arXiv subjects

Oskar Hallatschek

Publications and source records attributed to Oskar Hallatschek.

33 records · Page 2Linked to original sources

arXiv2012

Supplementary information for "Selective sweeps in growing microbial colonies"

This is supplementary information for arXiv:1204.4896, which also appeared in Physical Biology 9, 026008 (2012). Main text abstract: Evolutionary experiments with microbes are a powerful tool to study mutations and natural selection. These experiments, however, are often limited to the well-mixed environments of a test tube or a chemostat. Since spatial organization can significantly affect evolutionary dynamics, the need is growing for evolutionary experiments in spatially structured environments. The surface of a Petri dish provides such an environment, but a more detailed understanding of microbial growth on Petri dishes is necessary to interpret such experiments. We formulate a simple deterministic reaction-diffusion model, which successfully predicts the spatial patterns created by two competing species during colony expansion. We also derive the shape of these patterns analytically without relying on microscopic details of the model. In particular, we find that the relative fitness of two microbial strains can be estimated from the logarithmic spirals created by selective sweeps. The theory is tested with strains of the budding yeast Saccharomyces cerevisiae, for spatial competitions with different initial conditions and for a range of relative fitnesses. The reaction-diffusion model also connects the microscopic parameters like growth rates and diffusion constants with macroscopic spatial patterns and predicts the relationship between fitness in liquid cultures and on Petri dishes, which we confirmed experimentally. Spatial sector patterns therefore provide an alternative fitness assay to the commonly used liquid culture fitness assays.

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arXiv2012

The rate of beneficial mutations surfing on the wave of a range expansion

Many theoretical and experimental studies suggest that range expansions can have severe consequences for the gene pool of the expanding population. Due to strongly enhanced genetic drift at the advancing frontier, neutral and weakly deleterious mutations can reach large frequencies in the newly colonized regions, as if they were surfing the front of the range expansion. These findings raise the question of how frequently beneficial mutations successfully surf at shifting range margins, thereby promoting adaptation towards a range-expansion phenotype. Here, we use individual-based simulations to study the surfing statistics of recurrent beneficial mutations on wave-like range expansions in linear habitats. We show that the rate of surfing depends on two strongly antagonistic factors, the probability of surfing given the spatial location of a novel mutation and the rate of occurrence of mutations at that location. The surfing probability strongly increases towards the tip of the wave. Novel mutations are unlikely to surf unless they enjoy a spatial head start compared to the bulk of the population. The needed head start is shown to be proportional to the inverse fitness of the mutant type, and only weakly dependent on the carrying capacity. The second factor is the mutation occurrence which strongly decreases towards the tip of the wave. Thus, most successful mutations arise at an intermediate position in the front of the wave. We present an analytic theory for the tradeoff between these factors that allows to predict how frequently substitutions by beneficial mutations occur at invasion fronts. We find that small amounts of genetic drift increase the fixation rate of beneficial mutations at the advancing front, and thus could be important for adaptation during species invasions.

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arXiv2011

Spatial structure increases the waiting time for cancer

Cancer results from a sequence of genetic and epigenetic changes which lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells, and thus, to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has been experiencing increasing interest in recent years. Many efforts have been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured epithelial tissues. We propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to asses two different paradigms of asexual evolution that have been suggested to delineate the process of cancer progression. The standard scenario of periodic selection assumes that driver mutations are accumulated strictly sequentially over time. However, when the mutation supply is sufficiently high, clones may arise simultaneously on distinct genetic backgrounds, and clonal adaptation waves interfere with each other. We find that in the presence of clonal interference, spatial structure increases the waiting time for cancer, leads to a patchwork structure of non-uniformly sized clones, decreases the survival probability of virtually neutral (passenger) mutations, and that genetic distance begins to increase over a characteristic length scale, determined here. These characteristic features of clonal interference may help to predict the onset of cancers with pronounced spatial structure and to interpret spatially-sampled genetic data obtained from biopsies. Our estimates suggest that clonal interference likely occurs in the progressing colon cancer, and possibly other cancers where spatial structure matters.

q-bio.PE↗

arXiv2011

The noisy edge of traveling waves

Traveling waves are ubiquitous in nature and control the speed of many important dynamical processes, including chemical reactions, epidemic outbreaks, and biological evolution. Despite their fundamental role in complex systems, traveling waves remain elusive because they are often dominated by rare fluctuations in the wave tip, which have defied any rigorous analysis so far. Here, we show that by adjusting nonlinear model details, noisy traveling waves can be solved exactly. The moment equations of these tuned models are closed and have a simple analytical structure resembling the deterministic approximation supplemented by a nonlocal cutoff term. The peculiar form of the cutoff shapes the noisy edge of traveling waves and is critical for the correct prediction of the wave speed and its fluctuations. Our approach is illustrated and benchmarked using the example of fitness waves arising in simple models of microbial evolution, which are highly sensitive to number fluctuations. We demonstrate explicitly how these models can be tuned to account for finite population sizes and determine how quickly populations adapt as a function of population size and mutation rates. More generally, our method is shown to apply to a broad class of models, in which number fluctuations are generated by branching processes. Because of this versatility, the method of model tuning may serve as a promising route toward unraveling universal properties of complex discrete particle systems.

q-bio.PE↗

arXiv2011

Genetic Demixing and Evolutionary Forces in the One-Dimensional Stepping Stone Model

We review and extend results for mutation, selection, genetic drift, and migration in a one-dimensional continuous population. The population is described by a continuous limit of the stepping stone model, which leads to the stochastic Fisher-Kolmogorov-Petrovsky-Piscounov equation with additional terms describing mutations. Although the stepping stone model was first proposed for population genetics, it is closely related to "voter models" of interest in nonequilibrium statistical mechanics. The stepping stone model can also be regarded as an approximation to the dynamics of a thin layer of actively growing pioneers at the frontier of a colony of microorganisms undergoing a range expansion on a Petri dish. We find that the population tends to segregate into monoallelic domains. This segregation slows down genetic drift and selection because these two evolutionary forces can only act at the boundaries between the domains; the effects of mutation, however, are not significantly affected by the segregation. Although fixation in the neutral well-mixed (or "zero dimensional") model occurs exponentially in time, it occurs only algebraically fast in the one-dimensional model. If selection is weak, selective sweeps occur exponentially fast in both well-mixed and one-dimensional populations, but the time constants are different. We also find an unusual sublinear increase in the variance of the spatially averaged allele frequency with time. Although we focus on two alleles or variants, q-allele Potts-like models of gene segregation are considered as well. We also investigate the effects of geometry at the frontier by considering growth of circular colonies. Our analytical results are checked with simulations, and could be tested against recent spatial experiments on range expansions off linear inoculations of Escherichia coli and Saccharomyces cerevisiae.

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arXiv2009

Fisher waves in the strong noise limit

We investigate the effects of strong number fluctuations on traveling waves in the Fisher-Kolmogorov reaction-diffusion system. Our findings are in stark contrast to the commonly used deterministic and weak-noise approximations. We compute the wave velocity in one and two spatial dimensions, for which we find a linear and a square-root dependence of the speed on the particle density. Instead of smooth sigmoidal wave profiles, we observe fronts composed of a few rugged kinks that diffuse, annihilate, and rarely branch; this dynamics leads to power-law tails in the distribution of the front sizes.

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arXiv2008

Life at the front of an expanding population

Recent microbial experiments suggest that enhanced genetic drift at the frontier of a two-dimensional range expansion can cause genetic sectoring patterns with fractal domain boundaries. Here, we propose and analyze a simple model of asexual biological evolution at expanding frontiers to explain these neutral patterns and predict the effect of natural selection. Our model attributes the observed gradual decrease in the number of sectors at the leading edge to an unbiased random walk of sector boundaries. Natural selection introduces a deterministic bias in the wandering of domain boundaries that renders beneficial mutations more likely to escape genetic drift and become established in a sector. We find that the opening angle of those sectors and the rate at which they become established depend sensitively on the selective advantage of the mutants. Deleterious mutations, on the other hand, are not able to establish a sector permanently. They can, however, temporarily "surf" on the population front, and thereby reach unusual high frequencies. As a consequence, expanding frontiers are susceptible to deleterious mutations as revealed by the high fraction of mutants at mutation-selection balance. Numerically, we also determine the condition at which the wild type is lost in favor of deleterious mutants (genetic meltdown) at a growing front. Our prediction for this error threshold differs qualitatively from existing well-mixed theories, and sets tight constraints on sustainable mutation rates for populations that undergo frequent range expansions.

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arXiv2008

Genetic drift at expanding frontiers promotes gene segregation

Competition between random genetic drift and natural selection plays a central role in evolution: Whereas non-beneficial mutations often prevail in small populations by chance, mutations that sweep through large populations typically confer a selective advantage. Here, however, we observe chance effects during range expansions that dramatically alter the gene pool even in large microbial populations. Initially well-mixed populations of two fluorescently labeled strains of Escherichia coli develop well-defined, sector-like regions with fractal boundaries in expanding colonies. The formation of these regions is driven by random fluctuations that originate in a thin band of pioneers at the expanding frontier. A comparison of bacterial and yeast colonies (Saccharomyces cerevisiae) suggests that this large-scale genetic sectoring is a generic phenomenon that may provide a detectable footprint of past range expansions.

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arXiv2007

Coupling of transverse and longitudinal response in stiff polymers

The time-dependent transverse response of stiff polymers, represented as weakly-bending wormlike chains (WLCs), is well-understood on the linear level, where transverse degrees of freedom evolve independently from the longitudinal ones. We show that, beyond a characteristic time scale, the nonlinear coupling of transverse and longitudinal motion in an inextensible WLC significantly weakens the polymer response compared to the widely used linear response predictions. The corresponding feedback mechanism is rationalized by scaling arguments and quantified by a multiple scale approach that exploits an inherent separation of transverse and longitudinal correlation length scales. Crossover scaling laws and exact analytical and numerical solutions for characteristic response quantities are derived for different experimentally relevant setups. Our findings are applicable to cytoskeletal filaments as well as DNA under tension.

cond-mat.soft↗

arXiv2007

Gene surfing

Spatially resolved genetic data is increasingly used to reconstruct the migrational history of species. To assist such inference, we study, by means of simulations and analytical methods, the dynamics of neutral gene frequencies in a population undergoing a continual range expansion in one dimension. During such a colonization period, lineages can fix at the wave front by means of a ``surfing'' mechanism [Edmonds C.A., Lillie A.S. & Cavalli-Sforza L.L. (2004) Proc Natl Acad Sci USA 101: 975-979]. We quantify this phenomenon in terms of (i) the spatial distribution of lineages that reach fixation and, closely related, (ii) the continual loss of genetic diversity (heterozygosity) at the wave front, characterizing the approach to fixation. Our simulations show that an effective population size can be assigned to the wave that controls the (observable) gradient in heterozygosity left behind the colonization process. This effective population size is markedly higher in pushed waves than in pulled waves, and increases only sub-linearly with deme size. To explain these and other findings, we develop a versatile analytical approach, based on the physics of reaction-diffusion systems, that yields simple predictions for any deterministic population dynamics.

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arXiv2006

Dynamics of Semiflexible Polymers in a Flow Field

We present a novel method to investigate the dynamics of a single semiflexible polymer, subject to anisotropic friction in a viscous fluid. In contrast to previous approaches, we do not rely on a discrete bead-rod model, but introduce a suitable normal mode decomposition of a continuous space curve. By means of a perturbation expansion for stiff filaments we derive a closed set of coupled Langevin equations in mode space for the nonlinear dynamics in two dimensions, taking into account exactly the local constraint of inextensibility. The stochastic differential equations obtained this way are solved numerically, with parameters adjusted to describe the motion of actin filaments. As an example, we show results for the tumbling motion in shear flow.

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arXiv2006

Tension dynamics in semiflexible polymers. Part I: Coarse-grained equations of motion

Based on the wormlike chain model, a coarse-grained description of the nonlinear dynamics of a weakly bending semiflexible polymer is developed. By means of a multiple scale perturbation analysis, a length-scale separation inherent to the weakly-bending limit is exploited to reveal the deterministic nature of the spatio-temporal relaxation of the backbone tension and to deduce the corresponding coarse-grained equation of motion. From this partial integro-differential equation, some detailed analytical predictions for the non-linear response of a weakly bending polymer are derived in an accompanying paper (Part II, cond-mat/0609638).

cond-mat.soft↗

arXiv2006

Tension dynamics in semiflexible polymers. Part II: Scaling solutions and applications

In Part I of this contribution, a systematic coarse-grained description of the dynamics of a weakly-bending semiflexible polymer was developed. Here, we discuss analytical solutions of the established deterministic partial integro-differential equation for the spatio-temporal relaxation of the backbone tension. For prototypal experimental situations, such as the sudden application or release of a strong external pulling force, it is demonstrated that the tensile dynamics reflects the self-affine conformational fluctuation spectrum in a variety of intermediate asymptotic power laws. Detailed and explicit analytical predictions for the tension propagation and relaxation and corresponding results for common observables, such as the end-to-end distance, are obtained.

cond-mat.soft↗

arXiv2005

Propagation and Relaxation of Tension in Stiff Polymers

We present a unified theory for the longitudinal dynamic response of a stiff polymer in solution to various external perturbations (mechanical excitations, hydrodynamic flows, electrical fields, temperature quenches ...) that can be represented as sudden changes of ambient/boundary conditions. The theory relies on a comprehensive analysis of the non--equilibrium propagation and relaxation of backbone stresses in a wormlike chain. We recover and substantially extend previous results based on heuristic arguments. Intriguing new experimental implications are pointed out.

cond-mat.soft↗

arXiv2004

Overdamped Stress Relaxation in Buckled Rods

We present a comprehensive theoretical analysis of the stress relaxation in a multiply but weakly buckled incompressible rod in a viscous solvent. In the bulk two interesting regimes of generic self--similar intermediate asymptotics are distinguished, which give rise to two classes of approximate and exact power--law solutions, respectively. For the case of open boundary conditions the corresponding non--trivial boundary--layer scenarios are derived by a multiple--scale perturbation (``adiabatic'') method. Our results compare well with -- and provide the theoretical explanation for -- previous results from numerical simulations, and they suggest new directions for further fruitful numerical and experimental investigations.

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