Cue-driven microbial cooperation and communication: evolving quorum sensing with honest signaling.

BACKGROUND: Quorum sensing (QS) is the ability of microorganisms to assess local clonal density by measuring the extracellular concentration of signal molecules that they produce and excrete. QS is also the only known way of bacterial communication that supports the coordination of within-clone cooperative actions requiring a certain threshold density of cooperating cells. Cooperation aided by QS communication is sensitive to cheating in two different ways: laggards may benefit from not investing in cooperation but enjoying the benefit provided by their cooperating neighbors, whereas Liars explicitly promise cooperation but fail to do so, thereby convincing potential cooperating neighbors to help them, for almost free. Given this double vulnerability to cheats, it is not trivial why QS-supported cooperation is so widespread among prokaryotes. RESULTS: We investigated the evolutionary dynamics of QS in populations of cooperators for whom the QS signal is an inevitable side effect of producing the public good itself (cue-based QS). Using spatially explicit agent-based lattice simulations of QS-aided threshold cooperation (whereby cooperation is effective only above a critical cumulative level of contributions) and three different (analytical and numerical) approximations of the lattice model, we explored the dynamics of QS-aided threshold cooperation under a feasible range of parameter values. We demonstrate three major advantages of cue-driven cooperation. First, laggards cannot wipe out cooperation under a wide range of reasonable environmental conditions, in spite of an unconstrained possibility to mutate to cheating; in fact, cooperators may even exclude laggards at high cooperation thresholds. Second, lying almost never pays off, if the signal is an inevitable byproduct (i.e., the cue) of cooperation; even very cheap fake signals are selected against. And thirdly, QS is most useful if local cooperator densities are the least predictable, i.e., if their lattice-wise mean is close to the cooperation threshold with a substantial variance. CONCLUSIONS: Comparing the results of the four different modeling approaches indicates that cue-driven threshold cooperation may be a viable evolutionary strategy for microbes that cannot keep track of past behavior of their potential cooperating partners, in spatially viscous and in well-mixed environments alike. Our model can be seen as a version of the famous greenbeard effect, where greenbeards coexist with defectors in a evolutionarily stable polymorphism. Such polymorphism is maintained by the condition-dependent trade-offs of signal production which are characteristic of cue-based QS.

Cooperation in public goods game does not require assortment and depends on population density.

The threshold public goods game is one of the best-known models of non-linear public goods dilemmas. Cooperators and defectors typically coexist in this game when the population is assumed to follow the so-called structured deme model. In this article, we develop a dynamical model of a general N-player game in which there is no deme structure: Individuals interact with randomly chosen neighbours and selection occurs between randomly chosen pairs of individuals. We show that in the deterministic limit, the dynamics in this model leads to the same replicator dynamics as in the structured deme model, i.e., coexistence of cooperators and defectors is typical in threshold public goods game even when the population is completely well mixed. We extend the model to study the effect of density dependence and density fluctuation on the dynamics. We show analytically and numerically that decreasing population density increases the equilibrium frequency of cooperators till the fixation of this strategy, but below a critical density cooperators abruptly disappear from the population. Our numerical investigations show that weak density fluctuations enhance cooperation, while strong fluctuations suppress it.

The Ecology of Spider Sociality: A Spatial Model.

AbstractThe emergence of animal societies offers unsolved problems for both evolutionary and ecological studies. Social spiders are especially well suited to address this problem given their multiple independent origins and distinct geographic distribution. On the basis of long-term research on the spider genus Anelosimus, we developed a spatial model that re-creates observed macroecological patterns in the distribution of social and subsocial spiders. We show that parallel gradients of increasing insect size and disturbance (rain, predation) with proximity to the lowland tropical rain forest would explain why social species are concentrated in the lowland wet tropics but absent from higher elevations and latitudes. The model further shows that disturbance, which disproportionately affects small colonies, not only creates conditions that require group living but also tempers the dynamics of large social groups. Similarly simple underlying processes, albeit with different players on a somewhat different stage, may explain the diversity of other social systems.

Weak selection helps cheap but harms expensive cooperation in spatial threshold dilemmas.

Public Goods Games (PGGs) are n-person games with dependence of individual fitness benefits on the collective investment by the players. We have studied a simple PGG scenario played out by cooperating (C) and defecting (D) agents, applying the highly nonlinear threshold benefit function in an individual-based lattice model. A semi-analytical approximation of the lattice model has been developed and shown to describe the dynamics fairly well in the vicinity of the steady state. Besides the expected outcomes (i.e., the negative effect on cooperator persistence of higher cooperation costs and/or more intensive mixing of the population) we have found a surprising, counter-intuitive effect of the strength of selection on the steady state of the model. The effect is different at low and high cooperation costs, and it shows up only in the lattice model, suggesting that stochastic effects and higher order spatial correlations due to the emergent spatial clustering of cooperators (not taken into account in the semi-analytical approximation) must be responsible for the unexpected results for which we propose an intuitive explanation, present a tentative demonstration, and shortly discuss their biological relevance.

Transition from growth to decay of an epidemic due to lockdown.

We study the transition of an epidemic from growth phase to decay of the active infections in a population when lockdown health measures are introduced to reduce the probability of disease transmission. Although in the case of uniform lockdown, a simple compartmental model would indicate instantaneous transition to decay of the epidemic, this is not the case when partially isolated active clusters remain with the potential to create a series of small outbreaks. We model this using the Gillespie stochastic simulation algorithm based on a connected set of stochastic susceptible-infected-removed/recovered networks representing the locked-down majority population (in which the reproduction number is less than 1) weakly coupled to a large set of small clusters in which the infection may propagate. We find that the presence of such active clusters can lead to slower than expected decay of the epidemic and significantly delayed onset of the decay phase. We study the relative contributions of these changes, caused by the active clusters within the population, to the additional total infected population. We also demonstrate that limiting the size of the inevitable active clusters can be efficient in reducing their impact on the overall size of the epidemic outbreak. The deceleration of the decay phase becomes apparent when the active clusters form at least 5% of the population.

Efficient assembly and long-term stability of defensive microbiomes via private resources and community bistability.

Understanding the mechanisms that promote the assembly and maintenance of host-beneficial microbiomes is an open problem. Empirical evidence supports the idea that animal and plant hosts can combine 'private resources' with the ecological phenomenon known as 'community bistability' to favour some microbial strains over others. We briefly review evidence showing that hosts can: (i) protect the growth of beneficial strains in an isolated habitat, (ii) use antibiotics to suppress non-beneficial, competitor strains, and (iii) provide resources that only beneficial strains are able to translate into an increased rate of growth, reproduction, or antibiotic production. We then demonstrate in a spatially explicit, individual-based model that these three mechanisms act similarly by selectively promoting the initial proliferation of preferred strains, that is, by acting as a private resource. The faster early growth of preferred strains, combined with the phenomenon of 'community bistability,' allows those strains to continue to dominate the microbiome even after the private resource is withdrawn or made public. This is because after a beneficial colony reaches a sufficiently large size, it can resist invasion by parasites without further private support from the host. We further explicitly model localized microbial interactions and diffusion dynamics, and we show that an intermediate level of antibiotic diffusion is the most efficient mechanism in promoting preferred strains and that there is a wide range of parameters under which hosts can promote the assembly of a self-sustaining defensive microbiome. This in turn supports the idea that hosts readily evolve to promote host-beneficial defensive microbiomes.

Analysis of stability to cheaters in models of antibiotic degrading microbial communities.

Antibiotic resistance carried out by antibiotic degradation has been suggested recently as a new mechanism to maintain coexistence of microbial species competing on a single limiting resource, even in well-mixed homogeneous environments. Species diversity and community stability, however, critically depend on resistance against social cheaters, mutants that do not invest in production, but still enjoy the benefits provided by others. Here we investigate how different mutant cheaters affect the stability of antibiotic producing and degrading microbial communities. We consider two cheater types, production and degradation cheaters. We generalize the mixed inhibition-zone and chemostat models introduced previously [Kelsic, E. D., Zhao, J., Vetsigian, K., Kishony, R., 2015. Counteraction of an tibiotic production and degradation stabilizes microbial communities. Nature521, 516-519.] to study the population dynamics of microbial communities in well-mixed environment, and analyze the invasion of different cheaters in these models. We show that production cheaters, mutants that cease producing antibiotics, always destroy coexistence whenever there is a cost of producing these antibiotics. Degradation cheaters, mutants that loose their function of producing extracellular antibiotic degrading molecules, induce community collapse only if the cost of producing the degradation factors is above a critical level. Our analytical studies, supported by numerical simulations, highlight the sensitivity of antibiotic producing and degrading communities to loss-of-function mutants.

Evolution of optimal Hill coefficients in nonlinear public goods games.

In evolutionary game theory, the effect of public goods like diffusible molecules has been modelled using linear, concave, sigmoid and step functions. The observation that biological systems are often sigmoid input-output functions, as described by the Hill equation, suggests that a sigmoid function is more realistic. The Michaelis-Menten model of enzyme kinetics, however, predicts a concave function, and while mechanistic explanations of sigmoid kinetics exist, we lack an adaptive explanation: what is the evolutionary advantage of a sigmoid benefit function? We analyse public goods games in which the shape of the benefit function can evolve, in order to determine the optimal and evolutionarily stable Hill coefficients. We find that, while the dynamics depends on whether output is controlled at the level of the individual or the population, intermediate or high Hill coefficients often evolve, leading to sigmoid input-output functions that for some parameters are so steep to resemble a step function (an on-off switch). Our results suggest that, even when the shape of the benefit function is unknown, biological public goods should be modelled using a sigmoid or step function rather than a linear or concave function.

Trading public goods stabilizes interspecific mutualism.

The existence of cooperation between species raises a fundamental problem for evolutionary theory. Why provide costly services to another species if the feedback of this provision also happens to benefit intra-specific competitors that provide no service? Rewarding cooperators and punishing defectors can help maintain mutualism; this is not possible, however, when one can only respond to the collective action of one's partners, which is likely to be the case in many common symbioses. We show how the theory of public goods can explain the stability of mutualism when discrimination between cooperators and defectors is not possible: if two groups of individuals trade goods that are non-linear, increasing functions of the number of contributions, their mutualistic interaction is maintained by the exchange of these public goods, even when it is not possible to punish defectors, which can persist at relatively high frequencies. This provides a theoretical justification and testable predictions for the evolution of mutualism in the absence of discrimination mechanisms.

Strategy diversity stabilizes mutualism through investment cycles, phase polymorphism, and spatial bubbles.

There is continuing interest in understanding factors that facilitate the evolution and stability of cooperation within and between species. Such interactions will often involve plasticity in investment behavior, in response to the interacting partner's investments. Our aim here is to investigate the evolution and stability of reciprocal investment behavior in interspecific interactions, a key phenomenon strongly supported by experimental observations. In particular, we present a comprehensive analysis of a continuous reciprocal investment game between mutualists, both in well-mixed and spatially structured populations, and we demonstrate a series of novel mechanisms for maintaining interspecific mutualism. We demonstrate that mutualistic partners invariably follow investment cycles, during which mutualism first increases, before both partners eventually reduce their investments to zero, so that these cycles always conclude with full defection. We show that the key mechanism for stabilizing mutualism is phase polymorphism along the investment cycle. Although mutualistic partners perpetually change their strategies, the community-level distribution of investment levels becomes stationary. In spatially structured populations, the maintenance of polymorphism is further facilitated by dynamic mosaic structures, in which mutualistic partners form expanding and collapsing spatial bubbles or clusters. Additionally, we reveal strategy-diversity thresholds, both for well-mixed and spatially structured mutualistic communities, and discuss factors for meeting these thresholds, and thus maintaining mutualism. Our results demonstrate that interspecific mutualism, when considered as plastic investment behavior, can be unstable, and, in agreement with empirical observations, may involve a polymorphism of investment levels, varying both in space and in time. Identifying the mechanisms maintaining such polymorphism, and hence mutualism in natural communities, provides a significant step towards understanding the coevolution and population dynamics of mutualistic interactions.

How to assemble a beneficial microbiome in three easy steps.

There is great interest in explaining how beneficial microbiomes are assembled. Antibiotic-producing microbiomes are arguably the most abundant class of beneficial microbiome in nature, having been found on corals, arthropods, molluscs, vertebrates and plant rhizospheres. An exemplar is the attine ants, which cultivate a fungus for food and host a cuticular microbiome that releases antibiotics to defend the fungus from parasites. One explanation posits long-term vertical transmission of Pseudonocardia bacteria, which (somehow) evolve new compounds in arms-race fashion against parasites. Alternatively, attines (somehow) selectively recruit multiple, non-coevolved actinobacterial genera from the soil, enabling a 'multi-drug' strategy against parasites. We reconcile the models by showing that when hosts fuel interference competition by providing abundant resources, the interference competition favours the recruitment of antibiotic-producing (and -resistant) bacteria. This partner-choice mechanism is more effective when at least one actinobacterial symbiont is vertically transmitted or has a high immigration rate, as in disease-suppressive soils.

Review: Game theory of public goods in one-shot social dilemmas without assortment.

We review the theory of public goods in biology. In the N-person prisoner's dilemma, where the public good is a linear function of the individual contributions, cooperation requires some form of assortment, for example due to kin discrimination, population viscosity or repeated interactions. In most social species ranging from bacteria to humans, however, public goods are usually a non-linear function of the contributions, which makes cooperation possible without assortment. More specifically, a polymorphic state can be stable in which cooperators and non-cooperators coexist. The existence of mixed equilibria in public goods games is a fundamental result in the study of cooperation that has been overlooked so far, because of the disproportionate attention given to the two- and N-person prisoner's dilemma. Methods and results from games with pairwise interactions or linear benefits cannot, in general, be extended to the analysis of public goods. Game theory helps explain the production of public goods in one-shot, N-person interactions without assortment, it leads to predictions that can be easily tested and allows a prescriptive approach to cooperation.

A strategic model of a host-microbe-microbe system reveals the importance of a joint host-microbe immune response to combat stress-induced gut dysbiosis.

Microbiomes provide key ecological functions to their host; however, most host-associated microbiomes are too complicated to allow a model of essential host-microbe-microbe interactions. The intestinal microbiota of salmonids may offer a solution since few dominating species often characterize it. Healthy fish coexist with a mutualistic Mycoplasma sp. species, while stress allows the spread of pathogenic strains, such as Aliivibrio sp. Even after a skin infection, the Mycoplasma does not recover; Aliivibrio sp. often remains the dominant species, or Mycoplasma-Aliivibrio coexistence was occasionally observed. We devised a model involving interactions among the host immune system, Mycoplasma sp. plus a toxin-producing pathogen. Our model embraces a complete microbiota community and is in harmony with experimental results that host-Mycoplasma mutualism prevents the spread of pathogens. Contrary, stress suppresses the host immune system allowing dominance of pathogens, and Mycoplasma does not recover after stress disappears.

Economic game theory for mutualism and cooperation.

We review recent work at the interface of economic game theory and evolutionary biology that provides new insights into the evolution of partner choice, host sanctions, partner fidelity feedback and public goods. (1) The theory of games with asymmetrical information shows that the right incentives allow hosts to screen-out parasites and screen-in mutualists, explaining successful partner choice in the absence of signalling. Applications range from ant-plants to microbiomes. (2) Contract theory distinguishes two longstanding but weakly differentiated explanations of host response to defectors: host sanctions and partner fidelity feedback. Host traits that selectively punish misbehaving symbionts are parsimoniously interpreted as pre-adaptations. Yucca-moth and legume-rhizobia mutualisms are argued to be examples of partner fidelity feedback. (3) The theory of public goods shows that cooperation in multi-player interactions can evolve in the absence of assortment, in one-shot social dilemmas among non-kin. Applications include alarm calls in vertebrates and exoenzymes in microbes.

Density-dependent private benefit leads to bacterial mutualism.

Microorganisms produce and secrete materials that are beneficial for themselves and their neighbors. We modeled the situation when cells can produce different costly secretions which increase the carrying capacity of the population. Strains that lose the function of producing one or more secretions avoid the cost of production and can exhaust the producers. However, secreting substances provides a private benefit for the producers in a density-dependent way. We developed a model to examine the outcome of the selection among different types of producer strains from the nonproducer strain to the partial producers, to the full producer strain. We were interested in circumstances under which selection maintains partners that produce complementary secreted materials thus forming an interdependent mutualistic interaction. We show that interdependent mutualism is selected under a broad range of conditions if private benefit decreases with density. Selection frequently causes the coexistence of more and less generalist cooperative strains, thus cooperation and exploitation co-occur. Interdependent mutualism is evolved under more specific circumstances if private benefit increases with density and these general observations are valid in a well-mixed and a structured deme model. We show that the applied population structure allows the invasion of rare cooperators and supports cooperation in general.

Effects of social distancing on the spreading of COVID-19 inferred from mobile phone data.

A better understanding of how the COVID-19 pandemic responds to social distancing efforts is required for the control of future outbreaks and to calibrate partial lock-downs. We present quantitative relationships between key parameters characterizing the COVID-19 epidemiology and social distancing efforts of nine selected European countries. Epidemiological parameters were extracted from the number of daily deaths data, while mitigation efforts are estimated from mobile phone tracking data. The decrease of the basic reproductive number ([Formula: see text]) as well as the duration of the initial exponential expansion phase of the epidemic strongly correlates with the magnitude of mobility reduction. Utilizing these relationships we decipher the relative impact of the timing and the extent of social distancing on the total death burden of the pandemic.

Degree of anisogamy is unrelated to the intensity of sexual selection.

Males and females often display different behaviours and, in the context of reproduction, these behaviours are labelled sex roles. The Darwin-Bateman paradigm argues that the root of these differences is anisogamy (i.e., differences in size and/or function of gametes between the sexes) that leads to biased sexual selection, and sex differences in parental care and body size. This evolutionary cascade, however, is contentious since some of the underpinning assumptions have been questioned. Here we investigate the relationships between anisogamy, sexual size dimorphism, sex difference in parental care and intensity of sexual selection using phylogenetic comparative analyses of 64 species from a wide range of animal taxa. The results question the first step of the Darwin-Bateman paradigm, as the extent of anisogamy does not appear to predict the intensity of sexual selection. The only significant predictor of sexual selection is the relative inputs of males and females into the care of offspring. We propose that ecological factors, life-history and demography have more substantial impacts on contemporary sex roles than the differences of gametic investments between the sexes.

Cooperators Unite! Assortative linking promotes cooperation particularly for medium sized associations.

BACKGROUND: Evolution of cooperative behaviour is widely studied in different models where interaction is heterogeneous, although static among individuals. However, in nature individuals can often recognize each other and chose, besides to cooperate or not, to preferentially associate with or to avoid certain individuals.Here we consider a dynamical interaction graph, in contrast to a static one. We propose several rules of rejecting unwanted partners and seeking out new ones, and study the probability of emergence and maintenance of cooperation on these dynamic networks. RESULTS: Our simulations reveal that cooperation can evolve and be stable in the population if we introduce preferential linking, even if defectors can perform it too. The fixation of cooperation has higher probability than that of on static graphs, and this effect is more prevalent at high benefit to cost ratios. We also find an optimal number of partners, for which the fixation probability of cooperation shows a maximum. CONCLUSIONS: The ability to recognize, seek out or avoid interaction partners based on the outcome of past interactions has an important effect on the emergence of cooperation. Observations about the number of partners in natural cooperating groups are in concordance with the result of our model.

The evolution of intermediate castration virulence and ant coexistence in a spatially structured environment.

Theory suggests that spatial structuring should select for intermediate levels of virulence in parasites, but empirical tests are rare and have never been conducted with castration (sterilizing) parasites. To test this theory in a natural landscape, we construct a spatially explicit model of the symbiosis between the ant-plant Cordia nodosa and its two, protecting ant symbionts, Allomerus and Azteca. Allomerus is also a castration parasite, preventing fruiting to increase colony fecundity. Limiting the dispersal of Allomerus and host plant selects for intermediate castration virulence. Increasing the frequency of the mutualist, Azteca, selects for higher castration virulence in Allomerus, because seeds from Azteca-inhabited plants are a public good that Allomerus exploits. These results are consistent with field observations and, to our knowledge, provide the first empirical evidence supporting the hypothesis that spatial structure can reduce castration virulence and the first such evidence in a natural landscape for either mortality or castration virulence.

Evolution of generous cooperative norms by cultural group selection.

Evolution of cooperative norms is studied in a population where individual- and group-level selection are both in operation. Individuals play indirect reciprocity game within their group. Individuals are well informed about the previous actions and reputations, and follow second-order norms. Individuals are norm-followers, and imitate their successful group mates. In contrast to previous models where norms classify actions deterministically, we assume that norms determine only the probabilities of actions, and mutants can differ in these probabilities. The central question is how a selective cooperative norm can emerge in a population where initially only non-cooperative norms were present. It is shown that evolution leads to a cooperative state if generous cooperative strategies are dominant, although the "always defecting" and the "always cooperating"-like strategies remain stably present. The characteristics of these generous cooperative strategies and the presence of always defecting and always cooperating strategies are in concordance with experimental observations.