a growing body of evidence implicating genetic variants and proteins encoded by them with risk and pathogenesis of Alzheimers disease (AD), this knowledge has not been successfully translated into effective AD treatments. We integrated current genomic, transcriptomic and proteomic profiles of AD into a network pharmacology framework that leverages comprehensive gene-gene and drug-target interactions. This approach allowed us to screen 2,413 drugs for repurposing opportunities in AD. Computational validation and drug prioritization was followed by experimental validation in 33 cell culture-based phenotypic assays combined with Bayesian hypothesis testing. Our network-based screen rediscovered drugs in clinical trials for AD, providing computational validation. Besides many cancer drugs, the screen identified three drugs previously implicated in AD-related endophenotypes: the primary bile acid chenodiol, arundine (3,3-diindolylmethane), and cysteamine. In analysis of results from culture-based phenotypic assays, large Bayes factors supported the hypothesized benefits of arundine and the chenodiol derivative, tauroursodeoxycholic acid (TUDCA), in amyloid-{beta} clearance and release and neuroinflammation. Follow-up network analyses mechanistically implicated Regulator of G protein signaling 4 (RGS4) in the plausible therapeutic actions of arundine and TUDCA. A network pharmacology approach identified TUDCA and arundine as promising repurposing candidates in AD that rescue disease-relevant molecular phenotypes by acting on AD-associated genes through regulation of G protein signaling.

systems biology↗

bioRxiv2026

mRNAfold: Co-optimization of Global Stability, Local Structure, and Codon Choice via Suboptimal Folding

mRNA medicines hold great promise, but designing sequences with high translation efficiency, robust in-solution stability, and manufacturability remains a major challenge due to the vast combinatorial space of synonymous coding sequences. Computational approaches such as mRNA folding algorithms have emerged as powerful tools by co-optimizing for in-solution stability and translation efficiency, yet current methods face important limitations. Here, we present "mRNAfold", an improved mRNA folding algorithm and software package that addresses these gaps by enabling efficient exploration of diverse near-optimal solutions, incorporating untranslated regions (UTRs), parallel execution, and supporting tunable control over local structural features across the mRNA. Thermodynamically optimized mRNAs from mRNAfold were more stable ({approx} 2-fold) in-solution than those generated by simple GC maximization for the same encoded protein. In addition, mRNAs designed to vary local structure near the start codon while maintaining consistent structure and codon optimality elsewhere showed a complex relationship between local structure near the start codon and protein production in cells. We observed no impact of structure in the start codon region for a set of mRNAs with high codon optimality, but it did impact protein production for a set of mRNAs with lower codon optimality. Together, these results underscore the potential of structure-aware, multi-objective design to improve mRNA medicines and offer a framework for exploring how sequence, structure, and expression are interrelated.

bioinformatics↗

bioRxiv2025

Complex Genomic Structural Variation Underlies Climate Adaptation among Eucalyptus species

Climate change threatens global natural forest ecosystems, however, our limited understanding of adaptive genomic variation in wild forest trees restricts our ability to address this threat. Eucalyptus species likely harbour many climate adaptive alleles considering their long-standing evolutionary success across the Australian continent, yet their complex genomic variation and adaptive implications remain undercharacterised. Here, we present a comprehensive pangenome analysis of Eucalyptus viminalis using haplotype-resolved genomes and population-level long-read sequencing spanning the species natural distribution. We discovered complex and simple structural variants (SVs) that doubled the haploid genome length (530 Mbp haploid to 1.1 Gbp pan-genome). Landscape genomic analyses with SVs identified CHILL1, a 400-kb cold-adaptation locus underlined by complex structural variation. Validation across 434 accessions from three Eucalyptus species confirmed the large-effects of CHILL1, which outperforms species classification at predicting cold adaptation. These findings demonstrate that wild tree populations harbour critical adaptive alleles that can expedite climate-informed restoration.

genomics↗

bioRxiv2025

Genome assembly of Spinifex sericeus provides insights into repetitive content and haplotype variation in a dioecious coastal grass

Spinifex sericeus (beach spinifex) is a perennial, dioecious grass native to coastal ecosystem of Oceania that has an important role in dune stability. We present a near telomere-to-telomere, haplotype-resolved nuclear genome alongside complete organelle genomes of S. sericeus. The nuclear genome is highly repeat-rich, dominated by long terminal repeat (LTR) retrotransposons. Comparative analysis of the two haplotypes reveals extensive structural variation and high levels of duplication that are suggestive of active and expanding LTRs that may drive genome evolution and expansion in this species. The chloroplast genome exhibits heteroplasmy, having two distinct circular configurations spanning 138 kbp each. The complex mitochondrial genome consists of a large linear component spanning 1.85 Mbp and a small circular 134 kbp component. These genomic resources provide a foundation for advancing research on sex determination and stress adaptation in grasses, and well as practical applications in crop improvement and genetically informed coastal dune restoration. Significance statementThe reference genome of Spinifex sericeus provides a foundational resource for understanding adaptations to the harsh coastal dune environment, including saline conditions, extreme temperatures, and drought. The genome enables comparative studies within Poaceae, where current reference genomes are dominated by crop species, and supports conservation and restoration efforts for coastal ecosystem management.

genomics↗

bioRxiv2025

The promise of AlphaFold for gene structure annotation

BackgroundAs sequencing technology improves, more genomes become available. Most lack annotation, automated methods are error prone, and few genomes are ever manually curated due to time and cost. Protein structure prediction software may provide new angles for assessing and improving gene models without requiring experimental data. In this paper, we explore whether scores from protein structure prediction can aid in scoring gene model quality. We chose three species (Fusarium graminearum, Toxoplasma gondii, and Aspergillus fumigatus) from the VEuPathDB database which have collectively undergone more than 1000 manual curation events. We modelled translations of the gene models with AlphaFold 3, before and after curation, collecting various scores. Then we carried out structure searching of the PDB with Foldseek and sequence-based domain identification using InterProScan. We profiled the scores produced by these methods to identify those best for gene model assessment. ResultsAlphaFold 3 scores strongly favoured manually improved over pre-improvement models, supporting 75% of manually-curated changes in F. graminearum, 65% in T. gondii, and 84% in A. fumigatus (the lower percentage in T. gondii attributed to a high level of disorder). Further, combining scores across multiple tools (AlphaFold 3, Foldseek and InterProScan) provided additional improvements in model scoring. ConclusionOverall, the most discriminative scores combined outputs of AlphaFold 3 and Foldseek. Our results therefore highlight the potential of scores derived from deep learning-based protein structure prediction for scoring gene models in the absence of experimental data. Future work should focus on intrinsically disordered regions and developing integrated tools to apply this approach.

bioinformatics↗

bioRxiv2025

Hepatic cellular stress response pathways exhibit species differences in basal and inducible activity

Cellular stress response pathways such as the NRF2 oxidative stress response, endoplasmic reticulum (ER) stress response and macroautophagy afford protection against many forms of drug toxicity, including the liver toxicity associated with the formation of reactive drug metabolites. To maximise the translatability of preclinical toxicology studies, an understanding of the relative hepatic stress response capacities of humans and widely-used preclinical animal species is vital. In control liver tissue, the basal gene and protein expression of stress response pathway components was found to be greater in rodents than non-rodent preclinical species and humans. In addition, following in vitro exposure to pharmacological modulators of the NRF2 and ER stress responses, rodent hepatocytes generally displayed a greater capacity, relative to those of non-rodent preclinical species and humans, for adaptation to cellular stress. Consistent with the reported lower concordance of drug toxicity between humans and rats, the latter displayed a greater level of Torin1-induced autophagic flux than all other species, while the robust transcriptional responses to thapsigargin-induced endoplasmic reticulum stress and Bardoxolone- or Ki696-mediated NRF2 activation were comparable between mouse and rat hepatocytes. In all, our results indicate that rodent preclinical species possess a greater basal and adaptive hepatic capacity for mitigation of chemical insult than non- rodent preclinical species and humans. This study represents the first to provide a comprehensive comparison of stress response pathway capacity of humans and the animal species most commonly used for preclinical drug safety assessment. Our findings can be used to inform the selection of species for safety testing of drugs with a liability for reactive metabolite-mediated liver toxicity.

pharmacology and toxicology↗

bioRxiv2025

Evolutionary Rewiring of Anthocyanin Biosynthesis Pathway in Poaceae

Poaceae is a species-rich family of plants in the monocots harboring many important crop species. As grasses, these plants lack striking flowers that are typically pigmented by anthocyanins. Here, we investigated the anthocyanin biosynthesis genes in Poaceae and characterized several striking patterns. (1) An independently evolved MYB lineage (ncaMYB) is responsible for the regulation of the anthocyanin biosynthesis in Poaceae. (2) The independently evolved BZ2 lineage replaced the otherwise widespread TT19/An9 lineage as anthocyanin-related glutathione S-transferase in Poaceae. (3) The anthocyanin biosynthesis genes ANS, arGST (BZ2), and the anthocyanin biosynthesis activating MYB (ncaMYB) appear to be absent from the genus Brachypodium. These observations could be explained by a loss of the anthocyanin biosynthesis at the basis of the Poaceae, followed by an evolutionarily independent regain and again a loss of the anthocyanin biosynthesis in Brachypodium.

plant biology↗