Biology subjects

Wright, J.

Publications and source records attributed to Wright, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Canopy traits reveal climate-associated genetic differentiation in a California oak common garden

Background and Aims. Phenotypic variation in plant populations reflecting historical climate adaptation may affect performance under future climates. In long-lived trees, height and stem diameter are commonly used to assess growth, but these measures may not fully capture complementary structural and functional dimensions of performance, such as canopy development and vigor. We investigated whether canopy traits reveal climate-associated genetic differentiation in Quercus lobata. Methods. Using drone-based remote sensing of 1,395 12-year-old Quercus lobata trees from 601 families in a common garden, we quantified canopy volume and greenness, using the Normalized Difference Vegetation Index (NDVI). Previous analyses indicated that trees originating from warmer climates grew more in common gardens than those from cooler climates. To assess whether canopy traits showed similar patterns, we tested for family-level variation in each trait and associations with climate of origin. Key Results. Canopy volume and greenness showed significant genetic variation among families and significant associations with climate of origin. Trees from hotter climates had greater canopy volume and greenness than trees from cooler climates. Conclusions. These covarying traits provide novel evidence of climate-associated genetic differentiation in tree performance, consistent with historical climate selection. Trees originating from climates with hot summers, moderate winters, and low precipitation performed best in the garden, suggesting that they will perform better than trees adapted to cool, wet conditions under future climate change.

evolutionary biology↗

bioRxiv2026

Hyperactivation of β-catenin rewires mitochondrial fuel selection in liver cancer cells

Metabolic state is tightly linked to cell fate, and expression of the mitochondrial pyruvate carrier (MPC), which imports pyruvate into mitochondria, is a robust marker of it. The transcriptional regulators that set metabolic state, however, remain poorly defined. In the liver, {beta}-catenin is one of the determinants of metabolic zonation, and activating CTNNB1 mutations are frequent in hepatocellular carcinoma. Here we show that {beta}-catenin regulates metabolic state in liver cancer cells. An unbiased CRISPR screen that uses endogenous MPC1 transcript abundance as the marker identifies CTNNB1. Activating {beta}-catenin pharmacologically or genetically reduces MPC1 and MPC2 transcript and protein levels, and MPC expression is also low in {beta}-catenin-driven liver tumors in vivo. Beyond the MPC, {beta}-catenin activation impairs assembly of respiratory Complexes III and IV, reduces mitochondrial DNA content and respiratory capacity, elongates mitochondrial networks and remodels the lipidome. Stable isotope tracing shows reduced entry of glucose- and lactate-derived carbon into the TCA cycle alongside increased oxidation of palmitate and oleate. These findings identify {beta}-catenin as a regulator of metabolic state that drives a fuel switch from carbohydrate to fatty acid oxidation in liver cancer cells.

biochemistry↗

bioRxiv2026

Multisite Evaluation of an Amplification-based Nanopore Sequencing Solution to Analyze Challenging Clinically Relevant Variants in Genes Associated with Hereditary Diseases

PurposeCarrier screening for hereditary conditions is challenged by genes with complex genomic architecture, where short-read sequencing can fail to detect clinically relevant variants. This study evaluated a unified, amplification-based nanopore sequencing workflow across multiple laboratories for comprehensive analysis of such loci. MethodsA modular long-read sequencing assay was evaluated across five laboratories using targeted PCR enrichment, Oxford Nanopore sequencing, and automated variant analysis. The workflow interrogated genes associated with spinal muscular atrophy, thalassemia, cystic fibrosis, fragile X syndrome, congenital adrenal hyperplasia, Gaucher disease, and hemophilia A. Performance was assessed against orthogonal methods for single nucleotide variants (SNVs), indels, copy-number variants, repeat expansions, and structural rearrangements. ResultsAcross 882 unique samples (1,266 tests), overall agreement with comparator methods exceeded 96% for variant-level detection and 97% for genotype status classification. Long-read sequencing enabled phasing of paralogous loci, integrated sizing and interruption analysis for FMR1 repeats, and simultaneous detection of SNVs and structural variants in globin loci and CYP21A2-TNXB region, reducing reliance on multiple workflows. ConclusionThis multisite evaluation suggests that targeted long-read sequencing can consolidate complex variant detection into a single workflow, improving analytical completeness and operational efficiency for carrier screening.

genetics↗

bioRxiv2026

STAT1 expression in myeloid cells restrains murine norovirus-induced hepatitis and fibrosis

Background & AimsRare cases of non-hepatotropic virus (NHV) infection in humans can cause severe hepatitis and even acute liver failure. Clinically relevant animal models of NHV-induced hepatitis are limited, contributing to the incomplete understanding of pathological mechanisms. Murine norovirus (MNV) elicits hepatosplenomegaly in mice lacking the antiviral immune effector Signal Transducer and Activator of Transcription-1 (STAT1), providing a model to investigate mechanisms of NHV-induced hepatic pathology. MethodsSTAT1-sufficient and -deficient (Stat1Het, Stat1KO) littermates infected intravenously (i.v.) with MNV strain CR6 were assessed for hepatic inflammation and viral burden. Cell types and molecular pathways associated with hepatic pathology in CR6-infected Stat1KO mice were identified by flow cytometry and RNAseq of liver tissue. The relative importance of hematopoietic vs non-hematopoietic expression of STAT1 in restricting CR6 replication and maintaining tissue homeostasis was assessed in bone marrow chimeras. ResultsMNV CR6 Stat1KO mice developed severe hepatitis with patchy hepatocellular necrosis and localized enrichment of CR6-infected myeloid cells, particularly macrophages. Gene set enrichment analysis (GSEA) of hepatic biopsies isolated from CR6-infected Stat1KO mice suggested dysregulated myeloid cell activation and indicated similarities between murine and human hepatic pathologies. STAT1 expression in hematopoietic cells was protective against hepatic viral dissemination, but hematopoietic STAT1-deficiency permitted persistent hepatic MNV infection, facilitating dysregulated myeloid cell activation and hepatic fibrosis. ConclusionsThese results demonstrate that the role of STAT1 extends beyond restricting MNV dissemination and suggest that STAT1-dependent regulation of myeloid cell activation prevents acute hepatic necroinflammation and secondary fibrosis. This model of MNV-induced hepatitis may prove valuable in elucidating mechanisms of rare clinical complications. SynopsisMechanisms driving acute hepatitis caused by non-hepatotropic viruses are not well understood. We describe a model of non-hepatotropic murine norovirus infection that reliably induces liver pathology and identify a requirement for STAT1 expression in myeloid cells to promote antiviral immunity and hepatic tissue protection. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/720966v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@4ef59forg.highwire.dtl.DTLVardef@1dfac58org.highwire.dtl.DTLVardef@1abe41dorg.highwire.dtl.DTLVardef@d59e9_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2026

MINGL Quantifies Borders, Gradients, and Heterogeneity in Multicellular Tissue Organization

Tissues are organized with interacting multicellular organizational units whose interfaces and transitions shape function in health and disease. Current spatial-omics analyses typically assign cells to a single cellular neighborhood--ignoring natural gradients, heterogeneity, and borders. Here we present MINGL (Mixture-based Identification of Neighborhood Gradients with Likelihood estimates), a probabilistic framework that converts existing neighborhood annotations into continuous measures of tissue architecture. MINGL models each cell by multi-membership probabilities across hierarchical organizational units and uses these probabilities to identify enriched cells at interfaces between units, constructs interaction networks across hierarchical scales, quantifies compositional gradient transitions, measures context-specific composition heterogeneity, and provides a starting point for neighborhood resolution. Across multiple spatial-omic datasets spanning melanoma, healthy intestine, and Barretts Esophagus progression, MINGL detected innate immune-enriched interfaces at tumor and anatomical interfaces, plasma cell niches linking cellular neighborhoods, distinct regimes of sharp and gradual transitions between organizational states, and disease-associated neighborhood remodeling. By treating neighborhood assignment uncertainty as a biological signal rather than noise, MINGL unifies discrete and continuous representations of tissue organization and makes tissue architecture measurable, comparable, and scalable across biological scales and spatial-omics platforms.

systems biology↗

bioRxiv2026

Chromatin assembly at replication forks enables differentiation of human iPSCs

DNA replication is both productive and disruptive, synthesising new DNA while dismantling chromatin to allow fork progression. Because of its disruptive nature, DNA replication has been suggested to enable chromatin changes facilitating cell fate transitions. However, the role of DNA replication in cell fate transitions remains incompletely understood. Here we show that upon differentiation of human induced Pluripotent Stem Cells (iPSCs) into presomitic mesoderm, DNA replication allows hundreds of proteins, including transcription factors, histone chaperones, and histone methyltransferases, to access chromatin. Moreover, H3K9 methylation is enhanced upon differentiation through a DNA replication-coupled process. Most of the proteins recruited to (or evicted from) nascent chromatin during differentiation are already present in iPSCs, suggesting they may play a role in the early response to differentiation. Among these, we identified ERH and SETDB1 as essential for mesoderm differentiation. Our work reveals a new paradigm to explore: how differentiation signals exploit the replisome interactome to enable rapid chromatin changes.

cell biology↗

bioRxiv2025

microRNA-21 promotes dysregulated lipid metabolism and hepatocellular carcinoma

Backgrounds and AimsThe prevalence of hepatocellular carcinoma (HCC) is rising in parallel with increasing obesity and metabolic dysfunction-associated steatohepatitis (MASH). MicroRNAs are key post-transcriptional regulators of gene expression and are attractive targets for HCC therapy. Here we sought to identify and characterize dysregulated microRNAs in MASH-driven HCC (MASH-HCC). Approach and ResultsWe profiled microRNA expression in liver tissue from patients with MASH and/or MASH-HCC and in zebrafish HCC driven by activated {beta}-catenin (ABC), one of the most commonly mutated oncogenes in MASH-HCC. We found significant overlap between dysregulated human and zebrafish miRNAs, including miR-21, which was increasingly upregulated from normal liver to MASH to MASH-HCC. We generated transgenic zebrafish that overexpress or sponge (downregulate) miR-21. We found that miR-21 overexpression caused larval liver overgrowth and increased HCC while miR-21 sponge suppressed {beta}-catenin-driven larval liver overgrowth. By performing histologic and lipidomic analysis, we found that overexpression of miR-21, like ABC, suppressed lipid accumulation in response to a high cholesterol diet and increased accumulation of acylcarnitines. ConclusionsHere we characterize microRNA dysregulation in MASH and MASH-HCC in patients, identify miR-21 as increasingly dysregulated from MASH to MASH-HCC, and delineate the impacts of miR-21 overexpression on lipid metabolism and hepatocarcinogenesis in zebrafish {beta}-catenin-driven HCC. This study shows that miR-21, which is similarly dysregulated in human and zebrafish HCC, promotes lipid metabolic changes that may help drive hepatocarcinogenesis.

cancer biology↗

bioRxiv2025

A non-coding role for trypanosome VSG transcripts in allelic exclusion

Bloodstream-form African trypanosomes display mono-telomeric expression of a Variant Surface Glycoprotein (VSG) gene in an inter-chromosomally bridged transcription and splicing compartment, such that the dominant gene produces 10,000 times more transcript than excluded VSG genes. Antigenic variation, whereby parasites switch to express other VSGs, then underpins a robust host immune evasion strategy. Specific chromatin and RNA-associated factors are required to maintain VSG exclusion, but our understanding of the mechanisms involved remains incomplete. Here we show that the VSG transcript impacts allelic competition. We induced either specific translation blockade by recruiting MS2 coat protein to the active VSG 5-untranslated region, or VSG transcript depletion using RNA interference. Neither perturbation substantially compromised exclusion of native VSGs, as determined by transcriptomic analyses. In contrast, exclusion of a VSG transgene was compromised when the native transcript was transiently depleted. Notably, while both perturbations blocked cytokinesis, an additional round of DNA replication and mitosis was observed when the transcript, known to be stabilized by a bloodstream-form specific cyclin-like F-box protein, was translationally blocked. We conclude that the VSG transcript is a bi-functional coding and non-coding RNA that participates in allelic competition to establish exclusion. Significance statementAllelic exclusion mechanisms underpin immune evasion in parasites and olfaction in mammals but the mechanisms responsible remain mysterious. VSG exclusion factors have been identified in trypanosomes, while RNA has been implicated in olfactory receptor exclusion, and in var gene exclusion in the parasites that cause malaria. The current study demonstrates a role for RNA in VSG exclusion in trypanosomes.

molecular biology↗

bioRxiv2025

Hyperlipidemia drives tumor growth in a mouse model of obesity-accelerated breast cancer growth.

Obesity is an established risk factor for breast cancer (BC), yet the specific mechanisms driving this association remain unclear. Dysregulated lipid metabolism has emerged as a key factor in cancer cell biology. While obesity is often accompanied by hyperlipidemia, the isolated impact of elevated lipid levels on BC growth has not been experimentally tested. Using the E0771 orthotopic model of obesity-accelerated BC growth in immune-competent mice, we investigated the direct role of systemic lipids in tumor growth. Combining dietary and genetic mouse models, we show that elevated circulating lipids are sufficient to accelerate BC tumor growth even in the absence of obesity or alterations in blood glucose and/or insulin levels. Pharmacological lowering of systemic lipid levels attenuates BC growth in obese mice, suggesting a direct role for lipids in fueling tumor expansion. Notably, we also show that weight loss alone, without a corresponding reduction in lipid levels such as that induced by a ketogenic diet, fails to protect against BC, highlighting the necessity of targeting lipid metabolism in obesity-associated BC. Our findings establish hyperlipidemia as a critical driver of BC progression and suggest that lipid-lowering interventions may be a promising strategy to mitigate BC risk in obese individuals.

cancer biology↗

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

Towards explaining the fertility gap in farmed Pekin ducks

Maximising reproductive success is crucial to animal production systems, particularly in meeting global demands for animal products and improving commercially important traits. However, while social interactions and mating strategies are known to influence reproductive success in wild populations, their consideration in agricultural systems remains limited. Using an interdisciplinary framework that combines concepts from behavioural ecology and quantitative genetics in an animal breeding context, we investigated the role of sperm limitation and polygynous mating strategies (female polyandry, male monopolisation of females and male polygamy) in limiting female reproductive success in farmed Pekin ducks (Anas platyrthynchos domestica). We assessed the impact of these behaviours on chick production and quantified their genetic and environmental (co)variance. Our results revealed that the number of dam mates positively influenced chick production in female ducks. However, contrary to our expectation, skew in chick paternity (our measure of male monopolisation) was associated with increased female chick production, challenging the hypothesis that male monopolisation limits the sperm available to females and reduces their reproductive success. We found no evidence that male polygamy led to decreased female chick production. Genetic analysis revealed that female mate number and reproductive skew exhibit genetic variance, providing opportunities for targeted selection to enhance chick production. However, there was a negative genetic association between female polyandry and skew in chick paternity, suggesting a trade-off between these traits that would need to be considered in future selection programmes. Our findings highlight how concepts from behavioural ecology can be incorporated into breeding programmes, providing new opportunities to develop effective and sustainable breeding strategies.

evolutionary biology↗

bioRxiv2024

Genomic signature of reproductive isolation between the last two remnant populations of Torrey pine (Pinus torreyana Parry)

Tree species are often locally adapted to their environments, but the extent to which environmental adaptation contributes to incipient speciation is unclear. One of the rarest pines in the world, Torrey Pine (Pinus torreyana Parry), persists naturally across one island and one mainland population in southern California. The two populations are morphologically and genetically differentiated, but experience some connectivity, making it an ideal system for assessing the evolution of reproductive isolation. Previous work has found evidence of heterosis in F1 mainland-island hybrids, suggesting genetic rescue could be beneficial in the absence of reproductive barriers. Using ddRADseq and GWAS for a common garden experiment of island, mainland, and F1 individuals, we identified candidate loci for environmentally-driven reproductive isolation, their function, and their relationship to fitness proxies. By simulating neutral evolution and admixture between the two populations, we identified loci that exhibited reduced heterozygosity in the F1s, evidence of selection against admixture. SNPs with reduced F1 heterozygosity were enriched for growth and pollination functions, suggesting genetic variants that could be involved in the evolution of reproductive barriers between populations. One locus with reduced F1 heterozygosity exhibited strong associations with growth and reproductive fitness proxies in the common garden, with the mainland allele conferring increased fitness. If this locus experiences divergent selection in the two natural populations, it could promote their reproductive isolation. Finally, although hybridization largely reduced allele fixation in the F1s initially, indicating heterosis is likely due to the masking of deleterious alleles, the emergence of reproductive isolation between populations may diminish the longer-term benefits of genetic rescue in F2 or advanced-generation hybrids. As Torrey pine is a candidate for interpopulation genetic rescue, caution is warranted where longer-term gene flow between diverged populations may result in reduced fitness if barriers have evolved.

genomics↗

bioRxiv2024

Human cytomegalovirus extensively re-organizes the human genome, diminishing TEAD1 transcription factor activity

Human cytomegalovirus (HCMV) infects up to 80% of the worlds population. Here, we show that HCMV infection leads to widespread changes in human chromatin accessibility and chromatin looping, with hundreds of thousands of genomic regions affected 48 hours after infection. Integrative analyses reveal HCMV-induced perturbation of Hippo signaling through drastic reduction of TEAD1 transcription factor activity. We confirm extensive concordant loss of TEAD1 binding, active H3K27ac histone marks, and chromatin looping interactions upon infection. Our data position TEAD1 at the top of a hierarchy involving multiple altered important developmental pathways. HCMV infection reduces TEAD1 activity through four distinct mechanisms: closing of TEAD1-bound chromatin, reduction of YAP1 and phosphorylated YAP1 levels, reduction of TEAD1 transcript and protein levels, and alteration of TEAD1 exon-6 usage. Altered TEAD1-based mechanisms are highly enriched at genetic risk loci associated with eye and ear development, providing mechanistic insight into HCMVs established roles in these processes.

genomics↗

bioRxiv2024

Oomycete communities in lowland tropical forest soils vary in abundance and are composed of saprophytes and pathogens of seeds and seedlings of multiple plant species.

PremiseThe soils in lowland tropics are teeming with microbial life which can impact plant community structure and diversity through plant-soil feedbacks. While bacteria and fungi have been the focus of most studies in the tropics, the oomycetes may have an outsized effect on seed and seedling health and survival, given their affinity for environments with increased precipitation and temperature. MethodsWe assessed the diversity and pathogenicity of oomycete species present in a lowland tropical forest in Panama. We used both a culture dependent leaf-baiting assay and culture independent soil DNA metabarcoding methods to quantify zoospore abundance and species diversity. A subset of the isolates from the baiting assay were used to evaluate pathogenicity and aggressiveness on seedlings of three tree species. Key resultsOomycetes are ubiquitous and common members of the soil microbial community in lowland tropical forests and zoospore abundance was far greater compared to similar studies from temperate and mediterranean forests. We also observed variation in oomycete species ability to infect host plants. Species of Pythium were more aggressive, while species of Phytopythium caused less disease but were more diverse and commonly isolated from the soil. Finally, we found that individual hosts accumulate a distinct oomycete community and was the only factor that had an effect community structure. ConclusionsCollectively, these finding demonstrate that oomycetes are ubiquitous, host-generalist pathogens and saprophytes, that have the potential to impact seed and seedling survival in lowland tropical forests

ecology↗

bioRxiv2024

Disentangling the age-dependent causal pathways affecting multiple paternity in house sparrows

The causes of variation in multiple paternity (MP) in socially monogamous birds have received considerable attention. Traits like age and age-dependent morphology have been shown to be important for the distribution of MP. However, most studies fail to separate between the different processes underlying age-effects on MP, such as selective disappearance (that is, higher survival probability for certain phenotypes) versus individually plastic changes in morphology and mating behaviour with age. Using Bayesian multi-level path analysis on a long-term dataset from a house sparrow (Passer domesticus) metapopulation, we disentangle the effects of age on male and female MP, both independently from and through morphological traits. Age was a key determinant of MP for males when accounting for morphological traits, with males having MP more often as they get older (plastic component of age) and not due to disappearance of males unsuccessful to get MP (selective disappearance), challenging good genes explanations for MP. Conversely, selective disappearance explained the higher levels of MP in older females, suggesting that higher quality females have MP more often than lower quality females. We show how an appropriate statistical decomposition of age-components and age-dependent processes provides insights to the biological drivers of MP.

ecology↗

bioRxiv2024

De novo annotation of the wheat pangenome reveals complexity and diversity of the hexaploid wheat pan-transcriptome

Wheat is the most widely cultivated crop in the world with over 215 million hectares grown annually. However, to meet the demands of a growing global population, breeders face the challenge of increasing wheat production by approximately 60% within the next 40 years. The 10+ Wheat Genomes Project recently sequenced and assembled to chromosome level the genomes of nine wheat cultivars to develop our understanding of genetic diversity and selection within the pan-genome of wheat. Here, we provide a wheat pan-transcriptome with de novo annotation and differential expression analysis for these wheat cultivars, across multiple different tissues and whole seedlings sampled at dusk/dawn. Analysis of these de novo annotations facilitated the discovery of genes absent from the Chinese Spring reference, identified genes specific to particular cultivars and defined the core and dispensable genomes. Expression analysis across cultivars and tissues revealed conservation in expression between a large core set of homeologous genes, but also widespread changes in subgenome homeolog expression bias between cultivars. Co-expression network analysis revealed the impact of divergence of sub-genome homeolog expression and identified cultivar-specific expression profiles. In a case study utilising both the newly constructed wheat pan-genome and pan-transcriptome we demonstrate prevalent variation in the prolamin superfamily and immune-reactive proteins across the pan-cultivars.In summary, this work provides both a valuable resource for the wider wheat community and reveals diversity in gene content and expression patterns between global wheat cultivars.

genomics↗

bioRxiv2023

PARP inhibitors enhance reovirus-mediated cell killing through the death-inducing signaling complex (DISC) with an associated NF-kappa B-regulated immune response.

Oncolytic Reovirus type 3 Dearing (RT3D), is a naturally occurring double-stranded (ds) RNA virus that is under development as an oncolytic immunotherapy We used an unbiased high-throughput cytotoxicity screen of different targeted therapeutic agents with the aim of identifying potential drug-viral sensitizers to enhance RT3D tumour killing. Talazoparib, a clinical poly(ADP)-ribose polymerase 1 (PARP-1) inhibitor, was identified as a top hit and found to cause profound sensitisation to RT3D. This effect was not seen with other classes of oncolytic virus and was not mediated by enhanced viral replication or PARP inhibitor-related effects on the DNA damage response. RT3D interacts with retinoic acid-induced gene-1 (RIG-I) and activates PARP-1, with consequent PARylation of components of the extrinsic apoptosis pathway. Pharmacological and genetic inhibition of PARP-1 abrogates this PARylation and increases levels of extrinsic apoptosis, NF-kB signalling and pro-inflammatory cell death. Direct interaction between PARP-1 and RIG-I following RT3D/talazoparib treatment is a key factor in activating downstream signaling pathways that lead to IFN-{beta} and TNF-/TRAIL production which, in turn, amplify the therapeutic effect through positive feedback. Critically, it was possible to phenocopy the effect of RT3D through the use of non-viral ds-RNA therapy and RIG-I agonism. In in vivo studies, we demonstrated profound combinatorial efficacy of RT3D and talazoparib in human A375 melanoma in immunodeficient mice. More impressively, in immunocompetent mouse models of 4434 murine melanoma, we achieved 100% tumour control and protection from subsequent tumour rechallenge with the combination regimen. Correlative immunophenotyping confirmed significant innate and adaptive immune activation with the combination of RT3D and PARP inhibition. Taken together, these data provide a clear line of sight to clinical translation of combined regimens of PARP inhibition or ds-RNA agonism, with either viral or non-viral agents, in tumour types beyond the relatively narrow confines of current licensed indications for PARP inhibition.

cancer biology↗

bioRxiv2023

A genome sequence for the threatened whitebark pine

Whitebark pine (WBP, Pinus albicaulis) is a white pine of subalpine regions in western contiguous US and Canada. WBP has become critically threatened throughout a significant part of its natural range due to mortality from the introduced fungal pathogen white pine blister rust (WPBR, Cronartium ribicola) and additional threats from mountain pine beetle (Dendroctonus ponderosae), wildfire, and maladaptation due to changing climate. Vast acreages of WBP have suffered nearly complete mortality. Genomic technologies can contribute to a faster, more cost-effective approach to the traditional practices of identifying disease-resistant, climate-adapted seed sources for restoration. With deep-coverage Illumina short-reads of haploid megametophyte tissue and Oxford Nanopore long-reads of diploid needle tissue, followed by a hybrid, multistep assembly approach, we produced a final assembly containing 27.6 Gbp of sequence in 92,740 contigs (N50 537,007 bp) and 34,716 scaffolds (N50 2.0 Gbp). Approximately 87.2% (24.0 Gbp) of total sequence was placed on the twelve WBP chromosomes. Annotation yielded 25,362 protein-coding genes, and over 77% of the genome was characterized as repeats. WBP has demonstrated the greatest variation in resistance to WPBR among the North American white pines. Candidate genes for quantitative resistance include disease resistance genes known as nucleotide-binding leucine-rich-repeat receptors (NLRs). A combination of protein domain alignments and direct genome scanning was employed to fully describe the three subclasses of NLRs (TNL, CNL, RNL). Our high-quality reference sequence and annotation provide a marked improvement in NLR identification compared to previous assessments that leveraged de novo assembled transcriptomes.

genomics↗