Biology subjects

Sneppen, K.

Publications and source records attributed to Sneppen, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Survivorship Bias Explains Age-Dependent Extinction in Fossil Genera

Fossil genera exhibit pronounced age-dependent extinction: older genera are more likely to survive extinction events than younger ones. Many biological mechanisms have been proposed that could make lineages progressively more resistant to extinction through time. However, the same pattern can also arise from survivorship bias: as more vulnerable genera are progressively eliminated, the surviving pool becomes increasingly enriched in robust lineages, even if the properties of individual lineages never change. Using the Sepkoski marine genus compendium, we construct a quantitative model based solely on survivorship bias and ask whether additional age-dependent changes are required to explain the fossil record. This model with a single fitting parameter quantitatively reproduces the full set of age-conditioned survival probabilities, together with the overall dependence of extinction risk on genus age and the genus lifetime distribution. Allowing extinction resistance to change systematically through time yields no measurable improvement, indicating that, at least at the aggregate statistical level, explicit age-dependent changes in lineage properties are not required to explain the observed patterns of extinction. These results show that our minimal one-parameter model provides a quantitative null model for age-dependent extinction, against which proposed biological mechanisms can now be tested.

paleontology↗

bioRxiv2026

Multivalent Surface Search Dynamics Shape Bacteriophage Adsorption Efficiency: A Stochastic Model of Tail Fiber Optimization

Phages must locate and bind to bacterial surface receptors to initiate infection. Their tail fiber configuration critically influences this process. We develop a stochastic model describing surface search as a renewal process, incorporating attachment, detachment, and target-finding steps. Using both numerical simulations and analytical calculations, we quantify how tail fiber number, attachment-detachment rates, and geometric constraints impact the mean and the distribution of time to successful adsorption. Notably, the search efficiency shows a nonmonotonic dependence on tail fibers number, governed by a trade-off between binding stability and diffusion-mediated mobility. This optimum shifts depending on the effective bacterial density, target radius, and fiber reach. Short fiber reach imposes severe geometric constraints, reducing mobility at high tail fiber counts and leading to performance degradation. Our findings suggest that phage adsorption strategies are shaped by a balance between anchoring and exploration, with evolutionary implications for tail fiber design and infection efficiency. SIGNIFICANCEBacteriophages typically use tail fibers to bind and explore bacterial surfaces. Using stochastic modeling and numerical simulations, we uncover how attachment-detachment kinetics and tail fiber geometry shape surface search efficiency. Our results reveal a trade-off: more tail fibers stabilize attachment but hinder exploration, especially with short reattachment ranges. These findings offer a mechanistic basis for understanding how phages optimize infection strategies and may explain the diversity of tail architectures observed in nature.

biophysics↗

bioRxiv2026

Stochasticity in viral infection and host response: A competition between speed and reliability

The early stages of viral infection constitute a race between viral proliferation and interferon (IFN)-mediated defenses. Recent experiments on single-cell viral kinetics have demonstrated a high degree of stochasticity in the timing of viral release, but how this shapes the competition between virus and host remains unclear. We formulate a stochastic spatial model to address the question of how variability in the release of viral progeny and IFN affect the early infection dynamics. The model distinguishes between two types of timing noise: stochasticity in the initiation of release, and variability in the secretion time of individual virions. Our key result is an asymmetry in how noise affects outcomes: For the virus, stochastic initiation accelerates expansion, while for the host, effective containment via IFN benefits from precisely timed responses. For the secreting states, we find that a broader secretion profile (higher variability in particle release times) is always advantageous. In all cases, we find that stochasticity in signal timing plays a huge/central role in the early infections states.

immunology↗

bioRxiv2025

Modeling assembly dynamics and stability of microbial communities

Predicting the species composition of microbial communities is a problem that has proven surprisingly difficult, including in fully controlled microbial systems in a lab setting. Few organisms are able to establish themselves in an community with no others, even if nutrients are provided. At the same time some species are observed to be unable to stably coexist with certain other species. We here present a model attempting to reduce the dynamics of community assembly to its most basic components, while preserving its salient features. The model deals not with abundances or densities of bacterial populations or resources, but only with their presence or absence. Similarly, only three types of discrete relationships between species are considered: species excluding each other, and mutualistic dependence on and production of nutrients in the form of exometabolites. Despite these simplifications, the model system still exhibits rich dynamics, including extinction cascades and emerging stability against invasion. We derive conditions for these to occur and compare our results with existing knowledge of microbial communities. Our results provide a novel approach for the theoretical study of microbial communities and their stability. SignificanceUnderstanding the processes governing the community composition of microbial ecosystems is an as-yet unsolved problem. In this article, we propose a novel rule-based model for the assembly and stability of communities of microbial species. Despite its simplicity the model exhibits rich dynamics, including critical points and extinction cascades. It presupposes no knowledge of specific population parameters or exact resource or species abundances, but focuses on pairwise interactions between species and their metabolites. The framework may be useful for understanding how real microbial communities arise and what causes them to break down.

ecology↗

bioRxiv2025

Viral Infection Depends on Host's Metabolism

Viral infection begins with attachment to host surface structures such as receptors, pili, or porins. While prior research has focused on structural compatibility and recognition, the role of host physiology, particularly metabolic state, on viral commitment to infection remains underexplored. Here, we measured the adsorption rates () of five Escherichia coli phages representing various life cycles and entry pathways under controlled metabolic conditions. Four phages showed significantly reduced adsorption under energy-limited states, with weaker-binding phages being more sensitive. Using E. coli and its phages allowed us to institute a number of control infections that would be difficult with other organisms. Our findings support a two-step infection model where bound phages may disengage under unfavorable conditions, reducing commitment to non-productive infections. We observed a correlation between adsorption rates under energy-competent conditions and sensitivity to host metabolic state. Our results highlight host physiology as a key factor in virus-host interactions under energy-limited conditions.

microbiology↗

bioRxiv2025

When Not to Kill Your Host in Competitive Bust-Boom Environments

Temperate phages, which can either kill their host cells or integrate into them, struggle to compete with purely virulent phages in environments with plenty of available hosts. This suggests that their survival strategy is fine-tuned for unstable conditions, where they hedge their bets between immediate replication and long-term persistence as an integrated prophage. In this study, we explored how temperate phages make these life-or-death decisions, both in isolation and when competing with other phages. We found that when temperate phages compete with each other, those with relatively stable lysogens survive better. Environments with competitive temperate phages further select for lower lysogeny frequency. Our findings suggest that dosage-dependent lysogeny choice is adapted to competing phages with overlapping immunity. In environments where phages can disperse between separate sub-systems that fluctuate independently, temperate phages struggle to survive against virulent phages.

microbiology↗

bioRxiv2024

Self-organized coexistence of phage and a population of host colonies

Phages and bacteria coexist under widely different conditions, ranging from liquid cultures to oceans, soil, and the human gut. However, our models are typically limited to well-mixed liquid cultures governed by mass-action kinetics. Here, we suggest a modification to the Lotka-Volterra dynamics by including the formation of microcolonies. By analyzing the model in an open system with a steady influx of bacteria, we predict that the colony size distribution is power-low distributed with steeper exponents for the stronger external influx. In the realistic case where the phage attack rate to individual colonies is proportional to their radius, we obtain self-organization to a steady state where the maximal colony size is smaller for stronger external driving.

ecology↗

bioRxiv2023

The dynamics of phage predation on a microcolony

Phage predation is an important factor for controlling the bacterial biomass. At face value, dense microbial habitats are expected to be vulnerable to phage epidemics due to the abundance of fresh hosts immediately next to any infected bacteria. Despite this, the bacterial microcolony is a common habitat for bacteria in nature. Here we experimentally quantify the fate of microcolonies of Escherichia coli exposed to virulent phage T4. It has been proposed that the outer bacterial layers of the colony will shield the inner layers from the phage invasion and thereby constrain the phage to the colonys surface. We develop a dynamical model that incorporates this shielding mechanism and fits the results with experimental measurements to extract important phage-bacteria interaction parameters. The analysis suggests that, while the shielding mechanism delays phage attack,T4 phage are able to diffuse so deep into the dense bacterial environment that colony level survival of the bacterial community is challenged. SignificanceThe shielding mechanism of bacterial microcolonies against phage invasion has been experimentally quantified, and the result was analyzed by using a mathematical model. The analysis suggests that while forming a dense colony delays phage attack by limiting the infection closer to the colony surface,T4 phage can diffuse so deep into the dense bacterial environment that colony-level survival of the bacterial community is challenged. This finding highlights the importance of the interplay between the phage infection dynamics and the physical structure of bacterial colonies in controlling the microbial population.

microbiology↗

bioRxiv2021

Emergence of networks of shared restriction-modification systems in phage-bacteria ecosystems

1Restriction-modification (RM) systems are the most ubiquitous bacterial defense system against bacteriophages and an important part of controlling phage predation. Using genomic sequence data, we show that RM systems are often shared among bacterial strains in a structured way. Examining the network of interconnections between bacterial strains within each genus, we find that in many genera strains share more RM systems than expected from a random network. We also find that many genera have a larger than expected number of bacterial strains with unique RM systems. We use population dynamics models of closed and open phage-bacteria ecosystems to qualitatively understand the selection pressures that could lead to these non-random network structures with enhanced overlap or uniqueness. In our models we find that the phages impose a pressure that favours bacteria with more RM systems, and more overlap of RM systems with other strains, but in bacteria dominated states this is opposed by the increased cost to the growth rate of these bacteria. Similar to what we observe in the genome data, we find that two distinct bacterial strategies emerge - strains either have a larger overlap than expected, or they have more unique RM systems than one expects from a null model. The former strategy appears to dominate when the repertoire of available RM systems is smaller but the average number of RM systems per strain is larger.

microbiology↗

bioRxiv2021

The timing of natural killer cell response in coronavirus infection: a concise model perspective

Coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2 cause respiratory diseases with remarkably heterogeneous progression. This in part reflects the viral ability to influence the cytokine secretion and thereby the innate immune system. Especially the viral interference of IFN-I signaling and the subsequent deficiency of innate immune response in the early phase have been associated with rapid virus replication and later excessive immune responses. We propose a mathematical framework to analyze IFN-I signaling and its impact on the interaction motif between virus, NK cells and macrophages. The model recapture divergent dynamics of coronavirus infections including the possibility for elevated secretion of IL-6 and IFN-{gamma} as a consequence of exacerbated macrophage activation. Dysfunction of NK cells recruitment increase disease severity by leading to a higher viral load peak, the possibility for excessive macrophage activation, and an elevated risk of the cytokine storm. Thus the model predicts that delayed IFN-I signaling could lead to pathogenicity in the latter stage of an infection. Reversely, in case of strong NK recruitment from infected cells we predict a possible chronic disease state with moderate and potentially oscillating virus/cytokine levels.

biophysics↗

bioRxiv2020

ICM cells can be partitioned robustly throughtransient synchronization using secreted FGF4

The differentiation of ICM cells into epiblast (EPI) and primitive endoderm (PE) is central in embryonic development. It is known that FGF4 signaling is important in this process, but it remains unclear how cells can be correctly partitioned. Here we model the NANOG-GATA6-FGF4 network, and test all 64 logical regulatory combinations for their ability to partition a group of cells. We found that nearly all the logic combinations allowed for correct partitioning, including a minimal network where self-activation of NANOG and GATA6 was inactivated. However such self-activation increased the robustness of the system. Furthermore, the model also captured the reported changes in cell proportions in response to FGF perturbations. This constrains the possible regulatory logic and predicts the presence of an "OR" gate in cell-cell communication. We repeatedly found that FGF4 coordinated the decision in two phases: A convergence and a bifurcation phase. First FGF4 negative feedback drives the cells to a balanced "battle" state where most cells have intermediate levels of both regulators, thus being double positive. Subsequent bifurcation happens at constant FGF4 level. Together our results suggest that the frequently observed state of multipotency during differentiation may be an emergent phenomenon resulting from inter-cellular negative feedbacks.

developmental biology↗

bioRxiv2020

On phage adsorption to bacterial chains

Bacteria often arrange themselves in various spatial configurations which changes how they interact with their surroundings. In this paper, we investigate in silico how the structure of the bacterial arrangements influences the adsorption of bacteriophages. We quantify how the adsorption rate scales with the number of bacteria in the arrangement, and show that the adsorption rates for microcolonies (increasing with exponent [~]1/3) and bacterial chains (increasing with exponent [~]0.5 - 0.8) are substantially lower than for well-mixed bacteria (increasing with exponent 1). We further show that, after infection, the spatially clustered arrangements reduce the effective burst size by more than 50 % and cause substantial superinfections in a very short time interval after phage lysis. SIGNIFICANCEWhen bacteria forms clusters they substantially change their exposure to invading phages and other external agents from the well-mixed scenario. Despite this fact, much research has focused on and is focusing on using well-mixed bacteria. Understanding the kinetics of the spatial structures is paramount to developing robust analyses and theories of experimental results. We carefully investigate how the clusters lower the adsorption rate of external phages and how the clustering modifies the hit probabilities for the bacteria.

biophysics↗

bioRxiv2019

Disease as an evolutionary weapon

Disease and predation are both highly important in ecology, and pathogens with multiple host species have turned out to be common. Nonetheless, the interplay between multi-host epidemics and predation has received relatively little attention. Here, we analyse a model of a predator-prey system with disease in both prey and predator populations and determine reasonable parameter values using allometric mass scaling relations. Our analysis focuses on the possibility of extinction events rather than the linear stability of the model equations. We find that if the predator is a specialist, epidemics frequently drive the predator species to extinction. If the predator has an additional, immune prey species, predators will usually survive. Coexistence of predator and disease is impossible in the single-prey model. We conclude that for the prey species, carrying a pathogen can be an effective weapon against predators, and that being a generalist is a major advantage for a predator.

ecology↗

bioRxiv2019

Model to link cell shape and polarity with organogenesis

How do tubes -- gut or neural tube -- form from flat sheets of polarized cells? The prevalent view is that it is a two-step process: first cells wedge to bend the sheet, then cells intercalate and extend the initial invagination into a tube. We computationally challenged this model by asking if one mechanism (either cell wedging or intercalation) may suffice for the entire sheet-to-tube transition. Using a physical model with epithelial cells represented by polarized point particles, we show that either cell intercalation or wedging alone can be sufficient and each can both bend the sheet and extend the tube. When working in parallel, the two mechanisms increase the robustness of the tube formation. The successful simulations of Drosophila salivary gland, Sea urchin gastrulation and mammalian neurulation support the generality of our results.

developmental biology↗

bioRxiv2018

Sustainability of spatially distributed bacteria-phage systems

Virulent phages can expose their bacterial hosts to devastating epidemics, in principle opening for a complete elimination of their hosts. Although experiments indeed confirm large reduction of susceptible bacteria, there is no reports of complete extinctions. We here address this phenomenon from the perspective of spatial organization of bacteria and how this can influence the final survival of them. By modeling the transient dynamics of bacteria and phages when they are introduced into an environment with finite resources, we quantify how the spatial separation of initial bacterial positions and the self-protection of bacteria growing in spherical colonies favor bacterial survival. This suggest that spatial structures on the millimeter scale plays an important role in maintaining microbial diversity.

ecology↗

bioRxiv2018

Hitchhiking, collapse and contingency in phage infections of migrating bacterial populations

Natural bacterial populations are subject to constant predation pressure by phages. Bacteria use a variety of well-studied molecular mechanisms to defend themselves from phage predation. However, since phage are non-motile, perhaps the simplest defense against phage would be for bacteria to outrun their predators. In particular, chemotaxis, the active migration of bacteria up attractant gradients, may help the bacteria escape slowly diffusing phages. Here we study phage infection dynamics in migrating bacterial populations driven by chemotaxis through low viscosity agar plates. We find that expanding phage-bacteria populations support two migrating fronts, an outermost \"bacterial\" front driven by nutrient uptake and chemotaxis and an inner \"phage\" front at which bacterial population collapses due to phage predation. We show that with increasing adsorption rate and initial phage population, the rate of migration of the phage front increases, eventually overtaking the bacterial front and driving the system across a \"phage transition\" from a regime where bacteria outrun a phage infection to one where they must evolve phage resistance to survive. We confirm experimentally that this process requires phages to \"surf\" the bacterial front by repeatedly reinfecting the fastest moving bacteria. A deterministic model recapitulates the transition. Macroscopic fluctuations in bacterial densities at the phage front suggest that a feedback mechanism, possibly due to growth rate dependent phage infection rates, drives millimeter scale spatial structure in phage-bacteria populations. Our work opens a new, spatiotemporal, line of investigation into the eco-evolutionary struggle between bacteria and their phage predators.\n\nSignificance StatementThe infection of bacteria by phage requires physical contact. This fact means that motile bacteria may avoid non-motile phage by simply running away. By this mechanism bacterial chemotaxis may help bacteria to escape phages. Here we show that when phage infect bacteria moving in soft agar plates, high phage populations or infectivity rates result in phages stopping and killing all bacteria. Conversely, when initial phage numbers or infectivity rates are low, bacteria are able to migrate away from phage successfully, despite phage ability to \"surf\" bacterial fronts for more than 24 hours. Between these regimes we document a \"phage transition\" where bacterial physiology and contingency in phage infection manifest through large-scale fluctuations in spatio-temporal dynamics.

ecology↗

bioRxiv2018

Theory bridging cell polarities with development of robust complex morphologies

Despite continual renewal and damages, a multicellular organism is able to maintain its complex morphology. How is this stability compatible with the complexity and diversity of living forms? Looking for answers at protein level may be limiting as diverging protein sequences can result in similar morphologies. Inspired by the progressive role of apical-basal and planar cell polarity in development, we propose that stability, complexity, and diversity are emergent properties in populations of proliferating polarized cells. We support our hypothesis by a theoretical approach, developed to effectively capture both types of polar cell adhesions. When applied to specific cases of development gastrulation and the origins of folds and tubes our theoretical tool suggests experimentally testable predictions pointing to the strength of polar adhesion, restricted directions of cell polarities, and the rate of cell proliferation to be major determinants of morphological diversity and stability.

biophysics↗

bioRxiv2017

A Growing Microcolony can Survive and Support Persistent Propagation of Virulent Phages

Bacteria form colonies and secrete extracellular polymeric substances that surround the individual cells. These spatial structures are often associated with collaboration and quorum sensing between the bacteria. Here we investigate the mutual protection provided by spherical growth of a monoclonal colony during exposure to phages that proliferate on its surface. As a proof of concept we exposed growing colonies of Escherichia coli to a virulent mutant of phage P1. When the colony consists of less than ~ 50000 members it is eliminated, while larger initial colonies allow long-term survival because the growth of bacteria throughout the spherical colony exceeds the killing of bacteria on the surface. A mathematical model pinpoints how this critical colony size depends on key parameters in the phage infection cycle. Surprisingly, we predict that a higher phage adsorption rate would allow substantially smaller colonies to survive a virulent phage.\n\nSignificance StatementBacteria are repeatedly exposed to an excess of phages, and carry evidence of this in terms of multiple defense mechanisms encoded in their genome. In addition to molecular mechanisms, bacteria may exploit the defense of spatial refuges. Here we demonstrate how bacteria can limit the impact of a virulent phage attack by growing as a colony which only exposes its surface to phages. We identify a critical size of the initial colony, below which the phages entirely eliminates the colony, and above which the colony continues to grow despite the presence of phages. Our study suggests that coexistence of phages and bacteria is strongly influenced by the spatial composition of microcolonies of susceptible bacteria.

microbiology↗