SearcharxivSearch

arXiv subjects

Vincent Calvez

Publications and source records attributed to Vincent Calvez.

At least 19 recordsLinked to original sources

Stochastic dynamics at the back of a gene drive eradication wave

Gene drive alleles bias their own inheritance to offspring. They can fix in a wild-type population in spite of a fitness cost, and even lead to the eradication of the target population if the fitness cost is high. However, this outcome may be prevented or delayed if areas previously cleared by the drive are recolonised by wild-type individuals. Here, we investigate the conditions under which these stochastic wild-type recolonisation events are likely and when they are unlikely to occur in one spatial dimension. More precisely, we examine the conditions ensuring that the last individual carrying a wild-type allele is surrounded by a large enough number of drive homozygous individuals, resulting in a very low chance of wild-type recolonisation. To do so, we make a deterministic approximation of the distribution of drive alleles within the wave, and we split the distribution of wild-type alleles into a deterministic part and a stochastic part. Our analytical and numerical results suggest that the probability of wild-type recolonisation events increases with lower fitness of drive individuals and with smaller local carrying capacity. Numerical simulations show that these results extend to two spatial dimensions. The role of the migration rate however, is less clear but has a lower impact. We further demonstrate that, in the event of wild-type recolonization, the probability of subsequent drive reinvasion decreases with smaller values of the intrinsic growth rate of the population. Overall, our study paves the way for further analysis of wild-type recolonisation at the back of eradication traveling waves.

q-bio.PE

Stability analysis for a kinetic bacterial chemotaxis model

We perform stability analysis of a kinetic bacterial chemotaxis model of bacterial self-organization, assuming that bacteria respond sharply to chemical signals. The resulting discontinuous tumbling kernel represents the key challenge for the stability analysis as it rules out a direct linearization of the nonlinear terms. To address this challenge we fruitfully separate the evolution of the shape of the cellular profile from its global motion. We provide a full nonlinear stability theorem in a perturbative setting when chemical degradation can be neglected. With chemical degradation we prove stability of the linearized operator. In both cases we obtain exponential relaxation to equilibrium with an explicit rate using hypocoercivity techniques. To apply a hypocoercivity approach in this setting, we develop two novel and specific approaches: i) the use of the $H^1$ norm instead of the $L^2$ norm, and ii) the treatment of nonlinear terms. This work represents an important step forward in bacterial chemotaxis modeling from a kinetic perspective as most results are currently only available for the macroscopic descriptions, which are usually parabolic in nature. Significant difficulty arises due to the lack of regularization of the kinetic transport operator as compared to the parabolic operator in the macroscopic scaling limit.

math.AP

Uniform contractivity of the Fisher infinitesimal model with strongly convex selection

The Fisher infinitesimal model is a classical model of phenotypic trait inheritance in quantitative genetics. Here, we prove that it encompasses a remarkable convexity structure which is compatible with a selection function having a convex shape. It yields uniform contractivity along the flow, as measured by a $L^\infty$ version of the Fisher information. It induces in turn asynchronous exponential growth of solutions, associated with a well-defined, log-concave, equilibrium distribution. Although the equation is non-linear and non-conservative, our result shares some similarities with the Bakry-Emery approach to the exponential convergence of solutions to the Fokker-Planck equation with a convex potential. Indeed, the contraction takes place at the level of the Fisher information. Moreover, the key lemma for proving contraction involves the Wasserstein distance $W_\infty$ between two probability distributions of a (dual) backward-in-time process, and it is inspired by a maximum principle by Caffarelli for the Monge-Amp\`ere equation.

math.PR

Pulled, pushed or failed: the demographic impact of a gene drive can change the nature of its spatial spread

Understanding the temporal spread of gene drive alleles -- alleles that bias their own transmission -- through modeling is essential before any field experiments. In this paper, we present a deterministic reaction-diffusion model describing the interplay between demographic and allelic dynamics, in a one-dimensional spatial context. We focused on the traveling wave solutions, and more specifically, on the speed of gene drive invasion (if successful). We considered various timings of gene conversion (in the zygote or in the germline) and different probabilities of gene conversion (instead of assuming 100$\%$ conversion as done in a previous work). We compared the types of propagation when the intrinsic growth rate of the population takes extreme values, either very large or very low. When it is infinitely large, the wave can be either successful or not, and, if successful, it can be either pulled or pushed, in agreement with previous studies (extended here to the case of partial conversion). In contrast, it cannot be pushed when the intrinsic growth rate is vanishing. In this case, analytical results are obtained through an insightful connection with an epidemiological SI model. We conducted extensive numerical simulations to bridge the gap between the two regimes of large and low growth rate. We conjecture that, if it is pulled in the two extreme regimes, then the wave is always pulled, and the wave speed is independent of the growth rate. This occurs for instance when the fitness cost is small enough, or when there is stable coexistence of the drive and the wild-type in the population after successful drive invasion. Our model helps delineate the conditions under which demographic dynamics can affect the spread of a gene drive.

math.AP

Concentration in Lotka-Volterra parabolic equations: an asymptotic-preserving scheme

In this paper, we introduce and analyze an asymptotic-preserving scheme for Lotka-Volterra parabolic equations. It is a class of nonlinear and nonlocal stiff equations, which describes the evolution of a population structured with phenotypic trait. In a regime of long time and small mutations, the population concentrates at a set of dominant traits. The dynamics of this concentration is described by a constrained Hamilton-Jacobi equation, which is a system coupling a Hamilton-Jacobi equation with a Lagrange multiplier determined by a constraint. This coupling makes the equation nonlocal. Moreover, the constraint does not enjoy much regularity, since it can have jumps. The scheme we propose is convergent in all the regimes, and enjoys stability in the long time and small mutations limit. Moreover, we prove that the limiting scheme converges towards the viscosity solution of the constrained Hamilton-Jacobi equation, despite the lack of regularity of the constraint. The theoretical analysis of the schemes is illustrated and complemented with numerical simulations.

math.AP

The best of both worlds: Combining population genetic and quantitative genetic models

Numerous traits under migration-selection balance are shown to exhibit complex patterns of genetic architecture with large variance in effect sizes. However, the conditions under which such genetic architectures are stable have yet to be investigated, because studying the influence of a large number of small allelic effects on the maintenance of spatial polymorphism is mathematically challenging, due to the high complexity of the systems that arise. In particular, in the most simple case of a haploid population in a two-patch environment, while it is known from population genetics that polymorphism at a single major-effect locus is stable in the symmetric case, there exists no analytical predictions on how this polymorphism holds when a polygenic background also contributes to the trait. Here we propose to answer this question by introducing a new eco-evo methodology that allows us to take into account the combined contributions of a major-effect locus and of a quantitative background resulting from small-effect loci, where inheritance is encoded according to an extension to the infinitesimal model. In a regime of small variance contributed by the quantitative loci, we justify that traits are concentrated around the major alleles, according to a normal distribution, using new convex analysis arguments. This allows a reduction in the complexity of the system using a separation of time scales approach. We predict an undocumented phenomenon of loss of polymorphism at the major-effect locus despite strong selection for local adaptation, because the quantitative background slowly disrupts the rapidly established polymorphism at the major-effect locus, which is confirmed by individual-based simulations. Our study highlights how segregation of a quantitative background can greatly impact the dynamics of major-effect loci by provoking migrational meltdowns.

q-bio.PE

Mathematical Modeling of Cell Collective Motion Triggered By Self-Generated Gradients

Self-generated gradients have atttracted a lot of attention in the recent biological literature. It is considered as a robust strategy for a group of cells to find its way during a long journey. This note is intended to discuss various scenarios for modeling traveling waves of cells that constantly deplete a chemical cue, and so create their own signaling gradient all along the way. We begin with one famous model by Keller and Segel for bacterial chemotaxis. We present the model and the construction of the traveling wave solutions. We also discuss the limitation of this approach, and review some subsequent work addressing stability issues. Next, we review two relevant extensions, which are supported by biological experiments. They both admit traveling wave solutions with an explicit value for the wave speed. We conclude by discussing some open problems and perspectives, and particularly a striking mechanism of speed determinacy occurring at the back of the wave. All the results presented in this note are illustrated by numerical simulations.

math.AP

Ergodicity of the Fisher infinitesimal model with quadratic selection

We study the convergence towards a unique equilibrium distribution of the solutions to a time-discrete model with non-overlapping generations arising in quantitative genetics. The model describes the dynamics of a phenotypic distribution with respect to a multi-dimensional trait, which is shaped by selection and Fisher's infinitesimal model of sexual reproduction. We extend some previous works devoted to the time-continuous analogues, that followed a perturbative approach in the regime of weak selection, by exploiting the contractivity of the infinitesimal model operator in the Wasserstein metric. Here, we tackle the case of quadratic selection by a global approach. We establish uniqueness of the equilibrium distribution and exponential convergence of the renormalized profile. Our technique relies on an accurate control of the propagation of information across the large binary trees of ancestors (the pedigree chart), and reveals an ergodicity property, meaning that the shape of the initial datum is quickly forgotten across generations. We combine this information with appropriate estimates for the emergence of Gaussian tails and propagation of quadratic and exponential moments to derive quantitative convergence rates. Our result can be interpreted as a generalization of the Krein-Rutman theorem in a genuinely non-linear, and non-monotone setting.

math.PR

Dynamics of lineages in adaptation to a gradual environmental change

We investigate a simple quantitative genetics model subjet to a gradual environmental change from the viewpoint of the phylogenies of the living individuals. We aim to understand better how the past traits of their ancestors are shaped by the adaptation to the varying environment. The individuals are characterized by a one-dimensional trait. The dynamics -- births and deaths -- depend on a time-changing mortality rate that shifts the optimal trait to the right at constant speed. The population size is regulated by a nonlinear non-local logistic competition term. The macroscopic behaviour can be described by a PDE that admits a unique positive stationary solution. In the stationary regime, the population can persist, but with a lag in the trait distribution due to the environmental change. For the microscopic (individual-based) stochastic process, the evolution of the lineages can be traced back using the historical process, that is, a measure-valued process on the set of continuous real functions of time. Assuming stationarity of the trait distribution, we describe the limiting distribution, in large populations, of the path of an individual drawn at random at a given time $T$. Freezing the non-linearity due to competition allows the use of a many-to-one identity together with Feynman-Kac's formula. This path, in reversed time, remains close to a simple Ornstein-Uhlenbeck process. It shows how the lagged bulk of the present population stems from ancestors once optimal in trait but still in the tail of the trait distribution in which they lived.

math.PR

Nonlinear stability of chemotactic clustering with discontinuous advection

We perform the nonlinear stability analysis of a chemotaxis model of bacterial self-organization, assuming that bacteria respond sharply to chemical signals. The resulting discontinuous advection speed represents the key challenge for the stability analysis. We follow a perturbative approach, where the shape of the cellular profile is clearly separated from its global motion, allowing us to circumvent the discontinuity issue. Further, the homogeneity of the problem leads to two conservation laws, which express themselves in differently weighted functional spaces. This discrepancy between the weights represents another key methodological challenge. We derive an improved Poincar\'e inequality that allows to transfer the information encoded in the conservation laws to the appropriately weighted spaces. As a result, we obtain exponential relaxation to equilibrium with an explicit rate. A numerical investigation illustrates our results.

math.AP

Horizontal gene transfer: numerical comparison between stochastic and deterministic approaches

Horizontal gene Transfer (HT) denotes the transmission of genetic material between two living organisms, while the vertical transmission refers to a DNA transfer from parents to their offspring. Consistent experimental evidence report that this phenomenon plays an essential role in the evolution of certain bacterias. In particular, HT is believed to be the main instrument of developing the antibiotic resistance. In this work, we consider several models which describe this phenomenon: a stochastic jump process (individual-based) and the deterministic nonlinear integrod-ifferential equation obtained as a limit for large populations. We also consider a Hamilton-Jacobi equation, obtained as a limit of the deterministic model under the assumption of small mutations. The goal of this paper is to compare these models with the help of numerical simulations. More specifically, our goal is to understand to which extent the Hamilton-Jacobi model reproduces the qualitative behavior of the stochastic model and the phenomenon of evolutionary rescue in particular.

q-bio.PE

Uniqueness of stationary states for singular Keller-Segel type models

We consider a generalised Keller-Segel model with non-linear porous medium type diffusion and non-local attractive power law interaction, focusing on potentials that are more singular than Newtonian interaction. We show uniqueness of stationary states (if they exist) in any dimension both in the diffusion-dominated regime and in the fair-competition regime when attraction and repulsion are in balance. As stationary states are radially symmetric decreasing, the question of uniqueness reduces to the radial setting. Our key result is a sharp generalised Hardy-Littlewood-Sobolev type functional inequality in the radial setting.

math.AP

Catch me if you can: a spatial model for a brake-driven gene drive reversal

Population management using artificial gene drives (alleles biasing inheritance, increasing their own transmission to offspring) is becoming a realistic possibility with the development of CRISPR-Cas genetic engineering. A gene drive may however have to be stopped. "Antidotes" (brakes) have been suggested, but have been so far only studied in well-mixed populations. Here, we consider a reaction--diffusion system modeling the release of a gene drive (of fitness $1-a$) and a brake (fitness $1-b$, $b\leq a$) in a wild-type population (fitness $1$). We prove that, whenever the drive fitness is at most $1/2$ while the brake fitness is close to $1$, coextinction of the brake and the drive occurs in the long run. On the contrary, if the drive fitness is greater than $1/2$, then coextinction is impossible: the drive and the brake keep spreading spatially, leaving in the invasion wake a complicated spatio-temporally heterogeneous genetic pattern. Based on numerical experiments, we argue in favor of a global coextinction conjecture provided the drive fitness is at most $1/2$, irrespective of the brake fitness. The proof relies upon the study of a related predator--prey system with strong Allee effect on the prey. Our results indicate that some drives may be unstoppable, and that, if gene drives are ever deployed in nature, threshold drives, that only spread if introduced in high enough frequencies, should be preferred.

math.AP

A well-balanced scheme for chemotactic travelling waves at the mesoscopic scale

We investigate numerically a model consisting in a kinetic equation for the biased motion of bacteria following a run-and-tumble process, coupled with two reaction-diffusion equations for chemical signals. This model exhibits asymptotic propagation at a constant speed. In particular, it admits travelling wave solutions. To capture this propagation, we propose a well-balanced numerical scheme based on Case's elementary solutions for the kinetic equation, and L-splines for the parabolic equations. We use this scheme to explore the Cauchy problem for various parameters. Some examples far from the diffusive regime lead to the coexistence of two waves travelling at different speeds. Numerical tests support the hypothesis that they are both locally asymptotically stable. Interestingly, the exploration of the bifurcation diagram raises counter-intuitive features.

math.AP

Concentration waves of chemotactic bacteria: the discrete velocity case

The existence of travelling waves for a coupled system of hyperbolic/ parabolic equations is established in the case of a finite number of velocities in the kinetic equation. This finds application in collective motion of chemotactic bacteria. The analysis builds on the previous work by the first author (arXiv:1607.00429) in the case of a continuum of velocities. Here, the proof is specific to the discrete setting, based on the decomposition of the population density in special Case's modes. Some counter-intuitive results are discussed numerically, including the coexistence of several travelling waves for some sets of parameters, as well as the possible non-existence of travelling waves.

math.AP

Asymptotic analysis of a quantitative genetics model withnonlinear integral operator

We study the asymptotic behavior of stationary solutions to a quantitative genetics model with trait-dependent mortality and sexual reproduction. The infinitesimal model accounts for the mixing of parental phenotypes at birth.Our asymptotic analysis encompasses the case when deviations between the offspring and the mean parental trait are typically small. Under suitable regularity and growth conditions on the mortality rate, we prove existence and local uniqueness of a stationary profile that get concentrated around a local optimum of mortality, with a Gaussian shape having small variance. Our approach is based on perturbative analysis techniques that require to describe accurately the correction to the Gaussian leading order profile. Our result extends previous results obtained with an asexual mode of reproduction, but using an alternative methodology.

math.AP

Non-local competition slows down front acceleration during dispersal evolution

We investigate the super-linear spreading in a reaction-diffusion model analogous to the Fisher-KPP equation, but in which the population is heterogeneous with respect to the dispersal ability of individuals, and the saturation factor is non-local with respect to one variable. We prove that the rate of acceleration is slower than the rate of acceleration predicted by the linear problem, that is, without saturation. This hindering phenomenon is the consequence of a subtle interplay between the non-local saturation and the non-trivial dynamics of some particular curves that carry the mass at the front. A careful analysis of these trajectories allows us to identify the value of the rate of acceleration. The article is complemented with numerical simulations that illustrate some behavior of the model that is beyond our analysis.

math.AP

Uniqueness of the viscosity solution of a constrained Hamilton-Jacobi equation

In quantitative genetics, viscosity solutions of Hamilton-Jacobi equations appear naturally in the asymptotic limit of selection-mutation models when the population variance vanishes. They have to be solved together with an unknown function I(t) that arises as the counterpart of a non-negativity constraint on the solution at each time. Although the uniqueness of viscosity solutions is known for many variants of Hamilton-Jacobi equations, the uniqueness for this particular type of constrained problem was not resolved, except in a few particular cases. Here, we provide a general answer to the uniqueness problem, based on three main assumptions: convexity of the Hamiltonian function H(I, x, p) with respect to p, monotonicity of H with respect to I, and BV regularity of I(t).

math.AP