Biology subjects

Lewis, D.

Publications and source records attributed to Lewis, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Beyond Single-Metric Assessments: Uncovering Masked Butterfly Declines via Multi-Scalar Analysis in Central Alberta

1. This study analyzed 21 years (2000-2025) of butterfly count data from Central Alberta, integrated with intensive 5-year (2021-2025) high-resolution intra-seasonal sampling. 2. Long-term macro-scale analysis revealed a significant decline in Shannon Diversity, a change that remained obscured when relying solely on traditional metrics of species richness and evenness. 3. This diversity decline was primarily driven by the severe, long-term collapse of the native Common Ringlet (Coenonympha tullia). 4. Four other dominant species--Cabbage White (Pieris rapae), Clouded Sulphur (Colias eriphyle), European Skipper (Thymelicus lineola), and Common Wood Nymph (Cercyonis pegala)--maintained long-term population stability, though their abundances were significantly constrained by extreme winter minimum temperatures and rapid spring warming. 5. High-resolution intra-seasonal analysis (2021-2025) demonstrated that community indices and species-specific abundances were strongly limited by daily weather, particularly wind velocity and temperature. 6. These findings illustrate that while traditional metrics like richness and evenness are fundamental to community ecology, they provide incomplete insights when applied in isolation; they are most effective when utilized as part of a complementary, multi-scalar framework. 7. This study highlights the necessity of coupling multi-decadal historical datasets with high-frequency, fine-scale sampling to accurately identify the mechanisms of community turnover that simpler metrics may overlook. 8. The results underscore the critical importance of standardized citizen science monitoring in quantifying environmental impacts and establishing conservation priorities for terrestrial insect groups.

ecology↗

bioRxiv2026

Microbial, dietary insect, and pathogen communities in fresh and decomposing guano of anthropic little brown bat (Myotis lucifugus) maternity colonies

The guano of insectivorous bats holds ecological information that can be assessed non-invasively to characterize the gut microbiome and diet, alongside environmental microbes and pathogens of conservation concern. Despite this potential, how guano communities change during decomposition remains understudied, particularly inside anthropic roosts rather than caves. In this study, guano from little brown bat (Myotis lucifugus) colonies was sampled monthly across the summer maternity season from three sites across two locations in Connecticut, USA, at fresh deposition and at 4, 8, and 12 weeks following deposition. Resolving these cross-kingdom signals required five workflows: short-read 16S and ITS2 amplicon sequencing (Illumina) for bacterial and fungal profiling, long-read CO1 metabarcoding (Oxford Nanopore) for arthropod diet in fresh samples, long-read shotgun metagenomics for viral identification in aged samples, and targeted qPCR for organisms of bat, human, and forest-health concern. Fresh guano generated a consistent bacterial signal across sites, whereas fresh fungal communities differed by site. Responses to decomposition depended on roost setting: exterior sites lost fungal diversity and shifted toward environmental aerobes over time, while the interior roost retained the fresh sample profile. Dietary composition varied temporally, was dominated by Diptera, and included the invasive emerald ash borer (Agrilus planipennis). Pseudogymnoascus destructans, the causal agent of white-nose syndrome, occurred in fresh and aged samples at all three sites but persisted for 12 weeks only at the interior roost, where antifungal bacterial taxa were depleted. Long-read shotgun metagenomics of aged guano recovered roughly 100 viral species, predominantly bacteriophages, alongside non-bacteriophage mastadenoviruses associated with humans, bats, and other mammals. These results show that anthropic structures influence the trajectory of guano microbiome succession, and that maternity colony guano enables non-invasive assessment of environmental pathogens, bat diet, and bacterial and fungal communities.

ecology↗

bioRxiv2026

Molecular Characterization of the Progressive Landscape of Depression

Major Depressive Disorder (MDD) frequently follows a recurrent trajectory of episodes and remissions, often culminating in treatment-resistance. Molecular differences defining state-specific changes during episode and remission have been explored. However, progressive differences--defined here as cross-sectional linear trends across clinical stages from first to recurrent episodes or remissions, reflecting increasing illness burden over time--remain poorly understood, limiting sustained therapeutic outcomes. Here, we analyzed RNA-seq data from postmortem sgACC to identify progressive differences across MDD episodes or remission relative to state-specific differences, using an integrative assessment of molecular and cellular specificity, genetic-risk, disease-comorbidity and potential therapeutic targets. Differential expression analysis showed greater overlap between progressive and state-specific differences during remission than episode. Pathway enrichment highlighted disruptions in extracellular-matrix pathways shared by state-specific and progressive episodes, while metabolic and catalytic pathways were restored during remission. Cell-type-specific analyses showed that progressive changes were linked to superficial-layer intra-telencephalic neurons, whereas state-specific changes were enriched in pyramidal neuron subtypes and deeper layer SST-positive interneurons. Genome-wide association-informed enrichment analysis further linked these transcriptomic changes to genetic risk factors and symptom dimensions. Anhedonia was associated with both state-specific episode and progressive-remission signatures, suggesting that it is a persistent trait-like feature of MDD. Finally, an integrative pharmacological analysis revealed shared molecular mechanisms between pro-disease and therapeutic targets, highlighting pleiotropic effects of key pathways depending on disease state and dosage. Together, these findings provide a novel perspective on biological underpinnings of MDD progression over episodes or remissions and identify pharmacological targets that account for pathological and/or compensatory/therapeutic processes.

neuroscience↗

bioRxiv2026

EffectorGeneP: accurate gene annotation in pathogen genomes from infection transcriptomes

Accurate gene annotation is crucial for inference of biological knowledge from genomes. However, non-canonical genes such as orphan or single-exon genes as well as those residing in rapidly evolving regions are routinely dismissed in annotation pipelines. In filamentous pathogen genomes, this disproportionately affects the annotation of genes encoding disease-promoting effector proteins. We introduce EffectorGeneP, a machine learning tool that self-trains on transcript data, predicts the most likely coding sequence from transcripts and effectively separates bona fide genes from transcriptional noise. EffectorGeneP annotates over 95% of known effectors correctly, while other state-of-the-art methods annotate 15%-78%. We show that EffectorGeneP expands the predicted secretome of pathogens by over 50% and that high-throughput screening of an effector library in plant protoplasts uncovers the previously poorly annotated AvrSr26 gene family in the wheat stem rust fungus. EffectorGeneP decodes genomes at unprecedented resolution and will enable the study of biological processes in important pathogen species.

microbiology↗

bioRxiv2026

Large increases in resistance training volume do not impair skeletal muscle hypertrophy or anabolic-catabolic molecular signalling in trained individuals

Skeletal muscle hypertrophy results from the integrated regulation of anabolic and proteolytic processes in response to mechanical loading. Although increases in resistance training (RT) volume are used to increase mechanical stress, it remains uncertain whether large and abrupt volume progressions could exceed muscle adaptive capacity by disrupting the balance between anabolic and catabolic signaling. The present study investigated whether a large increase in weekly RT volume (+120%) leads to impaired hypertrophic outcomes and intracellular regulatory responses compared with a modest increase (+20%). Twenty-five resistance-trained men and women (18-35 years old) completed an 8-week randomized, single-blind, within-subject unilateral intervention. Each participant trained both legs twice weekly, with one leg assigned to the large (VOL120) and the contralateral leg to the modest (VOL20) weekly volume progressions relative to habitual training volume. Vastus lateralis muscle cross-sectional area (mCSA) was assessed by ultrasonography before and after training. Muscle biopsies were obtained at baseline, post-intervention, and 24 h after the last session to quantify muscle fiber cross-sectional area (fCSA), satellite cell myonuclear content, and anabolic/catabolic signaling markers. Both protocols induced increases in mCSA over time (p<0.001), with no protocol vs. time interaction. No significant effects were observed for fCSA nor satellite cell number or myonuclear content. Additionally, molecular responses related to translational regulation and protein degradation were largely similar between protocols. Collectively, these data indicate that a large, abrupt increase in weekly set volume does not impair hypertrophic adaptations or meaningfully alter the anabolic-catabolic signaling profile in resistance-trained individuals.

physiology↗

bioRxiv2025

Detection of a novel Puccinia coronata f. sp. avenae genotypic lineage in Australia during the 2024 oat growing season

Crown rust, caused by Puccinia coronata f. sp. avenae (Pca), remains a persistent threat to oat production in Australia. To monitor recent shifts in virulence and population structure, 30 Pca isolates collected during the 2024 growing season across major Australian oat-producing regions were analysed. Virulence analysis of 30 isolates using 52 oat differential lines identified 25 unique races that were not detected in previous years. Whole-genome sequencing of 28 of these isolates were analysed in the context of a broader historical Australian and international genomic datasets including isolates from Taiwan, South Africa, USA. Results confirmed the uniqueness of the Australian Pca population and revealed well-established genotypic lineages persisting over multiple years, with L18 and L16 being dominant. Notably, L16 was again present in Western Australia after being undetected in 2023, while L18 maintained its prevalence for a third consecutive season. Beyond these dominant groups, phylogenetic analysis and a k-mer containment analysis also identified a novel and genetically distinct lineage, designated as L19, represented by one isolate collected in WA. To add to the characterisation of lineage L19, we recorded virulence phenotypes on a small collection of current commercial cultivars. These findings enhance understanding of Pca diversity and emphasise the importance of surveillance approaches that integrate phenotypic and genomic surveillance.

pathology↗

bioRxiv2025

Dehydrating microhabitats increase mite activity and intensify ectoparasitism of Drosophila

Parasites interact with their host in variable environments that are often subject to water scarcity and dehydration. Drosophila fruit flies and associated ectoparasitic mites interact across a range of microhabitats, typically in decaying organic matter, such as fallen fruit and cactus tissue, that dries out and deteriorates over periods ranging from days to months. Here, we report that mite parasitism of Drosophila increases with exposure to increasingly dry conditions for two fly-mite systems (D. nigrospiracula-Macrocheles and D. melanogaster-Gamasodes). In D. melanogaster, artificial selection for behavioral resistance did not eliminate this effect, as previously selected lines remained relatively more resistant than non-selected controls even under dry conditions. Water balance assays confirmed that mites became dehydrated when held under dry conditions, which was also associated with increased mite activity. Exposure of D. melanogaster to mites dehydrated by exposure to low relative humidity increased parasitism, further supporting that mite infestation intensifies under dry conditions. The results indicate that ectoparasitism in this system is affected by the water content of the mites. The increased motivation of mites to parasitise flies under dry conditions may serve to replenish mite water stores and facilitate dispersal to more favorable microhabitats.

physiology↗

bioRxiv2025

Haplotype-resolved genomes of diverse oat crown rust isolates reveal both global dispersion of long-lived clonal haplotypes and limited recombination between haplotypes.

Genetic diversity of pathogen populations plays an important role in host adaptation. While single high quality genome references are a valuable resource, a compilation of genome references from individuals increases the breadth of genetic variation within a species that is captured. Puccinia coronata f. sp. avenae (Pca), a fungal pathogen causing crown rust of oat, demonstrates rapid virulence evolution and adaptation to newly released cultivars. To broaden the geographic and temporal distribution of available Pca genomes, we generated nuclear haplotype-resolved genome references for ten isolates from Europe, Africa and the Middle East and compared these with existing references for USA and Australian isolates. Of the full collection of 52 haplotypes, 40 were unique. Importantly, the presence of a nearly identical haplotype in a UK isolate collected in 1984 and in USA isolates from 1990 and 2017 supports the existence of long-lived clonal haplotypes in the global population that have been exchanged between lineages. Taken together with the identification of infrequent recombination between haplotypes from geographically dispersed isolates, this evidence reflects a globally mobile population of Pca that is mostly comprised of persistent clonal lineages with some influence from rare recombination events. Analysis of the core and non-core proteome suggests that while the core proteome is enriched for predicted secreted and effector proteins, sequence and expression variation are most prevalent in non-core orthogroups. We anticipate that this expanded collection of haplotypes will facilitate the development of new surveillance technologies and identification of virulence loci.

genomics↗

bioRxiv2025

QTL mapping of oat crown rust resistance in Australian fields and identification of a seedling resistance locus in oat line GS7

The development of oat cultivars with resistance to crown rust caused by Puccinia coronata f. sp. Avenae (Pca) is key for sustainable disease control. This study examined two recombinant inbred line populations, Provena x GS7 and Boyer x GS7, to identify adult plant resistance QTL in Australian fields. Seven distinct QTL associated with rust resistance were identified, with KASP markers developed for single nucleotide polymorphisms (SNPs) tightly linked to the four most significant QTL on chromosomes 4A and 7A. A major QTL named QPc_GS7_4A.2 with a resistance allele derived from line GS7 was mapped to chromosome 4A, overlapping with genomic regions previously associated with both resistance gene Pc61 and adult plant resistance. Genetic mapping for rust resistance at seedling stage using a subset of Provena x GS7 lines with contrasting alleles at QPc_GS7_4A.2 confirmed the role of this locus on seedling resistance, likely by Pc61. Furthermore, we found similar resistance profiles between GS7 and the Pc61 differential line against 20 Pca isolates at the seedling stage. Haplotype analysis of QPc_GS7_4A.2 in the oat crown rust differential set and an oat collection revealed the resistance haplotype in lines previously postulated to carry resistance gene Pc61. These results suggest that the QTL QPc_GS7_4A.2 is closely linked to the Pc61 locus on chromosome 4A. The KASP markers associated with Pc61 and QTL identified in this study will be valuable tools, allowing breeders to efficiently integrate the resistance allele for gene combinations in new cultivars, particularly in regions where Pc61 remains effective.

plant biology↗

bioRxiv2025

Combining Machine Learning and Multiplexed, In Situ Profiling to Engineer Cell Type and Behavioral Specificity

A promising strategy for the precise control of neural circuits is to use cis-regulatory enhancers to drive transgene expression in specific cells. However, enhancer discovery faces key challenges: low in vivo success rates, species-specific differences in activity, challenges with multiplexing adeno-associated viruses (AAVs), and the lack of spatial detail from single-cell sequencing. In order to accelerate enhancer discovery for the dorsal spinal cord--a region critical for pain and itch processing--we developed an end-to-end platform, ESCargoT (Engineered Specificity of Cargo Transcription), combining machine learning (ML)-guided enhancer prioritization, modular AAV assembly, and multiplexed, in situ screening. Using cross-species chromatin accessibility data, we trained ML models to predict enhancer activity in oligodendrocytes and in 15 dorsal horn neuronal subtypes. We first demonstrated that an initial enhancer, Excit-1, targeted excitatory dorsal horn neurons and drove reversal of mechanical allodynia in an inflammatory pain model. To enable parallel profiling of a 27-enhancer-AAV library delivered intraspinally in mice, we developed a Spatial Parallel Reporter Assay (SPRA) by integrating a novel Golden-Gate assembly pipeline with multiplexed, in situ screening. Regression adjustment for spatial confounding enabled specificity comparisons between enhancers, demonstrating the ability to screen enhancers targeting diverse cell types (oligodendrocytes, motoneurons, dorsal neuron subtypes) in one experiment. We then validated two candidates, targeting Exc-LMO3 and Exc-SKOR2 neurons, respectively. In a companion paper by Noh et al, our colleagues show that the functional specificity of the Exc-SKOR2-targeting enhancer, unlike Excit-1, is capable of blocking the sensation of chemical itch in mice. These enhancers were derived from the macaque genome but displayed functional sensitivity in mice. This platform enables spatially resolved, multiplexed in vivo enhancer profiling to accelerate discovery of cell-targeting tools and gene therapy development.

neuroscience↗

bioRxiv2025

Sustained Glucose Turnover Flux Distinguishes Cancer Cachexia from Nutrient Limitation

Cancer cachexia is an involuntary weight loss condition characterized by systemic metabolic disorder. A comprehensive flux characterization of this condition however is lacking. Here, we systematically isotope traced eight major circulating nutrients in mice bearing cachectic C26 tumors (cxC26) and food intake-matched mice bearing non-cachectic C26 tumors (ncxC26). We found no difference in whole-body lipolysis and proteolysis, ketogenesis, or fatty acid and ketone oxidation by tissues between the two groups. In contrast, compared to ncxC26 mice ad libitum, glucose turnover flux decreased in food intake-controlled ncxC26 mice but not in cxC26 mice. Similarly, sustained glucose turnover flux was observed in two autochthonous cancer cachexia models despite reduced food intake. We identified glutamine and alanine as responsible for sustained glucose production and tissues with altered use of glucose and lactate in cxC26 mice. We provide a comprehensive view of metabolic alterations in cancer cachexia revealing those distinct from decreased nutrient intake. HighlightsO_LIQuantitative fluxomics of cancer cachexia under matched food intake and body weight C_LIO_LIIntact lipolysis, proteolysis, ketogenesis, and lipid oxidation in cachectic mice C_LIO_LISustained glucose consumption in cachectic mice despite reduced food intake C_LIO_LIIncreased glucose production from glutamine and alanine in cachectic mice C_LI

cancer biology↗

bioRxiv2025

Targeting of CIP4-Calcineurin Signalosomes Improves Cardiac Structure and Function After Myocardial Infarction

BackgroundCalcineurin in a pleiotropic signaling enzyme that promotes pathological cardiac remodeling but also cardioprotection in ischemia-reperfusion injury. In addition, calcineurin inhibitors are immunosuppressants. This pleiotropy has precluded the use of calcineurin inhibitors as treatments for heart failure. Cdc42-interacting protein 4 (CIP4/TRIP10) is an endosomal scaffold protein that organizes a calcium and calcineurin A{beta}2 (CaNA{beta}2) signaling compartment activated by G-protein coupled receptors independently of contractile calcium. CIP4 binds CaNA{beta}2 via the CaNA{beta}-specific N-terminal polyproline (PP) domain. We previously showed that targeting of CIP4-CaNA{beta}2 signalosomes inhibited pathological cardiac hypertrophy and the development of heart failure induced by chronic pressure overload in mice. It is unknown whether CIP4-CaNA{beta}2 signalosomes contribute to cardioprotection and/or cardiac remodeling in ischemic heart disease. MethodsCIP4 conditional knock-out (CKO) mice were studied by echocardiography with strain analysis and histology following ischemia-reperfusion (I/R) injury and permanent left coronary artery (LCA) ligation to induce myocardial infarction. Wildtype C57BL/6NJ mice were transduced with adeno-associated virus (AAV) engineered for cardiomyocyte-specific expression of either a CaNA{beta}2 shRNA to inhibit CaNA{beta}2 expression, a VIVIT peptide to inhibit CaN-NFAT signaling, or a CaNA{beta}2 PP peptide to block CIP4-CaNA{beta}2 binding. AAV-transduced mice were studied by I/R injury. Additional mice were subjected to permanent LCA ligation and subsequently treated with AAV to test the effects of CaN inhibition in chronic ischemic cardiomyopathy. The effects of CaNA{beta}2 PP-GFP expression on primary T-cell activation were studied in vitro. ResultsCIP4 CKO mice and mice expressing the PP anchoring disruptor peptide exhibited preserved cardiac function after I/R injury and decreased infarct size and preserved cardiac function 8 weeks after myocardial infarction by permanent LCA ligation. In contrast, cardiomyocyte-specific depletion of CaNA{beta}2 and VIVIT peptide expression worsened outcome after I/R injury and in chronic ischemic cardiomyopathy. In addition, in contrast to cardiomyocytes, PP-mediated CaNA{beta} anchoring inhibition had no effect on T-cell activation and cytokine expression in vitro. ConclusionsCIP4-CaNA{beta}2 signalosomes promote adverse cardiac remodeling and are not cardioprotective. Proof-of-concept is provided for the treatment of ischemic cardiomyopathy by a PP anchoring disruptor gene therapy. Targeting these complexes may be beneficial in cardiovascular diseases, including ischemic cardiomyopathy and acute myocardial infarction. Clinical PerspectiveO_ST_ABSWhat is New?C_ST_ABSO_LITargeting CIP4, which is a scaffold protein for the phosphatase calcineurin, improves cardiac function in mice after acute myocardial infarction due to ischemia-reperfusion injury and in chronic ischemic cardiomyopathy. C_LIO_LIGene therapy-based expression of a calcineurin A{beta}-derived polyproline peptide, which can compete CIP4-calcineurin binding, is beneficial in acute and chronic myocardial infarction. C_LI What Are the Clinical Implications?O_LIThis study establishes CIP4 signalosomes as a new drug target for the treatment of ischemia-reperfusion injury and chronic pathological cardiac remodeling. C_LIO_LIThis study provides proof-of-concept for a new gene therapy approach to treating acute myocardial infarction and chronic ischemic cardiomyopathy. C_LI

physiology↗

bioRxiv2025

A chromosome-scale genome assembly of the flax rust fungus reveals the two unusually large effector proteins, AvrM3 and AvrN

Rust fungi comprise thousands of species many of which cause disease on important crop plants. The flax rust fungus Melampsora lini has been a model species for the genetic dissection of plant immunity since the 1940s, however the highly fragmented and incomplete reference genome has so far hindered progress in effector gene discovery. Here, we generate a fully-phased, chromosome-scale assembly of the two nuclear genomes of M. lini strain CH5, resolving an additional 320 Mbp of sequence compared to the previous short-read assembly. The 482 Mbp dikaryotic genome is at least 79% repetitive with a large proportion ([~]40%) of the genome comprised of young, highly similar transposable elements. The assembly resolves the known effector gene loci some of which carry complex duplications that were collapsed in the previous assembly. Using a genetic map followed by manual correction of gene models, we identify the AvrM3 and AvrN genes which encode unusually large fungal effector proteins and trigger defense responses when co-expressed with the corresponding resistance genes in Nicotiana tabacum. We locate the genes linked to the tetrapolar mating system on chromosomes 4 and 9, but in contrast to the cereal rusts which have one pheromone receptor gene per haplotype, in flax rust three pheromone receptor genes are found with two of them closely linked on one haplotype. Taken together, we show that a high-quality assembly is crucial for resolving complex gene loci and given the increasing number of fungal effectors of large size, the commonly applied criterion for effector candidates as being small proteins as needs to be reconsidered.

microbiology↗

bioRxiv2024

Identification of diagnostic KASP markers for selection of crown rust resistance in oats

Oat crown rust, caused by Puccinia coronata f. sp. avenae, poses a significant threat to global oat production (Avena sativa L.). Molecular markers are essential to assist in the integration of multiple resistance genes into a single oat cultivar to achieve genetic resistance durability. Here, we validated previously reported markers for the race-specific resistance genes Pc39, Pc45/PcKM, Pc54, and Pc68, and developed new KASP markers closely linked to these loci. These markers were subsequently screened across a collection of 150 oat cultivars. Analysis of molecular marker data, pedigree information, and disease resistance profile indicated several oat cultivars likely carrying Pc39 and Pc68. Newly identified carriers of Pc68 include the cultivars Galileo and Graza80, while Warrego, Kowari, Possum, Forester, Drummond, Hokonui, Glider, and Culgoa were identified as potential carriers of Pc39. Discrepancies between the previous postulation of Pc gene carriers and our phenotyping and genotyping analysis were also found. For example, the oat line Glider was previously postulated to carry Pc58 or Pc59, but it was positive for the Pc39-associated marker and had a similar resistance profile to Pc39 carriers. These findings underscore the importance of the utilisation of molecular markers in tracking the resistance genes in breeding germplasm. Key messageThis study has developed and validated KASP molecular markers associated with crown rust resistance genes Pc39, Pc45/PcKM, Pc54, and Pc68 that could be used for marker-assisted selection in oats.

genetics↗

bioRxiv2024

A high-resolution haplotype pangenome uncovers somatic hybridization, recombination and intercontinental migration in oat crown rust

Basidiomycetes like rust fungi have complex reproductive cycles and dikaryotic life stages which influence their population structure and evolution. Puccinia coronata f. sp. avenae (Pca), the causal agent of oat crown rust, is a pathogen of global economic importance. To investigate the genetic diversity of the species, as well as the role of mating type system and nuclear exchange (somatic hybridization) in host adaptation of Pca we acquired whole genome sequencing data of Taiwanese and Australian isolates, adding to existing data for USA and South African populations. An atlas of 30 chromosome-level, fully-phased nuclear haplotypes from six USA isolates and nine Australian isolates was generated to capture the genomic composition of key oat crown rust lineages. This study provides evidence of nuclear exchange and recombination of haplotypes in both the USA and Australian Pca populations as mechanisms for the introduction of genetic diversity. The limitations of assuming clonal evolutionary history from virulence phenotyping is demonstrated by the detection of either sexual or cryptic genetic recombination in the Pca Australian population. Overall, the characterization of intercontinental migration of Pca at the haplotype level provides further impetus for molecular monitoring of rust pathogen populations on a global scale.

genomics↗

bioRxiv2023

Shifted levels of sleep and activity under darkness as mechanisms underlying ectoparasite resistance

Parasites harm host fitness and are pervasive agents of natural selection capable of driving the evolution of host resistance traits. Indeed, host resistance in natural populations typically shows ample genetic variation, which may be maintained when parasite resistance imposes fitness costs on the host in the absence of parasites. Previously we demonstrated significant evolutionary responses to artificial selection for increasing behavioral immunity to Gamasodes queenslandicus mites in replicate lines of Drosophila melanogaster. Here, we report transcriptional shifts in metabolic processes between selected and control fly lines based on RNA-seq analyses. We also show decreased starvation resistance and increased use of nutrient reserves in flies from mite-resistant lines. Additionally, resistant lines exhibited increased behavioral activity, reduced sleep, and elevated oxygen consumption under conditions of darkness. Using an independent panel of D. melanogaster genetic lines exhibiting variable sleep durations, we found a positive correlation between mite resistance and reduced sleep, providing additional support for a link between resistance and sleep. Experimentally restraining the activity of artificially selected mite-resistant flies during exposure to parasites under dark conditions reduced their resistance advantage relative to control flies. The results suggest that ectoparasite resistance in this system involves increased dark-condition activity and metabolic gene expression at the expense of nutrient reserves and starvation resistance. Significance statementParasites are potent agents of selection, yet resistance may often be constrained evolutionarily because of trade-offs involving other fitness-related traits. Using artificial selection, we show that resistance to ectoparasites directly increases metabolism and decreases starvation resistance, predominantly through altered sleep and activity patterns at night. These studies highlight that active-resting patterns of the host are a significant driving force in ectoparasite resistance, but may have a negative impact on fitness during periods of low food availability. Our strongly integrative work suggests that parasite pressure may influence the evolution of host sleep and activity patterns.

evolutionary biology↗

bioRxiv2022

Extensive somatic nuclear exchanges shape global populations of the wheat leaf rust pathogen Puccinia triticina

Non-sexual processes such as somatic nuclear exchange are postulated to play a role in the diversity of clonally reproducing dikaryotic rust fungi but have been difficult to detect due to the lack of genome resolution between the two haploid nuclei. We examined three nuclear-phased genome assemblies of Puccinia triticina, which causes wheat leaf rust disease. We found that the most recently emerged Australian lineage is derived by nuclear exchange between two pre-existing lineages, which originated in Europe and North America. Haplotype-specific phylogenetic analysis reveal that repeated somatic exchange events have shuffled haploid nuclei between long-term clonal lineages, leading to a global population representing different combinations of a limited number of haploid genomes. Thus, nuclear exchange seems to be the predominant mechanism generating diversity and the emergence of new strains in this otherwise clonal pathogen. Such genomics-accelerated surveillance of pathogen evolution paves the way for more accurate global disease monitoring.

genomics↗

bioRxiv2022

Cellular and Molecular Organization of the Rhesus Macaque Dorsal Horn with a Comparison to Mouse

Key mechanisms underlying chronic pain occur within the neural circuitry of the dorsal horn. Recent genome-wide association studies (GWAS) have identified genetic variants associated with the predisposition to chronic pain. However, most of these variants lie in regulatory non-coding regions that have so far not been linked to spinal cord function. Here, we take a multi-species approach to determine whether chronic pain variants impact regulatory elements of dorsal horn neurons. We first built a more comprehensive single cell atlas; filling gaps by generating a high-quality Rhesus macaque atlas and integrating it with human and mouse. With cellular-resolution spatial transcriptomics, we mapped the laminar distributions of the resulting species-conserved neuron subtypes, uncovering an unexpected organization. Lastly, we generated a mouse single-nucleus open chromatin atlas to partition the heritability of chronic pain traits. From this, we identified strong, selective associations between specific, conserved neuron subtypes and major forms of chronic pain.

neuroscience↗