Transmission rates and adaptive evolution of pathogens in sympatric heterogeneous plant populations

Diversification in agricultural cropping patterns is widely practised to delay the build-up of virulent races that can overcome host resistance in pathogen populations. This can lead to balanced polymorphism, but the long-term consequences of this strategy for the evolution of crop pathogen populations are still unclear. The widespread occurrence of sibling species and reproductively isolated sub-species among fungal and oomycete plant pathogens suggests that evolutionary divergence is common. This paper develops a mathematical model of host-pathogen interactions using a simple framework of two hosts to analyse the influences of sympatric host heterogeneity on the long-term evolutionary behaviour of plant pathogens. Using adaptive dynamics, which assumes that sequential mutations induce small changes in pathogen fitness, we show that evolutionary outcomes strongly depend on the shape of the trade-off curve between pathogen transmission on sympatric hosts. In particular, we determine the conditions under which the evolutionary branching of a monomorphic into a dimorphic population occurs, as well as the conditions that lead to the evolution of specialist (single host range) or generalist (multiple host range) pathogen populations.     

Molecular evolutionary signatures reveal the role of host ecological dynamics in viral disease emergence and spread

RNA viruses account for numerous emerging and perennial infectious diseases, and are characterized by rapid rates of molecular evolution. The ecological dynamics of most emerging RNA viruses are still poorly understood and difficult to ascertain. The availability of genome sequence data for many RNA viruses, in principle, could be used to infer ecological dynamics if changes in population numbers produced a lasting signature within the pattern of genome evolution. As a result, the rapidly emerging phylogeographic structure of a pathogen, shaped by the rise and fall in the number of infections and their spatial distribution, could be used as a surrogate for direct ecological assessments. Based on rabies virus as our example, we use a model combining ecological and evolutionary processes to test whether variation in the rate of host movement results in predictive diagnostic patterns of pathogen genetic structure. We identify several linearizable relationships between host dispersal rate and measures of phylogenetic structure suggesting genetic information can be used to directly infer ecological process. We also find phylogenetic structure may be more revealing than demography for certain ecological processes. Our approach extends the reach of current analytic frameworks for infectious disease dynamics by linking phylogeography back to underlying ecological processes.     

Bacterial pathogen evolution: breaking news

The immense social and economic impact of bacterial pathogens, from drug-resistant infections in hospitals to the devastation of agricultural resources, has resulted in major investment to understand the causes and consequences of pathogen evolution. Recent genome sequencing projects have provided insight into the evolution of bacterial genome structures; revealing the impact of mobile DNA on genome restructuring and pathogenicity. Sequencing of multiple genomes of related strains has enabled the delineation of pathogen evolution and facilitated the tracking of bacterial pathogens globally. Other recent theoretical and empirical studies have shown that pathogen evolution is significantly influenced by ecological factors, such as the distribution of hosts within the environment and the effects of co-infection. We suggest that the time is ripe for experimentalists to use genomics in conjunction with evolutionary ecology experiments to further understanding of how bacterial pathogens evolve.     

The influence of host demography, pathogen virulence, and relationships with pathogen virulence on the evolution of pathogen transmission in a spatial context

A major challenge in evolutionary ecology is to explain extensive natural variation in transmission rates and virulence across pathogens. Host and pathogen ecology is a potentially important source of that variation. Theory of its effects has been developed through the study of non-spatial models, but host population spatial structure has been shown to influence evolutionary outcomes. To date, the effects of basic host and pathogen demography on pathogen evolution have not been thoroughly explored in a spatial context. Here we use simulations to show that space produces novel predictions of the influence of the shape of the pathogen’s transmission–virulence tradeoff, as well as host reproduction and mortality, on the pathogen’s evolutionary stable transmission rate. Importantly, non-spatial models predict that neither the slope of linear transmission–virulence relationships, nor the host reproduction rate will influence pathogen evolution, and that host mortality will only influence it when there is a transmission–virulence tradeoff. We show that this is not the case in a spatial context, and identify the ecological conditions under which spatial effects are most influential. Thus, these results may help explain observed natural variation among pathogens unexplainable by non-spatial models, and provide guidance about when space should be considered. We additionally evaluate the ability of existing analytical approaches to predict the influence of ecology, namely spatial moment equations closed with an improved pair approximation (IPA). The IPA is known to have limited accuracy, but here we show that in the context of pathogens the limitations are substantial: in many cases, IPA incorrectly predicts evolution to pathogen-driven extinction. Despite these limitations, we suggest that the impact of ecology can still be understood within the conceptual framework arising from spatial moment equations, that of “self-shading’’, whereby the spread of highly transmissible pathogens is impeded by local depletion of susceptible hosts.     

On the evolutionary dynamics of pathogens with direct and environmental transmission

A number of ecologically and economically important pathogens exhibit a complex transmission dynamics that involves distinct transmission modes. In this paper, we study the evolutionary dynamics of pathogens for which transmission includes direct host-to-host as well as indirect environmental transmission. Different routes of infection spread require specific adaptations of the parasite, which may result in conflicting selection pressures. Using the framework of Adaptive dynamics, we investigate how these conflicting selection pressures are resolved in the course of evolution and determine the conditions for evolutionary diversification of pathogen strains. We show that evolutionary branching and subsequent evolution of specialist strains occurs in wide parameter regions but evolutionary bistability and evolution of generalist pathogens are possible as well. Our analysis reveals that the relative contributions of direct and environmental transmission, as well as the underlying ecological dynamics, play a crucial role in shaping the course of pathogen evolution. Our findings may explain the coexistence of high and low virulence strains observed in several pathogenic organisms using different transmission modes (e.g., influenza viruses) and highlight the importance of considering ecological dynamics in virulence management.     

Functional genomics of bacterial pathogens: from post-genomics to therapeutic targets

A wealth of new data have become available to the scientific community as a result of the sequencing of many pathogen genomes. A recent meeting devoted to functional genomics of pathogenic microorganisms confirmed the notion that bacterial genomes are not static, because large blocks of genes can be acquired or deleted. Less complex environments usually result in reduction in genome size, while genome expansion is usually associated with environmental change and complexity. During the meeting, pathogenicity and evolutionary aspects were illustrated for enteric pathogens, as well as the microevolution of the plague bacillus Yersinia pestis. New clues for evolution and pathogenicity were derived from comparative genomics of Listeria species. The genomic organization of Bartonellae, an emerging human pathogen, was also discussed in an evolutionary context. Population and functional genomics of Anthrax-causing bacteria highlighted current scientific interest in this potential biothreat.     

Spatial pattern switching enables cyclic evolution in spatial epidemics

Infectious diseases often spread as spatial epidemic outbreak waves. A number of model studies have shown that such spatial pattern formation can have important consequences for the evolution of pathogens. Here, we show that such spatial patterns can cause cyclic evolutionary dynamics in selection for the length of the infectious period. The necessary reversal in the direction of selection is enabled by a qualitative change in the spatial pattern from epidemic waves to irregular local outbreaks. The spatial patterns are an emergent property of the epidemic system, and they are robust against changes in specific model assumptions. Our results indicate that emergent spatial patterns can act as a rich source for complexity in pathogen evolution.     

The origin of human pathogens: evaluating the role of agriculture and domestic animals in the evolution of human disease

Many significant diseases of human civilization are thought to have arisen concurrently with the advent of agriculture in human society. It has been hypothesised that the food produced by farming increased population sizes to allow the maintenance of virulent pathogens, i.e. civilization pathogens, while domestic animals provided sources of disease to humans. To determine the relationship between pathogens in humans and domestic animals, I examined phylogenetic data for several human pathogens that are commonly evolutionarily linked to domestic animals: measles, pertussis, smallpox, tuberculosis, taenid worms, and falciparal malaria. The majority are civilization pathogens, although I have included others whose evolutionary origins have traditionally been ascribed to domestic animals. The strongest evidence for a domestic-animal origin exists for measles and pertussis, although the data do not exclude a non-domestic origin. As for the other pathogens, the evidence currently available makes it difficult to determine if the domestic-origin hypothesis is supported or refuted; in fact, intriguing data for tuberculosis and taenid worms suggests that transmission may occur as easily from humans to domestic animals. These findings do not abrogate the importance of agriculture in disease transmission; rather, if anything, they suggest an alternative, more complex series of effects than previously elucidated. Rather than domestication, the broader force for human pathogen evolution could be ecological change, namely anthropogenic modification of the environment. This is supported by evidence that many current emerging infectious diseases are associated with human modification of the environment. Agriculture may have changed the transmission ecology of pre-existing human pathogens, increased the success of pre-existing pathogen vectors, resulted in novel interactions between humans and wildlife, and, through the domestication of animals, provided a stable conduit for human infection by wildlife diseases.     

Ecological and evolutionary drivers of haemoplasma infection and bacterial genotype sharing in a Neotropical bat community

Most emerging pathogens can infect multiple species, underlining the importance of understanding the ecological and evolutionary factors that allow some hosts to harbour greater infection prevalence and share pathogens with other species. However, our understanding of pathogen jumps is based primarily around viruses, despite bacteria accounting for the greatest proportion of zoonoses. Because bacterial pathogens in bats (order Chiroptera) can have conservation and human health consequences, studies that examine the ecological and evolutionary drivers of bacterial prevalence and barriers to pathogen sharing are crucially needed. Here were studied haemotropic Mycoplasma spp. (i.e., haemoplasmas) across a species‐rich bat community in Belize over two years. Across 469 bats spanning 33 species, half of individuals and two‐thirds of species were haemoplasma positive. Infection prevalence was higher for males and for species with larger body mass and colony sizes. Haemoplasmas displayed high genetic diversity (21 novel genotypes) and strong host specificity. Evolutionary patterns supported codivergence of bats and bacterial genotypes alongside phylogenetically constrained host shifts. Bat species centrality to the network of shared haemoplasma genotypes was phylogenetically clustered and unrelated to prevalence, further suggesting rare—but detectable—bacterial sharing between species. Our study highlights the importance of using fine phylogenetic scales when assessing host specificity and suggests phylogenetic similarity may play a key role in host shifts not only for viruses but also for bacteria. Such work more broadly contributes to increasing efforts to understand cross‐species transmission and the epidemiological consequences of bacterial pathogens.     

There's something afoot in the evolution of ontogenies

Allometry, the association between size and shape, has long been considered an evolutionary constraint because of its ability to channel variation in particular directions in response to evolution of size. Several recent studies, however, have demonstrated that allometries themselves can evolve. Therefore, constraints based on these allometries are not constant over long evolutionary time scales. The changes in ontogeny appear to have a clear adaptive basis, which establishes a feedback loop from adaptive change of ontogeny through the altered developmental constraints to the potential for further evolutionary change. Altogether, therefore, this new evidence underscores the tight interactions between developmental and ecological factors in the evolution of morphological traits.     

Climate change accelerates local disease extinction rates in a long‐term wild host–pathogen association

Pathogens are a significant component of all plant communities. In recent years, the potential for existing and emerging pathogens of agricultural crops to cause increased yield losses as a consequence of changing climatic patterns has raised considerable concern. In contrast, the response of naturally occurring, endemic pathogens to a warming climate has received little attention. Here, we report on the impact of a signature variable of global climate change – increasing temperature – on the long‐term epidemiology of a natural host–pathogen association involving the rust pathogen Triphragmium ulmariae and its host plant Filipendula ulmaria. In a host–pathogen metapopulation involving approximately 230 host populations growing on an archipelago of islands in the Gulf of Bothnia we assessed changes in host population size and pathogen epidemiological measures over a 25‐year period. We show how the incidence of disease and its severity declines over that period and most importantly demonstrate a positive association between a long‐term trend of increasing extinction rates in individual pathogen populations of the metapopulation and increasing temperature. Our results are highly suggestive that changing climatic patterns, particularly mean monthly growing season (April‐November) temperature, are markedly influencing the epidemiology of plant disease in this host–pathogen association. Given the important role plant pathogens have in shaping the structure of communities, changes in the epidemiology of pathogens have potentially far‐reaching impacts on ecological and evolutionary processes. For these reasons, it is essential to increase understanding of pathogen epidemiology, its response to warming, and to invoke these responses in forecasts for the future.     

Targets of selection in a disease resistance network in wild tomatoes

Studies combining comparative genomics and information on biochemical pathways have revealed that protein evolution can be affected by the amount of pleiotropy associated with a particular gene. The amount of pleiotropy, in turn, can be a function of the position at which a gene operates in a pathway and the pathway structure. Genes that serve as convergence points and have several partners (so-called hubs) often show the greatest constraint and hence the slowest rate of protein evolution. In this article, we have studied five genes (Pto, Fen, Rin4, Prf and Pfi) in a defence signalling network in a wild tomato species, Solanum peruvianum. These proteins operate together and contribute to bacterial resistance in tomato. We predicted that Prf (and possibly Pfi), which serves as a convergence point for upstream signals, should show greater evolutionary constraint. However, we found instead that two of the genes which potentially interact with pathogen ligands, Rin4 and Fen, have evolved under strong evolutionary constraint, whereas Prf and Pfi, which probably function further downstream in the network, show evidence of balancing selection. This counterintuitive observation may be probable in pathogen defence networks, because pathogens may target positions throughout resistance networks to manipulate or nullify host resistance, thereby leaving a molecular signature of host-parasite co-evolution throughout a single network.     

Increased susceptibility to fungal disease accompanies adaptation to drought in Brassica rapa

Recent studies have demonstrated adaptive evolutionary responses to climate change, but little is known about how these responses may influence ecological interactions with other organisms, including natural enemies. We used a resurrection experiment in the greenhouse to examine the effect of evolutionary responses to drought on the susceptibility of Brassica rapa plants to a fungal pathogen, Alternaria brassicae. In agreement with previous studies in this population, we found an evolutionary shift to earlier flowering postdrought, which was previously shown to be adaptive. Here, we report the novel finding that postdrought descendant plants were also more susceptible to disease, indicating a rapid evolutionary shift to increased susceptibility. This was accompanied by an evolutionary shift to increased specific leaf area (thinner leaves) following drought. We found that flowering time and disease susceptibility displayed plastic responses to experimental drought treatments, but that this plasticity did not match the direction of evolution, indicating that plastic and evolutionary responses to changes in climate can be opposed. The observed evolutionary shift to increased disease susceptibility accompanying adaptation to drought provides evidence that even if populations can rapidly adapt in response to climate change, evolution in other traits may have ecological effects that could make species more vulnerable.     

Evolution of virulence: triggering host inflammation allows invading pathogens to exclude competitors

Virulence is generally considered to benefit parasites by enhancing resource-transfer from host to pathogen. Here, we offer an alternative framework where virulent immune-provoking behaviours and enhanced immune resistance are joint tactics of invading pathogens to eliminate resident competitors (transferring resources from resident to invading pathogen). The pathogen wins by creating a novel immunological challenge to which it is already adapted. We analyse a general ecological model of 'proactive invasion' where invaders not adapted to a local environment can succeed by changing it to one where they are better adapted than residents. However, the two-trait nature of the 'proactive' strategy (provocation of, and adaptation to environmental change) presents an evolutionary conundrum, as neither trait alone is favoured in a homogenous host population. We show that this conundrum can be resolved by allowing for host heterogeneity. We relate our model to emerging empirical findings on immunological mediation of parasite competition.     

Developing insect models for the study of current and emerging human pathogens

The study of human diseases requires the testing of microorganisms in model systems. Although mammals are typically used, we argue the validity of using insects as models in order to examine human diseases, particularly the growing number of opportunistic microorganisms. Insects can be used in large numbers, are easily manipulated, and are not subject to the same ethical concerns as mammalian systems. Insects and mammals have many parallels with respect to microbial pathogenesis, from proteinaceous integuments that require breaching before infection to similarities in their innate immune responses. Reactions of insects to Candida and Pseudomonas spp. infections show good correlation with mouse models, providing precedent-setting examples of the study of human pathogens using insects. Insects as pathogen hosts also warrant study because they may act as reservoirs for emerging human pathogens. Finally, insect models may be used to examine the evolutionary processes involved in the acquisition of virulence factors and host-jumping mechanisms indispensable to emerging pathogens. Insect models may be used in 'niche' investigations where large sample sizes can facilitate rapid, informative screening of opportunistic diseases and provide insights into pathogen evolution, while reducing the cost and ethical concerns associated with mammalian models.     

Specific resistance prevents the evolution of general resistance and facilitates disease emergence

Host-shifts, where pathogens jump from an ancestral host to a novel host, can be facilitated or impeded by standing variation in disease resistance, but only if resistance provides broad-spectrum general resistance against multiple pathogen species. Host resistance comes in many forms and includes both general resistance, as well as specific resistance, which may only be effective against a single pathogen species or even genotype. However, most evolutionary models consider only one of these forms of resistance, and we have less understanding of how these two forms of resistance evolve in tandem. Here, we develop a model that allows for the joint evolution of specific and general resistance and asks if the evolution of specific resistance drives a decrease in the evolution of general resistance. We also explore how these evolutionary outcomes affect the risk of foreign pathogen invasion and persistence. We show that in the presence of a single endemic pathogen, the two forms of resistance are strongly exclusionary. Critically, we find that specific resistance polymorphisms can prevent the evolution of general resistance, facilitating the invasion of foreign pathogens. We also show that specific resistance polymorphisms are a necessary condition for the successful establishment of foreign pathogens following invasion, as they prevent the exclusion of the foreign pathogen by the more transmissible endemic pathogen. Our results demonstrate the importance of considering the joint evolution of multiple forms of resistance when evaluating a population's susceptibility to foreign pathogens.     

Cheating, trade-offs and the evolution of aggressiveness in a natural pathogen population

The evolutionary dynamics of pathogens are critically important for disease outcomes, prevalence and emergence. In this study we investigate ecological conditions that may promote the long-term maintenance of virulence polymorphisms in pathogen populations. Recent theory predicts that evolution towards increased virulence can be reversed if less-aggressive social 'cheats' exploit more aggressive 'cooperator' pathogens. However, there is no evidence that social exploitation operates within natural pathogen populations. We show that for the bacterium Pseudomonas syringae, major polymorphisms for pathogenicity are maintained at unexpectedly high frequencies in populations infecting the host Arabidopsis thaliana. Experiments reveal that less-aggressive strains substantially increase their growth potential in mixed infections and have a fitness advantage in non-host environments. These results suggest that niche differentiation can contribute to the maintenance of virulence polymorphisms, and that both within-host and between-host growth rates modulate cheating and cooperation in P. syringae populations.     

Evolution of Pathogen Specialisation in a Host Metapopulation: Joint Effects of Host and Pathogen Dispersal

Metapopulation processes are important determinants of epidemiological and evolutionary dynamics in host-pathogen systems, and are therefore central to explaining observed patterns of disease or genetic diversity. In particular, the spatial scale of interactions between pathogens and their hosts is of primary importance because migration rates of one species can affect both spatial and temporal heterogeneity of selection on the other. In this study we developed a stochastic and discrete time simulation model to specifically examine the joint effects of host and pathogen dispersal on the evolution of pathogen specialisation in a spatially explicit metapopulation. We consider a plant-pathogen system in which the host metapopulation is composed of two plant genotypes. The pathogen is dispersed by air-borne spores on the host metapopulation. The pathogen population is characterised by a single life-history trait under selection, the infection efficacy. We found that restricted host dispersal can lead to high amount of pathogen diversity and that the extent of pathogen specialisation varied according to the spatial scale of host-pathogen dispersal. We also discuss the role of population asynchrony in determining pathogen evolutionary outcomes.     

The evolutionary genomics of pathogen recombination

A pressing problem in studying the evolution of microbial pathogens is to determine the extent to which these genomes recombine. This information is essential for locating pathogenicity loci by using association studies or population genetic approaches. Recombination also complicates the use of phylogenetic approaches to estimate evolutionary parameters such as selection pressures. Reliable methods that detect and estimate the rate of recombination are, therefore, vital. This article reviews the approaches that are available for detecting and estimating recombination in microbial pathogens and how they can be used to understand pathogen evolution and to identify medically relevant loci.