Putting theory to the test: An integrated computational/experimental chemostat model of the tragedy of the commons.

Cooperation via shared public goods is ubiquitous in nature, however, noncontributing social cheaters can exploit the public goods provided by cooperating individuals to gain a fitness advantage. Theory predicts that this dynamic can cause a Tragedy of the Commons, and in particular, a 'Collapsing' Tragedy defined as the extinction of the entire population if the public good is essential. However, there is little empirical evidence of the Collapsing Tragedy in evolutionary biology. Here, we experimentally demonstrate this outcome in a microbial model system, the public good-producing bacterium Pseudomonas aeruginosa grown in a continuous-culture chemostat. In a growth medium that requires extracellular protein digestion, we find that P. aeruginosa populations maintain a high density when entirely composed of cooperating, protease-producing cells but completely collapse when non-producing cheater cells are introduced. We formulate a mechanistic mathematical model that recapitulates experimental observations and suggests key parameters, such as the dilution rate and the cost of public good production, that define the stability of cooperative behavior. We combine model prediction with experimental validation to explain striking differences in the long-term cheater trajectories of replicate cocultures through mutational events that increase cheater fitness. Taken together, our integrated empirical and theoretical approach validates and parametrizes the Collapsing Tragedy in a microbial population, and provides a quantitative, mechanistic framework for generating testable predictions of social behavior.

Global analysis of a predator-prey model with variable predator search rate.

We consider a modified Holling-type II predator-prey model, based on the premise that the search rate of predators is dependent on the prey density, rather than constant. A complete analysis of the global behavior of the model is presented, and shows that the model exhibits a dichotomy similar to the classical Holling-type II model: either the coexistence steady state is globally stable; or it is unstable, and then a unique, globally stable limit cycle exists. We discuss the similarities, but also important differences between our model and the Holling-type II model. The main differences are that: 1. The paradox of enrichment which always occurs in the Holling-type II model, does not always occur here, and 2. Even when the paradox of enrichment occurs, predators can adapt by lowering their search rate, and effectively stabilize the system.

Division of labor in bacterial populations.

Cooperating behaviors abound across all domains of life, but are vulnerable to invasion by cheaters. An important evolutionary question is to determine mechanisms that stabilize and maintain cooperation levels and prevent population collapse. Policing is one strategy populations may employ to achieve this goal, and it has been observed in many natural populations including microbes. Here we present and analyze a division of labor model to investigate if, when and how policing can be a cooperation-stabilizing mediator. The model represents a chemostat where cooperators produce a public good that benefits all individuals, and where toxin-producers produce a toxin that harms both cooperators and cheaters. We show that in many cases, the mere presence of toxin-producers is not enough to avoid a Tragedy of the Commons in which all individuals go extinct. The main focus of our work is to identify conditions on various model parameters which ensure that a mixed population of cooperators and toxin-producers can stably coexist and can avoid invasion by a cheater population. This happens when all of the following conditions hold: (i) The cost of policing must exceed the cost of cooperation. (ii) There is enough "collateral damage" caused by policing, i.e. the toxicity rate experienced by cooperators is sufficiently high, and (iii) The toxin affects cheaters even more than cooperators, and we provide a precise mathematical condition of how much stronger this effect should be.

Dispersal Kernels may be Scalable: Implications from a Plant Pathogen.

AIM: Understanding how spatial scale of study affects observed dispersal patterns can provide insights into spatiotemporal population dynamics, particularly in systems with significant long-distance dispersal (LDD). We aimed to investigate the dispersal gradients of two rusts of wheat with spores of similar size, mass, and shape, over multiple spatial scales. We hypothesized that a single dispersal kernel could fit the dispersal from all spatial scales well, and that it would be possible to obtain similar results in spatiotemporal increase of disease when modeling based on differing scales. LOCATION: Central Oregon and St. Croix Island. TAXA: Puccinia striiformis f. sp. tritici, Puccinia graminis f. sp. tritici, Triticum aestivum. METHODS: We compared empirically-derived primary disease gradients of cereal rust across three spatial scales: local (inoculum source and sampling unit = 0.0254 m, spatial extent = 1.52m) field-wide (inoculum source = 1.52 m, sampling unit = 0.305 m, and spatial extent = 91.44 m), and regional (inoculum source and sampling unit = 152 m, spatial extent = 10.7 km). We then examined whether disease spread in spatially explicit simulations depended upon the scale at which data were collected by constructing a compartmental time-step model. RESULTS: The three data sets could be fit well by a single inverse-power law dispersal kernel. Simulating epidemic spread at different spatial resolutions resulted in similar patterns of spatiotemporal spread. Dispersal kernel data obtained at one spatial scale can be used to represent spatiotemporal disease spread at a larger spatial scale. MAIN CONCLUSIONS: Organisms spread by aerially dispersed small propagules that exhibit LDD may follow similar dispersal patterns over a several hundred- or thousand-fold expanse of spatial scale. Given that the primary mechanisms driving aerial dispersal remain constant, it may be possible to extrapolate across scales when empirical data are unavailable at a scale of interest.

Critical thresholds for eventual extinction in randomly disturbed population growth models.

This paper considers several single species growth models featuring a carrying capacity, which are subject to random disturbances that lead to instantaneous population reduction at the disturbance times. This is motivated in part by growing concerns about the impacts of climate change. Our main goal is to understand whether or not the species can persist in the long run. We consider the discrete-time stochastic process obtained by sampling the system immediately after the disturbances, and find various thresholds for several modes of convergence of this discrete process, including thresholds for the absence or existence of a positively supported invariant distribution. These thresholds are given explicitly in terms of the intensity and frequency of the disturbances on the one hand, and the population's growth characteristics on the other. We also perform a similar threshold analysis for the original continuous-time stochastic process, and obtain a formula that allows us to express the invariant distribution for this continuous-time process in terms of the invariant distribution of the discrete-time process, and vice versa. Examples illustrate that these distributions can differ, and this sends a cautionary message to practitioners who wish to parameterize these and related models using field data. Our analysis relies heavily on a particular feature shared by all the deterministic growth models considered here, namely that their solutions exhibit an exponentially weighted averaging property between a function of the initial condition, and the same function applied to the carrying capacity. This property is due to the fact that these systems can be transformed into affine systems.

Tragedy of the commons in the chemostat.

We present a proof of principle for the phenomenon of the tragedy of the commons that is at the center of many theories on the evolution of cooperation. Whereas the tragedy is commonly set in a game theoretical context, and attributed to an underlying Prisoner's Dilemma, we take an alternative approach based on basic mechanistic principles of species growth that does not rely on the specification of payoffs which may be difficult to determine in practice. We establish the tragedy in the context of a general chemostat model with two species, the cooperator and the cheater. Both species have the same growth rate function and yield constant, but the cooperator allocates a portion of the nutrient uptake towards the production of a public good -the "Commons" in the Tragedy- which is needed to digest the externally supplied nutrient. The cheater on the other hand does not produce this enzyme, and allocates all nutrient uptake towards its own growth. We prove that when the cheater is present initially, both the cooperator and the cheater will eventually go extinct, hereby confirming the occurrence of the tragedy. We also show that without the cheater, the cooperator can survive indefinitely, provided that at least a low level of public good or processed nutrient is available initially. Our results provide a predictive framework for the analysis of cooperator-cheater dynamics in a powerful model system of experimental evolution.

High mortality and enhanced recovery: modelling the countervailing effects of disturbance on population dynamics.

Disturbances cause high mortality in populations while simultaneously enhancing population growth by improving habitats. These countervailing effects make it difficult to predict population dynamics following disturbance events. To address this challenge, we derived a novel form of the logistic growth equation that permits time-varying carrying capacity and growth rate. We combined this equation with concepts drawn from disturbance ecology to create a general model for population dynamics in disturbance-prone systems. A river flooding example using three insect species (a fast life-cycle mayfly, a slow life-cycle dragonfly and an ostracod) found optimal tradeoffs between disturbance frequency vs. magnitude and a close fit to empirical data in 62% of cases. A savanna fire analysis identified fire frequencies of 3-4 years that maximised population size of a perennial grass. The model shows promise for predicting population dynamics after multiple disturbance events and for management of river flows and fire regimes.

The puzzle of partial migration: Adaptive dynamics and evolutionary game theory perspectives.

We consider the phenomenon of partial migration which is exhibited by populations in which some individuals migrate between habitats during their lifetime, but others do not. First, using an adaptive dynamics approach, we show that partial migration can be explained on the basis of negative density dependence in the per capita fertilities alone, provided that this density dependence is attenuated for increasing abundances of the subtypes that make up the population. We present an exact formula for the optimal proportion of migrants which is expressed in terms of the vital rates of migrant and non-migrant subtypes only. We show that this allocation strategy is both an evolutionary stable strategy (ESS) as well as a convergence stable strategy (CSS). To establish the former, we generalize the classical notion of an ESS because it is based on invasion exponents obtained from linearization arguments, which fail to capture the stabilizing effects of the nonlinear density dependence. These results clarify precisely when the notion of a "weak ESS", as proposed in Lundberg (2013) for a related model, is a genuine ESS. Secondly, we use an evolutionary game theory approach, and confirm, once again, that partial migration can be attributed to negative density dependence alone. In this context, the result holds even when density dependence is not attenuated. In this case, the optimal allocation strategy towards migrants is the same as the ESS stemming from the analysis based on the adaptive dynamics. The key feature of the population models considered here is that they are monotone dynamical systems, which enables a rather comprehensive mathematical analysis.

The abundant marine bacterium Pelagibacter simultaneously catabolizes dimethylsulfoniopropionate to the gases dimethyl sulfide and methanethiol.

Marine phytoplankton produce ∼10(9) tonnes of dimethylsulfoniopropionate (DMSP) per year(1,2), an estimated 10% of which is catabolized by bacteria through the DMSP cleavage pathway to the climatically active gas dimethyl sulfide(3,4). SAR11 Alphaproteobacteria (order Pelagibacterales), the most abundant chemo-organotrophic bacteria in the oceans, have been shown to assimilate DMSP into biomass, thereby supplying this cell's unusual requirement for reduced sulfur(5,6). Here, we report that Pelagibacter HTCC1062 produces the gas methanethiol, and that a second DMSP catabolic pathway, mediated by a cupin-like DMSP lyase, DddK, simultaneously shunts as much as 59% of DMSP uptake to dimethyl sulfide production. We propose a model in which the allocation of DMSP between these pathways is kinetically controlled to release increasing amounts of dimethyl sulfide as the supply of DMSP exceeds cellular sulfur demands for biosynthesis.

Parasite sources and sinks in a patched Ross-Macdonald malaria model with human and mosquito movement: Implications for control.

We consider the dynamics of a mosquito-transmitted pathogen in a multi-patch Ross-Macdonald malaria model with mobile human hosts, mobile vectors, and a heterogeneous environment. We show the existence of a globally stable steady state, and a threshold that determines whether a pathogen is either absent from all patches, or endemic and present at some level in all patches. Each patch is characterized by a local basic reproduction number, whose value predicts whether the disease is cleared or not when the patch is isolated: patches are known as "demographic sinks" if they have a local basic reproduction number less than one, and hence would clear the disease if isolated; patches with a basic reproduction number above one would sustain endemic infection in isolation, and become "demographic sources" of parasites when connected to other patches. Sources are also considered focal areas of transmission for the larger landscape, as they export excess parasites to other areas and can sustain parasite populations. We show how to determine the various basic reproduction numbers from steady state estimates in the patched network and knowledge of additional model parameters, hereby identifying parasite sources in the process. This is useful in the context of control of the infection on natural landscapes, because a commonly suggested strategy is to target focal areas, in order to make their corresponding basic reproduction numbers less than one, effectively turning them into sinks. We show that this is indeed a successful control strategy-albeit a conservative and possibly expensive one-in case either the human host, or the vector does not move. However, we also show that when both humans and vectors move, this strategy may fail, depending on the specific movement patterns exhibited by hosts and vectors.

The effectiveness of marine protected areas for predator and prey with varying mobility.

Marine protected areas (MPAs) are regions in the ocean where fishing is restricted or prohibited. Although several measures for MPA performance exist, here we focus on a specific one, namely the ratio of the steady state fish densities inside and outside the MPA. Several 2 patch models are proposed and analyzed mathematically. One patch represents the MPA, whereas the second patch represents the fishing ground. Fish move freely between both regions in a diffusive manner. Our main objective is to understand how fish mobility affects MPA performance. We show that MPA effectiveness decreases with fish mobility for single species models with logistic growth, and that densities inside and outside the MPA tend to equalize. This suggests that MPA performance is highest for the least mobile species. We then consider a 2 patch Lotka-Volterra predator-prey system. When one of the species moves, and the other does not, the ratio of the moving species first remains constant, and ultimately decreases with increased fish mobility, again with a tendency of equalization of the density in both regions. This suggests that MPA performance is not only highest for slow, but also for moderately mobile species. The discrepancy in MPA performance for single species models and for predator-prey models, confirms that MPA design requires an integrated, ecosystem-based approach. The mathematical approaches advocated here complement and enhance the numerical and theoretical approaches that are commonly applied to more complex models in the context of MPA design.

Traveling waves in response to a diffusing quorum sensing signal in spatially-extended bacterial colonies.

In the behavior known as quorum sensing (QS), bacteria release diffusible signal molecules known as autoinducers, which by accumulating in the environment induce population-wide changes in gene expression. Although QS has been extensively studied in well-mixed systems, the ability of diffusing QS signals to synchronize gene expression in spatially extended colonies is not well understood. Here we investigate the one-dimensional spatial propagation of QS-circuit activation in a simple, analytically tractable reaction-diffusion model for the LuxR-LuxI circuit, which regulates bioluminescence of the marine bacterium Aliivibrio fischeri. The quorum activation loop is modeled by a Hill function with a cooperativity exponent (m=2.2). The model is parameterized from laboratory data and captures the major empirical properties of the LuxR-LuxI system and its QS regulation of A. fischeri bioluminescence. Our simulations of the model show propagating waves of activation or deactivation of the QS circuit in a spatially extended colony. We further prove analytically that the model equations possess a traveling wave solution. This mathematical proof yields the rate of autoinducer degradation that is compatible with a traveling wave of gene expression as well as the critical degradation rate at which the nature of the wave switches from activation to deactivation. Our results can be used to predict the direction and activating or deactivating nature of a wave of gene expression in experimentally controlled bacterial populations subject to a diffusing autoinducer signal.

Dynamical models explaining social balance and evolution of cooperation.

Social networks with positive and negative links often split into two antagonistic factions. Examples of such a split abound: revolutionaries versus an old regime, Republicans versus Democrats, Axis versus Allies during the second world war, or the Western versus the Eastern bloc during the Cold War. Although this structure, known as social balance, is well understood, it is not clear how such factions emerge. An earlier model could explain the formation of such factions if reputations were assumed to be symmetric. We show this is not the case for non-symmetric reputations, and propose an alternative model which (almost) always leads to social balance, thereby explaining the tendency of social networks to split into two factions. In addition, the alternative model may lead to cooperation when faced with defectors, contrary to the earlier model. The difference between the two models may be understood in terms of the underlying gossiping mechanism: whereas the earlier model assumed that an individual adjusts his opinion about somebody by gossiping about that person with everybody in the network, we assume instead that the individual gossips with that person about everybody. It turns out that the alternative model is able to lead to cooperative behaviour, unlike the previous model.

Instability in a generalized Keller-Segel model.

We present a generalized Keller-Segel model where an arbitrary number of chemical compounds react, some of which are produced by a species, and one of which is a chemoattractant for the species. To investigate the stability of homogeneous stationary states of this generalized model, we consider the eigenvalues of a linearized system. We are able to reduce this infinite dimensional eigenproblem to a parametrized finite dimensional eigenproblem. By matrix theoretic tools, we then provide easily verifiable sufficient conditions for destabilizing the homogeneous stationary states. In particular, one of the sufficient conditions is that the chemotactic feedback is sufficiently strong. Although this mechanism was already known to exist in the original Keller-Segel model, here we show that it is more generally applicable by significantly enlarging the class of models exhibiting this instability phenomenon which may lead to pattern formation.

Quorum activation at a distance: spatiotemporal patterns of gene regulation from diffusion of an autoinducer signal.

Quorum sensing (QS) bacteria regulate gene expression collectively by exchanging diffusible signal molecules known as autoinducers. Although QS is often studied in well-stirred laboratory cultures, QS bacteria colonize many physically and chemically heterogeneous environments where signal molecules are transported primarily by diffusion. This raises questions of the effective distance range of QS and the degree to which colony behavior can be synchronized over such distances. We have combined experiments and modeling to investigate the spatiotemporal patterns of gene expression that develop in response to a diffusing autoinducer signal. We embedded a QS strain in a narrow agar lane and introduced exogenous autoinducer at one terminus of the lane. We then measured the expression of a QS reporter as a function of space and time as the autoinducer diffused along the lane. The diffusing signal readily activates the reporter over distances of ~1 cm on time scales of ~10 h. However, the patterns of activation are qualitatively unlike the familiar spreading patterns of simple diffusion, as the kinetics of response are surprisingly insensitive to the distance the signal has traveled. We were able to reproduce these patterns with a mathematical model that combines simple diffusion of the signal with logistic growth of the bacteria and cooperative activation of the reporter. In a wild-type QS strain, we also observed the propagation of a unique spatiotemporal excitation. Our results show that a chemical signal transported only by diffusion can be remarkably effective in synchronizing gene expression over macroscopic distances.

Paradoxical suppression of poly-specific broadly neutralizing antibodies in the presence of strain-specific neutralizing antibodies following HIV infection.

One of the first immunologic responses against HIV infection is the presence of neutralizing antibodies that seem able to inactivate several HIV strains. Moreover, in vitro studies have shown the existence of monoclonal antibodies that exhibit broad crossclade neutralizing potential. Yet their number is low and slow to develop in vivo. In this paper, we investigate the potential benefits of inducing poly-specific neutralizing antibodies in vivo throughout immunization. We develop a mathematical model that considers the activation of families of B lymphocytes producing poly-specific and strain-specific antibodies and use it to demonstrate that, even if such families are successful in producing neutralizing antibodies, the competition between them may limit the poly-specific response allowing the virus to escape. We modify this model to account for viral evolution under the pressure of antibody responses in natural HIV infection. The model can reproduce viral escape under certain conditions of B lymphocyte competition. Using these models we provide explanations for the observed antibody failure in controlling natural infection and predict quantitative measures that need to be satisfied for long-term control of HIV infection.

Graph-theoretic characterizations of monotonicity of chemical networks in reaction coordinates.

This paper derives new results for certain classes of chemical reaction networks, linking structural to dynamical properties. In particular, it investigates their monotonicity and convergence under the assumption that the rates of the reactions are monotone functions of the concentrations of their reactants. This is satisfied for, yet not restricted to, the most common choices of the reaction kinetics such as mass action, Michaelis-Menten and Hill kinetics. The key idea is to find an alternative representation under which the resulting system is monotone. As a simple example, the paper shows that a phosphorylation/dephosphorylation process, which is involved in many signaling cascades, has a global stability property. We also provide a global stability result for a more complicated example that describes a regulatory pathway of a prevalent signal transduction module, the MAPK cascade.

The chemostat with lateral gene transfer.

We investigate the standard chemostat model when lateral gene transfer is taken into account. We will show that when the different genotypes have growth rate functions that are sufficiently close to a common growth rate function, and when the yields of the genotypes are sufficiently close to a common value, then the population evolves to a globally stable steady state, at which all genotypes coexist. These results can explain why the antibiotic-resistant strains persist in the pathogen population.

Senescence and antibiotic resistance in an age-structured population model.

Different theories have been proposed to understand the growing problem of antibiotic resistance of microbial populations. Here we investigate a model that is based on the hypothesis that senescence is a possible explanation for the existence of so-called persister cells which are resistant to antibiotic treatment. We study a chemostat model with a microbial population which is age-structured and show that if the growth rates of cells in different age classes are sufficiently close to a scalar multiple of a common growth rate, then the population will globally stabilize at a coexistence steady state. This steady state persists under an antibiotic treatment if the level of antibiotics is below a certain threshold; if the level exceeds this threshold, the washout state becomes a globally attracting equilibrium.