Biology subjects

Clark, A. G.

Publications and source records attributed to Clark, A. G..

At least 19 recordsLinked to original sources

bioRxiv2026

No detectable effect of P2 neurons on female post-mating changes in sleep and feeding in Drosophila melanogaster

In many insects, females exhibit behavioral changes after mating. This plasticity can be mediated by interactions between male-derived seminal fluid proteins (SFPs) and the female nervous system. The Drosophila melanogaster seminal fluid protein Sex Peptide (SP) causes mated females to sleep less during the day and consume more food than unmated females, among other behavioral changes. Although the SP-sensing neural circuits that convey information to the females brain are known, the downstream neurons that affect post-mating behaviors remain unknown. P2 neurons in the flys central brain are good candidates for regulating post-mating changes in sleep and food consumption, as they express feeding- and sleep-responsive neuropeptide F (NPF), directly innervate the flys sleep center (the dorsal fan-shaped body, dFB), and are responsible for social-isolation-induced changes in sleep and food consumption. Using the GAL4/UAS system, we activated or silenced P2 neurons in mated and unmated females. We measured sleep duration using Drosophila Activity Monitors (DAM) and food consumption using Capillary Feeder (CAFE) and blue-dye assays. We found that P2-neurons are not responsible for post-mating changes in sleep and food consumption: mated females slept less during the day and ate more compared to unmated females irrespective of P2 neuron perturbation. Together, these results indicate that P2 neurons are unlikely to be primary downstream neurons through which male-transferred SP regulates post-mating sleep and food consumption. Future studies could determine whether P2 neurons regulate other post-mating behaviors or modulate sleep and feeding behaviors in a context-dependent manner.

genetics↗

bioRxiv2026

Cross-Kingdom Control: Yeast Prion Protein Modulates Host Physiology in Drosophila

Prions, once mainly studied for their pathogenic roles, are now gaining recognition as adaptive elements in microbial physiology. Over one-third of wild yeast isolates harbor prion proteins, yet their impact on host-microbe interactions remains poorly characterized. Given the ecological dominance of yeasts in the Drosophila mycobiome, we leveraged the Drosophila melanogaster-Saccharomyces cerevisiae system to investigate how the mycobiome-derived prion, [MRPL10+], modulates host physiology. We show that flies exposed to [MRPL10+] yeast exhibit significantly enhanced cold tolerance and increased locomotor activity. This effect persists with heat-killed yeast and diluted culture, suggesting a stable, potent bioactive factor. Using the genetically diverse Drosophila Global Diversity Lines (GDL), we identified natural variation in responsiveness to [MRPL10+] yeast. Genome-wide association and functional RNAi screening revealed a gut-brain signaling axis involving genes critical for digestion, intercellular communication, transcription regulation, and neural transmission. Notably, serotonin and octopamine pathways were essential for [MRPL10+]-induced changes in cold tolerance and locomotion, implicating neuromodulatory circuits in prion-mediated microbial signaling. Our findings establish a mechanistic link between a fungal prion and host metabolic and neural adaptation. This work provides the first genetic dissection of a prion-mediated host-microbe interaction, laying the groundwork for investigating beneficial prions in complex microbial communities and highlighting a new dimension of the mycobiomes influence on animal physiology.

evolutionary biology↗

bioRxiv2026

piRNA loss unleashes episodic transposition bursts

In Metazoa, transposon expression is suppressed by the piRNA pathway, and disruption of this pathway leads to rampant transposon expression. However, it remains unclear whether increased transposon expression results in actual transposition, and if so, which and how frequently transposons mobilize upon piRNA loss. Here, we developed a framework to track transposon copy accumulation across generations on a single set of nonrecombining haploid genome in the Drosophila male germline, with or without the piRNA biogenesis factor HP1D/Rhino. Single-fly Nanopore DNA sequencing revealed that multiple transposon families mobilized after 10-45 generations of piRNA loss. Among them, the most prolific across all replicates was copia, producing dozens of new insertions that were distributed across chromosome arms. With genomic DNA collected at every generation, we validated and dated each copia insertion, revealing episodic bursts of transposition that deviated strongly from a Poisson process. Using phylogenetic analysis, we further showed that multiple copia loci--both autonomous and nonautonomous copies--can mobilize. Interestingly, two additional transposon families, mdg3 and invader3, also mobilized episodically, but with distinct timing and magnitude, highlighting the stochastic nature of transposition bursts. Because we did not observe a single transposition event for these elements in controls, our results provide direct evidence that the piRNA pathway tightly suppresses germline transposition. More importantly, our findings argue that disruption of the piRNA pathway does not simply elevate transposition rates, but it instead unleashes punctuated and stochastic bursts of transposon movement that may radically reshape the timing and magnitude of mutational input during evolution.

genetics↗

bioRxiv2026

Application of the Bradley-Terry model to quantify components of sperm competition

In many species with female sperm storage, ejaculates from multiple males overlap in the female reproductive tract, making sperm competitive ability a key component of male reproductive fitness and a target of rapid evolutionary change in the underlying genes. Here, we used controlled laboratory assays of Drosophila melanogaster sperm competition, with doubly-mated females and paternity assignment of offspring, to ask whether a Bradley-Terry framework can effectively summarize and predict competitive outcomes. The Bradley-Terry model is a probabilistic approach that estimates a latent "ability" score for each contestant based on outcomes of pairwise contests, and thus is naturally suited to data from sperm competition, which are intrinsically pairwise. We selected five distinct male genotypes: four carried strongly expressed RFP or GFP markers that allowed us to distinguish their heterozygous offspring under UV illumination, and the fifth was Canton-S, a standard wild-type genotype that served as our reference. Using Canton-S females, we assayed all 20 ordered pairwise combinations of first and second male, recorded successful double matings, and quantified the offspring sired by each male. We then extended the Bradley-Terry model to estimate genotype-specific competitive success separately for first-male "defense" (fertilization success following initial mating, also called "P1") and second-male "offense" (fertilization success following a remating, also called "P2"). This framework provides a flexible and efficient way to integrate results across large arrays of pairwise mating tests and to derive predictive scores for sperm competitive performance.

evolutionary biology↗

bioRxiv2026

Female genetic variation controlling timing of mating plug ejection in Drosophila melanogaster

In multiply-mating species, male-female postcopulatory, prezygotic interactions can influence reproductive outcomes. In Drosophila melanogaster, females can bias sperm storage and usage and thereby influence paternity outcomes. One mechanism by which females may regulate paternity contributions from specific males is through modulation of mating plug ejection timing. The D. melanogaster mating plug is composed of seminal fluid proteins, and some female-derived proteins, that coagulate in the female reproductive tract during mating. The mating plug facilitates sperm storage; thus, timing of female mating plug ejection is associated with sperm storage and relative paternity contributions in cases of multiple mating. However, whether there is natural genetic variation among females that shapes mating plug ejection timing, and genes or phenomena that might mediate it are unknown. We examined mating plug ejection in females from 69 lines of the Drosophila Genetic Reference Panel and observed dramatic differences in median plug ejection timing ranging from less than 1 to over 6 hours. We used this variation to perform a genome-wide association study to identify gene candidates associated with this phenotype. Many gene candidates are expressed in the brain and/or function in neurodevelopment. The candidate pool was also enriched for genes expressed in the ovary and functioning in oogenesis, indicating a link between female reproductive physiology and mating plug ejection. Consistent with this interpretation, females without a germline delay mating plug ejection. Our results demonstrate that female mating plug ejection is a physiologically integrated reproductive trait with a genetic basis that can be shaped by selection. Article SummaryThe D. melanogaster mating plug is composed of seminal fluid proteins and some female-derived proteins that coagulate in the female reproductive tract during mating. The mating plug facilitates sperm storage; thus, timing of female mating plug ejection is associated with sperm storage and relative paternity contributions in cases of multiple mating. Using the DGRP, we observed heritable genetic variation in female timing of mating plug ejection and through a GWAS find associated gene candidates. Gene candidates are enriched for neurodevelopment function and oogenesis function. We experimentally validate the connection between female mating plug ejection and the ovary.

genetics↗

bioRxiv2026

Interplay between β-catenin transcriptional and cell-cell junction activity regulates homeostasis and collective dynamics in the intestinal epithelium

Wnt signaling is crucial for stem cell maintenance during development and homeostasis, and its dysregulation is implicated in cancers across multiple tissues. {beta}-catenin, the primary mediator of canonical Wnt signaling, is also a crucial adaptor protein at cell-cell junctions and is required for maintaining tissue integrity. How the interplay and potential competition between these discrete functions of {beta}-catenin influences tissue homeostasis and organization is not well understood. Here, we address this open question in the intestinal epithelium, which is highly dependent on Wnt signaling during homeostasis and regeneration. Ectopic activation of Wnt signaling in intestinal organoids by pharmacological or genetic perturbation leads to tissue fluidification and loss of epithelial integrity, while disrupting Wnt activity perturbs intracellular {beta}-catenin localization and dynamics at cell-cell junctions. Stabilization of cell-cell junctions increases {beta}-catenin accumulation at junctions at the expense of nuclear localization, while junctional perturbation leads to {beta}-catenin release from junctions into the cytoplasm, leading to dysregulation of Wnt signaling. Together, our findings indicate that in tissues with active Wnt signaling, the interplay between junction- and signaling-associated {beta}-catenin is crucial for stem cell regulation and tissue homeostasis.

cell biology↗

bioRxiv2026

Reconstituting organotypic 2D microtissue co-cultures via sequential stenciling

In mammalian organisms, native tissue function depends on precise spatial organization down to the cellular level. Reconstituting tissue architectures in 2D in vitro platforms can provide a means to study direct and indirect cell-cell interactions in a variety of tissue contexts while remaining compatible with high-throughput assays and high-resolution live imaging. We combine cost-effective stereolithography leveraging 3D printing with replica molding to stencil spatially defined, multicellular culture systems with sub-millimeter resolution onto planar substrates. The system is designed for ease of use, requires no complex fabrication setups and scales readily to 96-well plates. Sequential stencil application and removal under a biosafety cabinet enables controlled positioning of multiple cell types and supported the maturation of tissue assemblies. We demonstrate the utility of this stencil-based patterning strategy in three applications. First, we employ a combination of two circular stencils to recreate a structural feature characteristic for the tumor microenvironment of solid tumors: the encapsulation of colorectal cancer cells by cancer-associated fibroblasts. Resulting cell patternings reproduce native tissue dynamics of the densely packed tumor tissues, in which cancer-associated fibroblast cells actively compress the cancer cells and confer targeted therapy resistance. Second, we probe the synthetic, diffusible morphogen system synNotch in patterned cell patches, where GFP-releasing cells generate a ligand-dependent gradient. Third, we recapitulate the characteristic crypt-villus architecture of the mammalian intestine by patterning intestinal organoids within a stencil-restricted crypt region and allowing differentiating cells to collectively migrate along a designed villus axis. The presented strategy allows for rebuilding multicellular tissue architectures in vitro with biologically relevant spatial precision for high-throughput drug screenings and dissection of tissue-specific cellular interactions.

bioengineering↗

bioRxiv2026

Mechanosensing and IL-13 Signaling Synergistically Modulate Intestinal Stem Cell Differentiation via STAT6 and YAP

A long-term complication of chronic inflammation is the mechanical stiffening of the tissue, culminating in fibrosis. Fibrosis can severely disrupt tissue function and is a major risk factor for other diseases. It is not currently well understood how fibrosis impacts the response to inflammatory signals. To address this, we investigated cross-talk between cellular mechanosensing and the response to Interleukin (IL)-13, a cytokine associated with inflammatory bowel diseases (IBDs). Using 3D intestinal organoids and organoid monolayer culture, we uncovered a synergy between mechanosensing and IL-13 signaling in regulating intestinal stem cell differentiation. Through quantitative high-resolution microscopy and functional inhibition, we found that this response requires activation of STAT6, a known mediator of IL-13. Both IL-13 and high substrate stiffness increase cellular traction forces and focal adhesion formation, but at the expense of reduced tension at cell-cell junctions and compromised epithelial barrier function. The mechanosensing and IL-13 responses require actomyosin contractility and YAP, which is activated downstream of a positive feedback loop involving STAT6-dependent myosin-2 activation. Our results establish a novel STAT6-YAP signaling axis that integrates inflammatory and mechanical cues to regulate intestinal cell fate and barrier integrity, opening new avenues to target epithelial dysfunction in fibrosis, chronic inflammation and regenerative medicine.

cell biology↗

bioRxiv2025

Correlated Gene Copy Number Changes in a Seminal Fluid Protein Network in Drosophila

Reproductive proteins often diverge rapidly between species, yet network function must be maintained. Shared selective pressures on network members and compensatory changes between members can drive their parallel evolutionary trajectories. Indeed, correlated evolutionary rates of amino acid sequence change have been observed for interacting reproductive proteins. But whether gene copy number changes also correlate has not been widely studied. Here, we investigated copy number variation (CNV) of genes in the Drosophila Sex Peptide Seminal Fluid Protein (Sfp) network. Previous research analyzed CNV of the Sfp Sex Peptide (SP) in Drosophila species. We focus on 9 other Sfps whose function is required to mediate the binding of SP to sperm in D. melanogaster which is required for persistence of female post-mating responses. To exhaustively annotate CNV of genes, we developed a computational pipeline pairing iterative protein queries to genome sequence searches with phylogenetic clustering to resolve homology relationships. We observed that the Sfp networks genes are ancestral to Drosophila and that there were repeated duplications and losses of network members across the genus. We detect statistically significant correlations in gene duplication or loss events among network proteins, and show this can be used to identify new members of the network. We also investigated CNV of female-derived proteins that act downstream of the SP sperm-binding network to modulate SP function, these proteins showed no significant correlation of gene turnover events with SP or its network. Our results provide insight into how evolving reproductive genes tolerate duplication and loss, and how network relationships could constrain reproductive protein evolution. Significance StatementReproductive proteins often diverge rapidly between species, yet network function must be maintained. Shared selective pressures on network members and compensatory changes between members can drive their parallel evolutionary trajectories. We report correlated gene duplication and loss among members of the Drosophila Sex Peptide seminal fluid protein network, suggesting that duplication or loss events may drive corresponding events in other network genes. This work is a natural extension of the idea of evolutionary rate covariation, but instead of scoring rates of substitution it tracks correlated duplication and loss events on the phylogeny. Applied to the Sex Peptide network, the method reveals striking patterns, especially for coordinated loss, and identifies a new network gene that is experimentally confirmed.

evolutionary biology↗

bioRxiv2025

The Stellate meiotic drive system of Drosophila melanogaster is active in contemporary populations

Meiotic drivers are selfish elements that bias their own transmission so that they are overrepresented among the functional gametes produced. The selective costs imposed by drivers on their hosts may trigger intragenomic conflict, promoting the evolution of suppressors and fueling an ongoing arms race between drivers and suppressors. Stellate (Ste) is an X-linked tandemly arrayed multicopy gene. Its copy number ranges from 3 to more than 300 among Drosophila melanogaster strains from the Global Diversity Lines. In wild-type animals, Ste expression is usually suppressed by homologous piRNAs produced from the Suppressor of Stellate (Su(Ste)) array on the Y chromosome. Derepression of Ste in the absence of Su(Ste) results in the formation of proteinaceous crystals in spermatocytes, chromatin compaction defects, reductions in fertility, and female-biased sex ratios arising from under-recovery of Y-bearing sperm. Despite extensive study, the function of the Stellate array and evolutionary significance of its persistence in the genome have remained elusive. It has been suggested to be a now-inactive relic of an ancient meiotic drive system, as perturbations in lab stocks can produce Ste-mediated meiotic distortions. Meiotic drive occurring among natural variants, however, has not been reported. We established crosses between females with high Ste copy number X chromosomes and males carrying low Su(Ste) copy number Y chromosomes and found that the male progeny displayed non-Mendelian sex chromosome transmission. Importantly, deletion of the euSte array in an otherwise matched genetic background rescues this phenotype, demonstrating that Stellate is an active driver in contemporary populations.

evolutionary biology↗

bioRxiv2025

Comparative population genomics reveals adaptive convergence in two Drosophila species across global environments

The extent to which evolution is predictable across lineages remains unclear. To address this question, we investigated convergent adaptation in a pair of globally distributed sibling species, Drosophila melanogaster and D. simulans. We integrated whole-genome data from approximately 2,000 strains sampled across major continents, and revealed a more recent global colonization of D. simulans relative to D. melanogaster. Using a suite of complementary selection scans, we quantified signatures of positive selection across evolutionary timescales and genomic contexts. Despite substantial divergence, approximately 9-13% of adaptively evolving genes were shared between species across methods, revealing widespread convergence at the gene and pathway levels. Convergence was particularly pronounced for insecticide resistance genes, and was also evident in oxidative stress experiment. This study provides a quantitative, multiscale framework for dissecting molecular convergence, offering insights into the predictability of evolution, the constraints imposed by genomic architecture, and the dynamics of adaptation under global environmental change.

evolutionary biology↗

bioRxiv2025

The regulatory landscape of nascent transcription in human health and disease

Transcriptional regulatory elements (TREs) orchestrate gene expression programs fundamental to cellular identity and transitions across physiological and pathological states. Here, we present a high-resolution atlas of RNA Polymerase II-engaged TREs (enhancers and promoters) across all major human organ systems and a broad spectrum of developmental and disease states. This atlas is generated using PRO-cap, a highly sensitive method that detects nascent RNA at transcription initiation sites, a critical feature of active TREs. The base-pair resolution of PRO-cap enables systematic dissection of transcription initiation architecture, revealing associations among tissue specificity, evolutionary constraint, transcription factor usage, and regulatory connectivity. Integration with deep learning models such as ProCapNet further provides a framework for prioritizing noncoding variants from GWAS and eQTL studies. Moreover, this tissue-resolved atlas identifies lineage-specific regulatory programs and their alterations in diseases such as metastatic cancer, where TRE landscapes capture regulatory signatures reflecting both tissue of origin and adaptive responses to distant niches. Together, these findings establish transcription initiation at regulatory elements as a defining and mechanistically informative layer of gene regulation across development, physiology, and disease.

genomics↗

bioRxiv2025

Genome-wide associations of fitness components reveal antagonistic pleiotropy and sexual conflict in the Florida Scrub-Jay

Natural populations often exhibit substantial genetic variation in fitness-related traits, providing the raw material for adaptation. The persistence of high levels of genetic variation in the presence of genetic drift and directional selection has long puzzled evolutionary biologists1-3. Recent studies suggest that antagonistic pleiotropy may play a greater role than previously appreciated, highlighting the need for more empirical studies that consider both sexual antagonism and life-history trade-offs4. Here, we performed a comprehensive assessment of fitness trade-offs within and between sexes in an extensively monitored natural population of Florida Scrub-Jays (Aphelocoma coerulescens)5. We found significant additive genetic variance for female fitness and identified several loci associated with variation in survival, fecundity, and lifetime reproductive success. Many loci associated with multiple fitness components had antagonistic effects, particularly within males. Considering genome-wide polygenic effects, we found multiple genetic trade-offs both within and between sexes, especially when considering different fitness components between sexes. Comparing allele frequency trajectories for putatively pleiotropic loci demonstrated that antagonistic SNPs had smaller allele frequency changes than concordant SNPs. Our fine-scale dissection of fitness components reveals substantial antagonistic pleiotropy that affects short-term evolution, highlighting the importance of antagonistic selection in maintaining genetic variation over short time scales in nature.

evolutionary biology↗

bioRxiv2025

Bayesian phylodynamic inference of population dynamics with dormancy

Many organisms employ reversible dormancy, or seedbank, in response to environmental fluctuations. This life-history strategy alters fundamental eco-evolutionary forces, leading to distinct patterns of genetic diversity. Two models of dormancy have been proposed based on the average duration of dormancy relative to coalescent timescales: weak seedbank, induced by scheduled seasonality (e.g., plants, invertebrates), and strong seedbank, where individuals stochastically switch between active and dormant states (e.g., bacteria, fungi). The weak seedbank coalescent is statistically equivalent to the Kingman coalescent with a scaled mutation rate, allowing the use of existing inference methods. In contrast, the strong seedbank coalescent differs fundamentally, as only active lineages can coalesce, while dormant lineages cannot. Additionally, dormant individuals typically mutate at a slower rate than active ones. Consequently, despite the significant role of dormancy in the eco-evolutionary dynamics of many organisms, no methods currently exist for inferring population dynamics involving dormancy and associated parameters. We present a Bayesian framework for jointly inferring a latent genealogy, seedbank parameters, and evolutionary parameters from molecular sequence data under the strong seedbank coalescent. We derive the exact probability density of genealogies sampled under the strong seedbank coalescent, characterize the corresponding likelihood function, and present efficient computational algorithms for its evaluation based on our theoretical framework. We develop a tailored Markov chain Monte Carlo sampler and implement our inference framework as a package SeedbankTree within BEAST2. Our work provides both a theoretical foundation and practical inference framework for studying the population genetic and genealogical impacts of dormancy.

evolutionary biology↗

bioRxiv2024

Directionality of Transcriptional Regulatory Elements

Divergent transcription is a critical marker of active transcriptional regulatory elements (TREs), including enhancers and promoters, in mammals. However, distal elements with unidirectional transcriptional patterns are often overlooked, leaving their identity and function poorly understood. Here, we performed a systematic comparison between divergent and unidirectional elements, revealing their distinct architectural and functional features. Our analysis also shows that unidirectional elements have younger sequence ages and are under weaker evolutionary constraints than divergent elements, indicating that they may represent a unique category of genomic regulatory function with more recent origins. Notably, we observed that some transcription factors, including CTCF, AP1, SP, and NFY, exhibit dual roles in modulating the directionality of TREs, either activating or repressing nascent transcription in a position-dependent manner. Overall, the elucidation of directionality enhances our understanding of the diverse architectural models, functional features, evolutionary dynamics, and regulatory logic of TREs.

molecular biology↗

bioRxiv2024

Whole-genome sequencing across space and time reveals impact of population decline and reduced gene flow in Florida Scrub-Jays

Whole-genome sequence data is proving to be highly informative about the past demography of free-living populations, and in the context of endangered species, it can provide a quantification of the genetic risk posed by reduced genetic diversity and inbreeding. Prior to 1920, the Florida scrub-jay (Aphelocoma coerulescens) had been widespread across Florida, but with the expansion of agriculture and human habitation, its population has declined by 95%, resulting in fragmentation into semi-isolated subpopulations. By sequencing 241 individuals sampled from five different regions and across two time points, this study quantifies a greater magnitude of loss of genetic diversity and greater levels of inbreeding in smaller and more isolated subpopulations. Consistent with population genetics theory, reduction in population size results in a dramatic loss of rare alleles, skewing the site frequency spectrum far from the expected equilibrium. Increased inbreeding in the smaller, more remote subpopulations is especially evident in the increased size and number of runs of homozygosity. The Florida scrub-jay displays limited dispersal, and habitat fragmentation has greatly reduced the magnitude of gene flow in the past 30 years, resulting in further decline of genetic diversity, especially in the peripheral populations. Analysis of these data is informative in guiding conservation efforts to retain genetic diversity and minimize the consequences of inbreeding in the Florida scrub-jay. HighlightsO_LIFive regional populations show distinct degrees of population isolation and decline. C_LIO_LIThere has been commensurate loss of genetic diversity, skewed site frequency spectra, reduced migration, and increased inbreeding (FROH). C_LIO_LIAs many state-wide populations decline, the smaller, more remote populations provide a glimpse into the future and a testbed for remediation approaches. C_LI

genomics↗

bioRxiv2024

Longitudinal sequencing reveals polygenic andepistatic nature of genomic response to selection

Evolutionary adaptation to new environments likely results from a combination of selective sweeps and polygenic shifts, depending on the genetic architecture of traits under selection. While selective sweeps have been widely studied, polygenic responses are considered more prevalent but challenging to quantify. The infinitesimal model makes explicit the hypothesis about the dynamics of changes in allele frequencies under selection, where only allelic effect sizes, frequencies, linkage, and gametic disequilibrium matter. Departures from this, like long-range correlations of allele frequency changes, could be a signal of epistasis in polygenic response. We performed an Evolve & Resequence experiment in Drosophila melanogaster exposing flies to a high-sugar diet as a source of environmental stress for over 100 generations. We tracked allele frequency changes in >3000 individually sequenced flies as well as population pools and searched for loci under selection by identifying sites with allele frequency trajectories that differentiated selection regimes consistently across replicates. We estimate that at least 4% of the genome was under positive selection, the result of a highly polygenic response. Most of this response was seen as small but consistent allele frequency changes over time, and there were only a few large allele-frequency changes (selective sweeps). We then searched for signatures of selection on pairwise combinations of alleles in the new environment and found several strong signals of putative epistatic interactions across unlinked loci that were consistent across selected populations. Finally, we measured differentially expressed genes (DEGs) across treatments and show that DEGs are enriched for selected SNPs, suggesting a regulatory basis for the selective response. Our results suggest that epistatic contributions to polygenic selective response are common and lead to detectable signatures.

evolutionary biology↗

bioRxiv2024

e3SIM: epidemiological-ecological-evolutionary simulation framework for genomic epidemiology

Infectious disease dynamics are driven by the complex interplay of epidemiological, ecological, and evolutionary processes. Accurately modeling these interactions is crucial for understanding pathogen spread and informing public health strategies. However, existing simulators often fail to capture the dynamic interplay between these processes, resulting in oversimplified models that do not fully reflect real-world complexities in which the pathogens genetic evolution dynamically influences disease transmission. We introduce the epidemiological-ecological-evolutionary simulator (e3SIM), an open-source framework that concurrently models the transmission dynamics and molecular evolution of pathogens within a host population while integrating environmental factors. Using an agent-based, discrete-generation, forward-in-time approach, e3SIM incorporates compartmental models, host-population contact networks, and quantitative-trait models for pathogens. This integration allows for realistic simulations of disease spread and pathogen evolution. Key features include a modular and scalable design, flexibility in modeling various epidemiological and population-genetic complexities, incorporation of time-varying environmental factors, and a user-friendly graphical interface. We demonstrate e3SIMs capabilities through simulations of realistic outbreak scenarios with SARS-CoV-2 and Mycobacterium tuberculosis, illustrating its flexibility for studying the genomic epidemiology of diverse pathogen types.

bioinformatics↗