Invasion and adaptive evolution for individual-based spatially structured populations

The interplay between space and evolution is an important issue in population dynamics, that is in particular crucial in the emergence of polymorphism and spatial patterns. Recently, biological studies suggest that invasion and evolution are closely related. Here we model the interplay between space and evolution starting with an individual-based approach and show the important role of parameter scalings on clustering and invasion. We consider a stochastic discrete model with birth, death, competition, mutation and spatial diffusion, where all the parameters may depend both on the position and on the trait of individuals. The spatial motion is driven by a reflected diffusion in a bounded domain. The interaction is modelled as a trait competition between individuals within a given spatial interaction range. First, we give an algorithmic construction of the process. Next, we obtain large population approximations, as weak solutions of nonlinear reaction-diffusion equations with Neumann's boundary conditions. As the spatial interaction range is fixed, the nonlinearity is nonlocal. Then, we make the interaction range decrease to zero and prove the convergence to spatially localized nonlinear reaction-diffusion equations, with Neumann's boundary conditions. Finally, simulations based on the microscopic individual-based model are given, illustrating the strong effects of the spatial interaction range on the emergence of spatial and phenotypic diversity (clustering and polymorphism) and on the interplay between invasion and evolution. The simulations focus on the qualitative differences between local and nonlocal interactions

The impact of cell crowding and active cell movement on vascular tumour growth

A multiscale model for vascular tumour growth is presented which includes systems of ordinary differential equations for the cell cycle and regulation of apoptosis in individual cells, coupled to partial differential equations for the spatio-temporal dynamics of nutrient and key signalling chemicals. Furthermore, these subcellular and tissue layers are incorporated into a cellular automaton framework for cancerous and normal tissue with an embedded vascular network. The model is the extension of previous work and includes novel features such as cell movement and contact inhibition. We presented a detailed simulation study of the effects of these additions on the invasive behaviour of tumour cells and the tumour's response to chemotherapy. In particular, we find that cell movement alone increases the rate of tumour growth and expansion, but that increasing the tumour cell carrying capacity leads to the formation of less invasive dense hypoxic tumours containing fewer tumour cells. However, when an increased carrying capacity is combined with significant tumour cell movement, the tumour grows and spreads more rapidly, accompanied by large spatio-temporal fluctuations in hypoxia, and hence in the number of quiescent cells. Since, in the model, hypoxic/quiescent cells produce VEGF which stimulates vascular adaptation, such fluctuations can dramatically affect drug delivery and the degree of success of chemotherapy

On the variations of the principal eigenvalue with respect to a parameter in growth-fragmentation models

We study the variations of the principal eigenvalue associated to a growth-fragmentation-death equation with respect to a parameter acting on growth and fragmentation. To this aim, we use the probabilistic individual-based interpretation of the model. We study the variations of the survival probability of the stochastic model, using a generation by generation approach. Then, making use of the link between the survival probability and the principal eigenvalue established in a previous work, we deduce the variations of the eigenvalue with respect to the parameter of the model

Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

Adaptive dynamics in logistic branching populations

We consider a trait-structured population subject to mutation, birth and competition of logistic type, where the number of coexisting types may fluctuate. Applying a limit of rare mutations to this population while keeping the population size finite leads to a jump process, the so-called `trait substitution sequence', where evolution proceeds by successive invasions and fixations of mutant types. The probability of fixation of a mutant is interpreted as a fitness landscape that depends on the current state of the population. It was in adaptive dynamics that this kind of model was first invented and studied, under the additional assumption of large population. Assuming also small mutation steps, adaptive dynamics' theory provides a deterministic ODE approximating the evolutionary dynamics of the dominant trait of the population, called `canonical equation of adaptive dynamics'. In this work, we want to include genetic drift in this models by keeping the population finite. Rescaling mutation steps (weak selection) yields in this case a diffusion on the trait space that we call `canonical diffusion of adaptive dynamics', in which genetic drift (diffusive term) is combined with directional selection (deterministic term) driven by the fitness gradient. Finally, in order to compute the coefficients of this diffusion, we seek explicit first-order formulae for the probability of fixation of a nearly neutral mutant appearing in a resident population. These formulae are expressed in terms of `invasibility coefficients' associated with fertility, defense, aggressiveness and isolation, which measure the robustness (stability w.r.t. selective strengths) of the resident type. Some numerical results on the canonical diffusion are also given

A systematic approach to cancer: evolution beyond selection.

Cancer is typically scrutinized as a pathological process characterized by chromosomal aberrations and clonal expansion subject to stochastic Darwinian selection within adaptive cellular ecosystems. Cognition based evolution is suggested as an alternative approach to cancer development and progression in which neoplastic cells of differing karyotypes and cellular lineages are assessed as self-referential agencies with purposive participation within tissue microenvironments. As distinct self-aware entities, neoplastic cells occupy unique participant/observer status within tissue ecologies. In consequence, neoplastic proliferation by clonal lineages is enhanced by the advantaged utilization of ecological resources through flexible re-connection with progenitor evolutionary stages

Evolution of discrete populations and the canonical diffusion of adaptive dynamics

The biological theory of adaptive dynamics proposes a description of the long-term evolution of a structured asexual population. It is based on the assumptions of large population, rare mutations and small mutation steps, that lead to a deterministic ODE describing the evolution of the dominant type, called the ``canonical equation of adaptive dynamics.'' Here, in order to include the effect of stochasticity (genetic drift), we consider self-regulated randomly fluctuating populations subject to mutation, so that the number of coexisting types may fluctuate. We apply a limit of rare mutations to these populations, while keeping the population size finite. This leads to a jump process, the so-called ``trait substitution sequence,'' where evolution proceeds by successive invasions and fixations of mutant types. Then we apply a limit of small mutation steps (weak selection) to this jump process, that leads to a diffusion process that we call the ``canonical diffusion of adaptive dynamics,'' in which genetic drift is combined with directional selection driven by the gradient of the fixation probability, also interpreted as an invasion fitness. Finally, we study in detail the particular case of multitype logistic branching populations and seek explicit formulae for the invasion fitness of a mutant deviating slightly from the resident type. In particular, second-order terms of the fixation probability are products of functions of the initial mutant frequency, times functions of the initial total population size, called the invasibility coefficients of the resident by increased fertility, defence, aggressiveness, isolation or survival.Comment: Published at http://dx.doi.org/10.1214/105051606000000628 in the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org