Biology subjects

Powell, D.

Publications and source records attributed to Powell, D..

At least 19 recordsLinked to original sources

bioRxiv2025

Brain serotonin circuit reverses decline in physical activity with age

Physical inactivity increases with age and is the fourth leading risk factor for mortality. Establishing the mechanisms underpinning declining physical activity (PA) with age has remained both elusive and difficult to overcome. Older (50-70 years old) compared with younger (17-30 years old) UK participants showed reduced PA, and this profile was effectively modelled in mice. Analysis of brain serotonin (5-HT) neurons in the dorsal raphe (DR) revealed altered firing activity in older mice. Chemogenetically mimicking this 5-HTDR tone in young adult mice produced an older adult PA profile. Genetically blocking 5-HT activity at 5-HT2C receptors (5-HT2CRs) prevented the decline in PA with age. Importantly, barring 5-HT action at 5-HT2CRs specifically within the ventral tegmental area restored youthful PA levels and strength in older mice. These data fill a longstanding knowledge gap by defining brain circuitry programming the decline in PA with age, and importantly, a means to reverse it.

neuroscience↗

bioRxiv2024

Myeloid cell networks determine reinstatement of original immune environments in recurrent ovarian cancer

Immunotherapy has produced disappointing results in recurrent ovarian cancer (OC). However, the prognostic value of tumour-infiltrating lymphocytes (TILs) is largely based on the analysis of treatment-naive tumours. To understand the immunobiology of recurrent cancers, and their evolution, we profiled 170 patient-matched primary-recurrent OC samples from 69 patients of two independent cohorts. By capturing heterogeneous TIL distributions, we identified four immune phenotypes associated with differential prognosis, TILs states and TILs:myeloid networks, which dictate malignant evolution after chemotherapy and recurrence. Notably, recurrent tumours recapitulate the immunogenic patterns of original cancers. Mirroring inflamed human OC, preclinical recurrent Brca1mut tumours maintained activated TILs:dendritic cells (DCs) niches and immunostimulatory tumour-associated macrophages (TAMs). Conversely, recurrent Brca1wt tumours displayed loss of TILs:DCs niches and accumulated immunosuppressive myeloid networks featuring Trem2/ApoEhigh TAMs and Nduf4l2high/Galectin3high malignant states. Our study highlights that persistent immunogenicity in recurrent OC is governed by the crosstalk between dissimilar myeloid cells and TILs, which is BRCA-dependent.

immunology↗

bioRxiv2024

A basic framework governing splice-site choice in eukaryotes

Changes in splicing are observed between cells, tissues, organs, individuals, and species. These changes can mediate phenotypic variation ranging from flowering time differences in plants to genetic diseases in humans. However, the genomic determinants of splicing variation are largely unknown. Here, we quantified the usage of individual splice-sites and uncover extensive variation between individuals (genotypes) in Arabidopsis, Drosophila and Humans. We used this robust quantitative measure as a phenotype and mapped variation in splice-site usage using Genome-Wide Association Studies (GWAS). By carrying out more than 130,000 GWAS with splice-site usage phenotypes, we reveal genetic variants associated with differential usage of specific splice-sites. Our analysis conclusively shows that most of the common, genetically controlled variation in splicing is cis and there are no major trans hotspots in any of the three analyzed species. High-resolution mapping allowed us to determine genome-wide patterns that govern splice-site choice. We reveal that the variability in the intronic hexamer sequence (GT[N]4 or [N]4AG) differentiates intrinsic splice-site strength and is among the primary determinants of splice-site choice. Experimental analysis validates the primary role for intronic hexamer sequences in conferring splice-site decisions. Transcriptome analyses in diverse species across the tree of life reveals that hexamer rankings explains splice-site choices from yeast to plants to humans, forming the basic framework of the splicing code in eukaryotes.

genetics↗

bioRxiv2023

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study

ObjectiveThe intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group. MethodsA state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. ResultsAcross all epilepsies, reduced total cerebellar volume was observed (d=0.42). Maximum volume loss was observed in the corpus medullare (dmax=0.49) and posterior lobe grey matter regions, including bilateral lobules VIIB (dmax= 0.47), Crus I/II (dmax= 0.39), VIIIA (dmax=0.45) and VIIIB (dmax=0.40). Earlier age at seizure onset ({eta}{rho}2max=0.05) and longer epilepsy duration ({eta}{rho}2max=0.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. SignificanceWe provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy. Key pointsO_LICerebellar involvement in epilepsy is poorly understood within current cortico-centric models of this disease C_LIO_LIWe used a novel, deep learning segmentation tool to parcellate the cerebellum into 28 anatomical subunits using an international MRI dataset of 1,602 individuals with epilepsy (aged between 18 and 65 years old) including temporal lobe epilepsy with hippocampal sclerosis (TLE-HS, n=562), TLE non-lesional (TLE-NL, n=284), generalised genetic epilepsy (GGE, n=186) and extra temporal focal epilepsy (ETLE, n=251) and 1,022 controls. C_LIO_LIAcross all epilepsies (vs. controls) robust changes in the corpus medullare and posterior lobe "non-motor" regions were observed, with maximal differences in bilateral VIIB and Crus II lobules. Lower volume of these regions correlated with longer disease duration. Anterior "motor lobe" regions were relatively spared. C_LIO_LIFindings were most pronounced in TLE-HS and ETLE groups, with distinct neuroanatomical profiles observed. C_LIO_LICortical thinning was associated with pronounced cerebellar volume loss in TLE-HS epilepsy, relative to controls. C_LI ETHICAL PUBLICATION STATEMENTWe confirm that we have read the Journals position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

neuroscience↗

bioRxiv2023

Origin and modern microbial ecology of secondary mineral deposits in Lehman Caves, Great Basin National Park, NV, USA

Lehman Caves is an extensively decorated, high desert cave that represents one of the main tourist attractions in Great Basin National Park, Nevada. Although traditionally considered a water table cave, recent studies identified abundant speleogenetic features consistent with a hypogenic and, potentially, sulfuric acid origin. Here, we characterized white mineral deposits in the Gypsum Annex (GA) passage to determine whether these secondary deposits represent biogenic minerals formed during sulfuric acid corrosion, and explored microbial communities associated with these and other mineral deposits throughout the cave. Powder X-ray diffraction (pXRD), scanning electron microscopy with electron dispersive spectroscopy (SEM-EDS), and electron microprobe analyses (EPMA) showed that, while most white mineral deposits from the GA contain gypsum, they also contain abundant calcite, silica, and other phases. Gypsum and carbonate-associated sulfate isotopic values of these deposits are variable, with {delta}34SV-CDT between +9.7{per thousand} and +26.1{per thousand}, and do not reflect depleted values typically associated with replacement gypsum formed during sulfuric acid speleogenesis. Petrographic observations show that the sulfates likely co-precipitated with carbonate and SiO2 phases. Taken together, these data suggest that the deposits resulted from later stage meteoric events and not during an initial episode of sulfuric acid speleogenesis. Most sedimentary and mineral deposits in Lehman Caves have very low microbial biomass, with the exception of select areas along the main tour route that have been impacted by tourist traffic. High-throughput 16S rRNA gene amplicon sequencing showed that microbial communities in GA sediments are distinct from those in other parts of the cave. The microbial communities that inhabit these oligotrophic secondary mineral deposits include OTUs related to known ammonia-oxidizing Nitrosococcales and Thaumarchaeota, as well as common soil taxa such as Acidobacteriota and Proteobacteria. This study reveals microbial and mineralogical diversity in a previously understudied cave and expands our understanding of the geomicrobiology of arid, hypogene cave systems.

microbiology↗

bioRxiv2023

Female-biased expressed odorant receptor genes differentially tuned to repulsive or attractive plant volatile compounds in the turnip moths

Insects rely on their highly efficient and precise olfactory systems to find suitable mates, host plants and oviposition sites, and adapt to the changing environment. The odorant receptors (ORs) including pheromone receptors (PRs) play a vital role in this process. While extensive studies have been focusing on deorphanization of lepidopteran PR genes, the information on the ligand profiles of general ORs is still sparse. In the present study, we identified a repertoire of 61 ORs including the co-receptor Orco from antennal and ovipositor transcriptomes of the turnip moth Agrotis segetum, which clustered in all the major lepidopteran OR clades. We characterized the function of eight female-biased expressed ORs in Xenopus oocytes and found three ORs differentially tuned to plant volatile compounds that might be repulsive or attractive to the moths. AsegOR13 was broadly tuned to a number of herbivore-induced plant volatiles (HIPVs) while AsegOR20 was specific to citral; AsegOR17 was narrowly tuned to the alcohols, isoamyl alcohol, pentanol and benzyl alcohol, that are potentially attractive to moths. The orthologues of the three ORs in other moth species seem to share the conserved function. Our results support the hypothesis that insects recognize their host plants mostly by detecting the mixture of ubiquitous compounds, instead of taxonomically characteristic host compounds. The combination of narrowly and broadly tuned ORs will ensure both the accuracy of the most important odor signals and the plasticity of the olfactory system to the changes in the environment.

neuroscience↗

bioRxiv2023

Compensatory growth and recovery of tissue cytoarchitecture after transient cartilage-specific cell death in foetal mouse limbs

A major question in developmental and regenerative biology is how organ size is controlled by progenitor cells. For example, while limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse foetal cartilage was repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states was delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death was over, chondroprogenitor differentiation was accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlated with, and was necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.

developmental biology↗

bioRxiv2023

Active maintenance of CD8+ T cell naivety through regulation of global genome architecture

The differentiation of naive CD8+ cytotoxic T lymphocytes (CTLs) into effector and memory states results in large scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organisation reflect or underpin these transcriptional programs. We utilised Hi-C to map changes in the spatial organisation of long-range genome contacts within naive, effector and memory virus-specific CD8+ T cells. We observed that the architecture of the naive CD8+ T cell genome was distinct from effector and memory genome configurations with extensive changes within discrete functional chromatin domains. However, deletion of the BACH2 or SATB1 transcription factors was sufficient to remodel the naive chromatin architecture and engage transcriptional programs characteristic of differentiated cells. This suggests that the chromatin architecture within naive CD8+ T cells is preconfigured to undergo autonomous remodelling upon activation, with key transcription factors restraining differentiation by actively enforcing the unique naive chromatin state. One Sentence SummaryCD8+ T cell naivety is actively maintained by transcription factors that enforce a distinct, naive chromatin architecture. HighlightsO_LICD8+ T cell differentiation states are underscored by distinct chromatin looping architectures. C_LIO_LIChromatin loops juxtapose CTL state appropriate enhancers, transcription factors and genes. C_LIO_LIEffector and memory CTLs have similar genome architectures, explaining rapid memory recall. C_LIO_LICTL differentiation is restrained by BACH2 and SATB1, which enforce a naive loop architecture. C_LI

immunology↗

bioRxiv2023

Nuclear Factor-Y is a Pervasive Regulator of Neuronal Gene Expression

Nervous system function relies on the establishment of complex gene expression programs that provide neuron-type-specific and core pan-neuronal features. These complementary regulatory paradigms are controlled by terminal selector and parallel-acting transcription factors (TFs), respectively. Here, we identify the Nuclear Factor Y (NF-Y) TF as a pervasive regulator of both neuron-type-specific and pan-neuronal gene expression. Mapping global NF-Y targets reveals direct binding to the cis-regulatory regions of pan-neuronal genes and terminal selector TFs. We show that NFYA-1 controls pan-neuronal gene expression directly through binding to CCAAT boxes in target gene promoters and indirectly by regulating the expression of terminal selector TFs. Further, we find that NFYA-1 regulation of neuronal gene expression is important for neuronal activity and motor function. Thus, our research sheds light on how global neuronal gene expression programs are buffered through direct and indirect regulatory mechanisms.

neuroscience↗

bioRxiv2022

Odorant receptor orthologues in conifer-feeding beetles display conserved responses to ecologically relevant odors

Insects are able to detect a plethora of olfactory cues using a divergent family of odorant receptors (ORs). Despite the divergent nature of this family, related species frequently express several evolutionarily conserved OR orthologues. In the largest order of insects, Coleoptera, it remains unknown whether OR orthologues have conserved or divergent functions in different species. Using HEK293 cells, we addressed this question through functional characterization of two groups of OR orthologues in three species of the Curculionidae (weevil) family, the conifer-feeding bark beetles Ips typographus L. ( Ityp) and Dendroctonus ponderosae Hopkins ( Dpon) (Scolytinae), and the pine weevil Hylobius abietis L. ( Habi; Molytinae). The ORs of H. abietis were annotated from antennal transcriptomes. Results show highly conserved response specificities, with one group of orthologues (HabiOR3/DponOR8/ItypOR6) responding exclusively to 2-phenylethanol (2-PE), and the other group (HabiOR4/DponOR9/ItypOR5) responding to angiosperm green leaf volatiles (GLVs). Both groups of orthologues belong to the coleopteran OR subfamily 2B, and share a common ancestor with OR5 in the cerambycid Megacyllene caryae, also tuned to 2-PE, suggesting a shared evolutionary history of 2-PE receptors across two beetle superfamilies. The detected compounds are ecologically relevant for conifer-feeding curculionids, and are probably linked to fitness, with GLVs being used to avoid angiosperm non-host plants, and 2-PE being important for intraspecific communication and/or playing a putative role in beetle-microbe symbioses. To our knowledge, this study is the first to reveal evolutionary conservation of OR functions across several beetle species and hence sheds new light on the functional evolution of insect ORs.

neuroscience↗

bioRxiv2021

Comparative genomics of Nocardia seriolae reveals recent importation and subsequent widespread dissemination in mariculture farms in South Central Coast, Vietnam

Between 2010 and 2015, nocardiosis outbreaks caused by Nocardia seriolae affected many permit farms throughout Vietnam, causing mass fish mortalities. To understand the biology, origin, and epidemiology of these outbreaks, 20 N. seriolae strains collected from farms in four provinces in the South-Central Coast of Vietnam, along with two Taiwanese strains, were analysed using genetics and genomics. Pulsed-field gel electrophoresis identified a single cluster amongst all Vietnamese strains that was distinct from the Taiwanese strains. Like the PFGE findings, phylogenomic and single-nucleotide polymorphism (SNP) genotyping analyses revealed that all Vietnamese N. seriolae strains belonged to a single, unique clade. Strains fell into two subclades that differed by 103 SNPs, with almost no diversity within clades (0-2 SNPs). There was no association between geographic origin and subclade placement, suggesting frequent N. seriolae transmission between Vietnamese mariculture facilities during the outbreaks. Vietnamese strains shared a common ancestor with strains from Japan and China, with the closest strain, UTF1 from Japan, differing by just 217 SNPs from the Vietnamese ancestral node. Draft Vietnamese genomes range from 7.55-7.96 Mbp in size, have an average G+C content of 68.2%, and encode 7,602-7,958 predicted genes. Several putative virulence factors were identified, including genes associated with host cell adhesion, invasion, intracellular survival, antibiotic and toxic compound resistance, and haemolysin biosynthesis. Our findings provide important new insights into N. seriolae epidemiology and pathogenicity and will aid future vaccine development and disease management strategies, with the ultimate goal of nocardiosis-free aquaculture.

genomics↗

bioRxiv2021

The epidemiology and genomics of a virulent emerging fungal pathogen in an Australian reptile

Emerging infectious fungal diseases (EIFDs) represent a major conservation concern worldwide. Here, we provide early insights into the potential threat that Nannizziopsis barbatae (Nb), a novel EIFD, poses to Australian herpetological biodiversity. First known to the reptile pet trade as a primary pathogen causing untreatable severe dermatomycosis, since 2013, Nb has emerged in a growing number of phylogenetically and ecologically distant free-living reptiles across Australia. Observing its emergence in a long-term study population of wild eastern water dragons (Intellagama lesueurii), we demonstrate the pathogens virulence-related genomic features, within-population spatiotemporal spread, and survival costs, all of which imply that Nb could pose a threat to Australian reptiles in the future. Our findings highlight the need to closely monitor this pathogen in Australian ecosystems.

ecology↗

bioRxiv2021

Genomic insights into variation in thermotolerance between hybridizing swordtail fishes

Understanding how organisms adapt to changing environments is a core focus of research in evolutionary biology. One common mechanism is adaptive introgression, which has received increasing attention as a potential route to rapid adaptation in populations struggling in the face of ecological change, particularly global climate change. However, hybridization can also result in deleterious genetic interactions that may limit the benefits of adaptive introgression. Here, we used a combination of genome-wide quantitative trait locus mapping and differential gene expression analyses between the swordtail fish species Xiphophorus malinche and X. birchmanni to study the consequences of hybridization on thermotolerance. While these two species are adapted to different thermal environments, we document a complicated architecture of thermotolerance in hybrids. We identify a region of the genome that contributes to reduced thermotolerance in individuals heterozygous for X. malinche and X. birchmanni ancestry, as well as widespread misexpression in hybrids of genes that respond to thermal stress in the parental species, particularly in the circadian clock pathway. We also show that a previously mapped hybrid incompatibility between X. malinche and X. birchmanni contributes to reduced thermotolerance in hybrids. Together, our results highlight the challenges of understanding the impact of hybridization on complex ecological traits and its potential impact on adaptive introgression.

evolutionary biology↗

bioRxiv2021

CRISPR screens identify gene targets and drug repositioning opportunities at breast cancer risk loci

Genome-wide association studies (GWAS) have identified >200 loci associated with breast cancer (BC) risk. The majority of candidate causal variants (CCVs) are in non-coding regions and are likely to modulate cancer risk by regulating gene expression. We recently developed a scoring system, INQUISIT, to predict candidate risk genes at BC-risk loci. Here, we used pooled CRISPR activation and suppression screens to validate INQUISIT predictions, and to define the cancer phenotypes they mediate. We measured proliferation in 2D, 3D, and in immune-deficient mice, as well as the effect on the DNA damage response. We performed 60 CRISPR screens and identified 21 high-confidence INQUISIT predictions that mediate a cancer phenotype. We validated the direct regulation of a subset of genes by BC-risk variants using HiCHIP and CRISPRqtl. Furthermore, we show the utility of expression profiling for drug repurposing against these targets. We provide a platform for identifying gene targets of risk variants, and lay a blueprint of interventions for BC risk reduction and treatment.

cancer biology↗

bioRxiv2021

The Aspartyl Protease Ddi1 Is Essential for Erythrocyte Invasion by the Malaria Parasite

Malaria pathology is caused by the exponential replication of Plasmodium parasites in the blood stream. The bottleneck of the parasite life cycle is the invasion of erythrocytes immediately after parasites egress from infected red blood cells. DNA damage-inducible protein 1 (Ddi1) is a conserved eukaryotic proteasome shuttle protein containing an internal retroviral-like protease domain. Using conditional genetics, we now show that the proteolytic activity of the P. falciparum homologue, PfDdi1, is critically required for invasion of red blood cells. Furthermore, PfDdi1 disruption results in the accumulation of highly polyubiquitinated proteins that can be processed by purified PfDdi1 or distant eukaryotic homologues. We also show that PfDdi1 interacts with multiple components of the ubiquitin-proteasome system and that parasites lacking PfDdi1 are more sensitive to proteasome inhibition. Overall, this study establishes PfDdi1 as a key component of the eukaryotic ubiquitin-proteasome system and as a promising antimalarial target.

cell biology↗

bioRxiv2021

Ionotropic receptors in the turnip moth Agrotis segetum respond to repellent medium-chain fatty acids

BackgroundIn insects, airborne chemical signals are mainly detected by two receptor families, odorant receptors (ORs) and ionotropic receptors (IRs). Functions of ORs have been intensively investigated in Diptera and Lepidoptera, while the functions and evolution of the more ancient IR family remain largely unexplored beyond Diptera. ResultsHere, we identified a repertoire of 26 IRs from transcriptomes of female and male antennae, and ovipositors in the moth Agrotis segetum. We observed that a large clade formed by IR75p and IR75q expansions is closely related to the acid-sensing IRs identified in Diptera. We functionally assayed each of the five AsegIRs from this clade using Xenopus oocytes and found that two receptors responded to the tested ligands. AsegIR75p.1 responded to several compounds but hexanoic acid was revealed to be the primary ligand, and AsegIR75q.1 responded primarily to octanoic acid, and less so to nonanoic acid. It has been reported that the C6-C10 medium-chain fatty acids repel various insects including many drosophilids and mosquitos. Our GC-EAD recordings showed that C6-C10 medium-chain fatty acids elicited antennal responses of both sexes of A. segetum, while only octanoic acid had repellent effect to the moths in a behavioural assay. In addition, using fluorescence in situ hybridization, we demonstrated that the five IRs and their co-receptor AsegIR8a are not located in coeloconic sensilla as found in Drosophila, but in basiconic or trichoid sensilla. ConclusionsOur results significantly expand the current knowledge of the insect IR family. Based on the functional data in combination with phylogenetic analysis, we propose that subfunctionalization after gene duplication plays an important role in the evolution of ligand specificities of the acid-sensing IRs in Lepidoptera.

evolutionary biology↗

bioRxiv2020

Genetic and pharmacological evidence for kinetic competition between alternative poly(A) sites in yeast

Most eukaryotic mRNAs accommodate alternative sites of poly(A) addition in the 3 untranslated region in order to regulate mRNA function. Here we present a systematic analysis of 3 end formation factors, which revealed 3UTR lengthening in response to a loss of the core machinery, whereas a loss of the Sen1 helicase resulted in shorter 3UTRs. We show that the anti-cancer drug cordycepin, 3 deoxyadenosine, caused nucleotide accumulation and the usage of distal poly(A) sites. Mycophenolic acid, a drug which reduces GTP levels and impairs RNA polymerase II (RNAP II) transcription elongation, promoted the usage of proximal sites and reversed the effects of cordycepin on alternative polyadenylation. Moreover, cordycepin mediated usage of distal sites was associated with a permissive chromatin template and was suppressed in the presence of an rpb1 mutation, which slows RNAP II elongation rate. We propose that alternative polyadenylation is governed by temporal coordination of RNAP II transcription and 3 end processing and controlled by the availability of 3 end factors, nucleotide levels and chromatin landscape.

cell biology↗

bioRxiv2020

A highly contiguous genome assembly of a major forest pest, the Eurasian spruce bark beetle Ips typographus

The Eurasian spruce bark beetle (Ips typographus [L.]), is a major killer of spruce forests across the Palearctic. During epidemics, it can destroy over 100 million cubic meters of spruce trees in a single year. Here we report a 236 Mb, highly contiguous I. typographus genome assembly using PacBio long-read sequencing. The final phased assembly had a contig N50 of 6.65 Mb in 272 contigs and was predicted to contain 23,923 protein-coding genes. Comparative genomic analysis revealed expanded gene families associated with plant cell wall degradation, including pectinases, aspartyl proteases, and glycosyl hydrolases. In todays forests, increasingly stressed by global warming, this resource can assist in mitigating bark beetle outbreaks by developing novel pest control strategies. Further, this first whole-genome sequence from the genus Ips provides timely resources to address important questions about the evolutionary biology and ecology of Curculionidae, the true weevils, one of the largest animal families.

genomics↗