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.

Microbial biospherics: The experimental study of ecosystem function and evolution.

Awareness that our planet is a self-supporting biosphere with sunlight as its major source of energy for life has resulted in a long-term historical fascination with the workings of self-supporting ecological systems. However, the studies of such systems have never entered the canon of ecological or evolutionary tools and instead, have led a fringe existence connected to life support system engineering and space travel. We here introduce a framework for a renaissance in biospherics based on the study of matter-closed, energy-open ecosystems at a microbial level (microbial biospherics). Recent progress in genomics, robotics, and sensor technology makes the study of closed systems now much more tractable than in the past, and we argue that the time has come to emancipate the study of closed systems from this fringe context and bring them into a mainstream approach for studying ecosystem processes. By permitting highly replicated long-term studies, especially on predetermined and simplified systems, microbial biospheres offer the opportunity to test and develop strong hypotheses about ecosystem function and the ecological and evolutionary determinants of long-term system failure or persistence. Unlike many sciences, ecosystem ecology has never fully embraced a reductionist approach and has remained focused on the natural world in all its complexity. We argue that a reductionist approach to ecosystem ecology, using microbial biospheres, based on a combination of theory and the replicated study of much simpler self-enclosed microsystems could pay huge dividends.

Resistance Correlations Influence Infection by Foreign Pathogens.

AbstractReciprocal selection promotes the specificity of host-pathogen associations and resistance polymorphisms in response to disease. However, plants and animals also vary in response to pathogen species not previously encountered in nature, with potential effects on new disease emergence. Using anther smut disease, we show that resistance (measured as infection rates) to foreign pathogens can be correlated with standing variation in resistance to an endemic pathogen. In Silene vulgaris, genetic variation in resistance to its endemic anther smut pathogen correlated positively with resistance variation to an anther smut pathogen from another host, but the relationship was negative between anther smut and a necrotrophic pathogen. We present models describing the genetic basis for assessing resistance relationships between endemic and foreign pathogens and for quantifying infection probabilities on foreign pathogen introduction. We show that even when the foreign pathogen has a lower average infection ability than the endemic pathogen, infection outcomes are determined by the sign and strength of the regression of the host's genetic variation in infection rates by a foreign pathogen on variation in infection rates by an endemic pathogen as well as by resistance allele frequencies. Given that preinvasion equilibria of resistance are determined by factors including resistance costs, we show that protection against foreign pathogens afforded by positively correlated resistances can be lessened or even result in elevated infection risk at the population level, depending on local dynamics. Therefore, a pathogen's emergence potential could be influenced not only by its average infection rate but also by resistance variation resulting from prior selection imposed by endemic diseases.

Myristate and the ecology of AM fungi: significance, opportunities, applications and challenges.

A recent study by Sugiura and coworkers reported the non-symbiotic growth and spore production of an arbuscular mycorrhizal (AM) fungus, Rhizophagus irregularis, when the fungus received an external supply of certain fatty acids, myristates (C:14). This discovery follows the insight that AM fungi receive fatty acids from their hosts when in symbiosis. If this result holds up and can be repeated under nonsterile conditions and with a broader range of fungi, it has numerous consequences for our understanding of AM fungal ecology, from the level of the fungus, at the plant community level, and to functional consequences in ecosystems. In addition, myristate may open up several avenues from a more applied perspective, including improved fungal culture and supplementation of AM fungi or inoculum in the field. We here map these potential opportunities, and additionally offer thoughts on potential risks of this potentially new technology. Lastly, we discuss the specific research challenges that need to be overcome to come to an understanding of the potential role of myristate in AM ecology.

Evolution of behavioural resistance in host-pathogen systems.

Behavioural resistance to parasites is widespread in animals, yet little is known about the evolutionary dynamics that have shaped these strategies. We show that theory developed for the evolution of physiological parasite resistance can only be applied to behavioural resistance under limited circumstances. We find that accounting explicitly for the behavioural processes, including the detectability of infected individuals, leads to novel dynamics that are strongly dependent on the nature of the costs and benefits of social interactions. As with physiological resistance, evolutionary dynamics of behavioural resistance can also lead to mixed strategies that balance these costs and benefits.

Co-occurrence among three divergent plant-castrating fungi in the same Silene host species.

The competitive exclusion principle postulates that different species can only coexist in sympatry if they occupy distinct ecological niches. The goal of this study was to understand the geographical distribution of three species of Microbotryum anther-smut fungi that are distantly related but infect the same host plants, the sister species Silene vulgaris and S. uniflora, in Western Europe. We used microsatellite markers to investigate pathogen distribution in relation to host specialization and ecological factors. Microbotryum violaceo-irregulare was only found on S. vulgaris at high elevations in the Alps. Microbotryum lagerheimii could be subdivided into two genetically differentiated clusters, one on S. uniflora in the UK and the second on S. vulgaris in the Alps and Pyrenees. The most abundant pathogen species, M. silenes-inflatae, could be subdivided into four genetic clusters, co-occurring in the Alps, the UK and the Pyrenees, and was found on both S. vulgaris and S. uniflora. All three fungal species had high levels of homozygosity, in agreement with the selfing mating system generally observed in anther-smut fungi. The three pathogen species and genetic clusters had large range overlaps, but occurred at sites with different elevations, temperatures and precipitation levels. The three Microbotryum species thus do not appear to be maintained by host specialization or geographic allopatry, but instead may occupy different ecological niches in terms of environmental conditions.

Effect of the anther-smut fungus Microbotryum on the juvenile growth of its host Silene latifolia.

PREMISE OF THE STUDY: Plant pathogens that form persistent systemic infections within plants have the potential to affect multiple plant life history traits, yet we tend to focus only on visible symptoms. Anther smut of Silene latifolia caused by the fungus Microbotryum lychnidis-dioicae induces the anthers of its host to support fungal spore production instead of pollen, and the pathogen is primarily transmitted among flowering plants by pollinators. Nevertheless, most of its life cycle is spent in the asymptomatic vegetative phase, and spores falling on seedlings or nonflowering plants can also infect the host. The purpose of this study was to ask whether the fungus also had an effect on its host plant in the juvenile vegetative phase before flowering as this is important for the disease dynamics in species where infection of seedlings is commonplace. METHODS: Leaf length and leaf number of inoculated and uninoculated juvenile plants were compared in greenhouse experiments, and in one experiment, disease status of the plants at flowering was determined. KEY RESULTS: Inoculated plants had shorter but more leaves, and reduced root mass at the early juvenile (preflowering) stage. Some of these effects were detectable in plants that were inoculated but showed no disease symptoms at flowering. CONCLUSIONS: These results show that pathogenic fungi can have endophyte-like effects even in the total absence of their typical and more charismatic symptoms, and conversely that the assessment of endophyte effects on the fitness of their hosts should include all stages of the host life cycle.

Co-occurrence and hybridization of anther-smut pathogens specialized on Dianthus hosts.

Host specialization has important consequences for the diversification and ecological interactions of obligate pathogens. The anther-smut disease of natural plant populations, caused by Microbotryum fungi, has been characterized by specialized host-pathogen interactions, which contribute in part to the isolation among these numerous fungal species. This study investigated the molecular variation of Microbotryum pathogens within the geographic and host-specific distributions on wild Dianthus species in southern European Alps. In contrast to prior studies on this pathogen genus, a range of overlapping host specificities was observed for four delineated Microbotryum lineages on Dianthus hosts, and their frequent co-occurrence within single-host populations was quantified at local and regional scales. In addition to potential consequences for direct pathogen competition, the sympatry of Microbotryum lineages led to hybridization between them in many populations, and these admixed genotypes suffered significant meiotic sterility. Therefore, this investigation of the anther-smut fungi reveals how variation in the degrees of host specificity can have major implications for ecological interactions and genetic integrity of differentiated pathogen lineages.

A translation of the Linnaean dissertation The Invisible World.

This study presents the first translation from Latin to English of the Linnaean dissertation Mundus invisibilis or The Invisible World, submitted by Johannes Roos in 1769. The dissertation highlights Linnaeus's conviction that infectious diseases could be transmitted by living organisms, too small to be seen. Biographies of Linnaeus often fail to mention that Linnaeus was correct in ascribing the cause of diseases such as measles, smallpox and syphilis to living organisms. The dissertation itself reviews the work of many microscopists, especially on zoophytes and insects, marvelling at the many unexpected discoveries. It then discusses and quotes at length the observations of Münchhausen suggesting that spores from fungi causing plant diseases germinate to produce animalcules, an observation that Linnaeus claimed to have confirmed. The dissertation then draws parallels between these findings and the contagiousness of many human diseases, and urges further studies of this 'invisible world' since, as Roos avers, microscopic organisms may cause more destruction than occurs in all wars.

Interactive effects of root endophytes and arbuscular mycorrhizal fungi on an experimental plant community.

Plant-soil microbial interactions have moved into focus as an important mechanism for understanding plant coexistence and composition of communities. Both arbuscular mycorrhizal (AM) as well as other root endophytic fungi co-occur in plant roots, and therefore have the potential to influence relative abundances of plant species in local assemblages. However, no study has experimentally examined how these key root endosymbiont groups might interact and affect plant community composition. Here, using an assemblage of five plant species in mesocosms in a fully factorial experiment, we added an assemblage of AM fungi and/or a mixture of root endophytic fungal isolates, all obtained from the same grassland field site. The results demonstrate that the AM fungi and root endophytes interact to affect plant community composition by changing relative species abundance, and consequently aboveground productivity. Our study highlights the need to explicitly consider interactions of root-inhabiting fungal groups in studies of plant assemblages.

Early research on anther-smut disease: A fuller view of science?

The anther-smut host-pathogen system has provided extensive insights into the evolutionary ecology of disease resistance, transmission modes, host shifts, pathogen specialization, and disease evolution in metapopulations. It also has led to unexpected insights into sex ratio distorters, sex chromosome evolution, and transposable elements in fungi. In addition, anther-smut disease played a major role in Linnaeus' germ theory and the correspondence on parasitic castration between Darwin and Becker, one of the first female botanists. Here, we explicitly highlight some of the realities in the process of science, using an unusual autobiographical approach to describe how we came to collaborate on this system in the 1980s. Using perspectives from our different career stages, we present a surprising narrative that could not be deduced from merely reading the published papers. While our work was grounded in previous ecological and evolutionary theory, it was the product as much of empirical failures and intellectual roadblocks, as the result of a progressive scientific method. Our experiences illustrate not only the "human dimension of science" but more importantly show that linear sequences of hypothesis testing do not necessarily lead to new study systems and new ideas. We suggest there is a need to re-evaluate the scientific method in ecology and evolution, especially where the challenge is to engage in a productive dialog between natural history and theory.

Anthelmintic treatment alters the parasite community in a wild mouse host.

Individuals are often co-infected with several parasite species, yet the consequences of drug treatment on the dynamics of parasite communities in wild populations have rarely been measured. Here, we experimentally reduced nematode infection in a wild mouse population and measured the effects on other non-target parasites. A single oral dose of the anthelmintic, ivermectin, significantly reduced nematode infection, but resulted in a reciprocal increase in other gastrointestinal parasites, specifically coccidial protozoans and cestodes. These results highlight the possibility that drug therapy may have unintended consequences for non-target parasites and that host-parasite dynamics cannot always be fully understood in the framework of single host-parasite interactions.

Host density shapes the relative contribution of vector-based and aerial transmission of a pathogenic fungus.

Pathogen transmission mode is a key determinant of epidemiological outcomes. Theory shows that host density can influence the spread of pathogens differentially depending on their mode of transmission. Host density could therefore play an important role in determining the pathogen transmission mode. We tested theoretical expectations using floral arrays of the alpine carnation Dianthus pavonius in field experiments of spore dispersal of the anther-smut fungus, Microbotryum, by vector (pollinator)-based floral transmission and passive aerial transmission at a range of host densities. Pollinators deposited fewer spores per plant at high host density than at lower density (ranging from a 0.2-2 m spacing between plants), and vector-based spore deposition at higher densities declined more steeply with distance from diseased plant sources. In contrast, while aerial spore deposition declined with distance from the diseased source, the steepness of this decline was independent of host density. Our study indicates that the amount and distance of vector-based transmission are likely to be a nonmonotonic function of host density as a result of vector behavior, which is not readily encapsulated by fixed dispersal functions. We conclude that the spatial spread of pathogens by vectors is likely to be greater at lower and intermediate densities, whereas the spatial spread of aerially transmitted pathogens would be greater at high densities. These contrasting patterns could lead to differential importance of each transmission mode in terms of its contribution to subsequent infections across host densities.

Host-pathogen coevolution promotes the evolution of general, broad-spectrum resistance and reduces foreign pathogen spillover risk.

Genetic variation for disease resistance within host populations can strongly impact the spread of endemic pathogens. In plants, recent work has shown that within-population variation in resistance can also affect the transmission of foreign spillover pathogens if that resistance is general. However, most hosts also possess specific resistance mechanisms that provide strong defenses against coevolved endemic pathogens. Here we use a modeling approach to ask how antagonistic coevolution between hosts and their endemic pathogen at the specific resistance locus can affect the frequency of general resistance, and therefore a host's vulnerability to foreign pathogens. We develop a two-locus model with variable recombination that incorporates both general resistance (effective against all pathogens) and specific resistance (effective against endemic pathogens only). With coevolution, when pathogens can evolve to evade specific resistance, we find that the regions where general resistance can evolve are greatly expanded, decreasing the risk of foreign pathogen invasion. Furthermore, coevolution greatly expands the conditions that maintain polymorphisms at both resistance loci, thereby driving greater genetic diversity within host populations. This genetic diversity often leads to positive correlations between host resistance to foreign and endemic pathogens, similar to those observed in natural populations. However, if resistance loci become linked, the resistance correlations can shift to negative. If we include a third linkage-modifying locus in our model, we find that selection often favors complete linkage. Our model demonstrates how coevolutionary dynamics with an endemic pathogen can mold the resistance structure of host populations in ways that affect its susceptibility to foreign pathogen spillovers, and that the nature of these outcomes depends on resistance costs, as well as the degree of linkage between resistance genes.

Host-pathogen coevolution promotes the evolution of general, broad-spectrum resistance and reduces foreign pathogen spillover risk.

Genetic variation for disease resistance within host populations can strongly impact the spread of endemic pathogens. In plants, recent work has shown that within-population variation in resistance can also affect the transmission of foreign spillover pathogens if that resistance is general. However, most hosts also possess specific resistance mechanisms that provide strong defenses against coevolved endemic pathogens. Here we use a modeling approach to ask how antagonistic coevolution between hosts and their endemic pathogen at the specific resistance locus can affect the frequency of general resistance, and therefore a host's vulnerability to foreign pathogens. We develop a two-locus model with variable recombination that incorporates both general (resistance to all pathogens) and specific (resistance to endemic pathogens only). We find that introducing coevolution into our model greatly expands the regions where general resistance can evolve, decreasing the risk of foreign pathogen invasion. Furthermore, coevolution greatly expands which conditions maintain polymorphisms at both resistance loci, thereby driving greater genetic diversity within host populations. This genetic diversity often leads to positive correlations between host resistance to foreign and endemic pathogens, similar to those observed in natural populations. However, if resistance loci become linked, the resistance correlations can shift to negative. If we include a third, linkage modifying locus into our model, we find that selection often favors complete linkage. Our model demonstrates how coevolutionary dynamics with an endemic pathogen can mold the resistance structure of host populations in ways that affect its susceptibility to foreign pathogen spillovers, and that the nature of these outcomes depends on resistance costs, as well as the degree of linkage between resistance genes.

Multimodal pathogen transmission as a limiting factor in host distribution.

Theoretical models suggest that infectious diseases could play a substantial role in determining the spatial extent of host species, but few studies have collected the empirical data required to test this hypothesis. Pathogens that sterilize their hosts or spread through frequency-dependent transmission could have especially strong effects on the limits of species' distributions because diseased hosts that are sterilized but not killed may continue to produce infectious stages and frequency-dependent transmission mechanisms are effective even at very low population densities. We collected spatial pathogen prevalence data and population abundance data for alpine carnations infected by the sterilizing pathogen Microbotryum dianthorum, a parasite that is spread through both frequency-dependent (vector-borne) and density-dependent (aerial spore transmission) mechanisms. Our 13-year study reveals rapid declines in population abundance without a compensatory decrease in pathogen prevalence. We apply a stochastic, spatial model of parasite spread that accommodates spatial habitat heterogeneity to investigate how the population dynamics depend on multimodal (frequency-dependent and density-dependent) transmission. We found that the observed rate of population decline could plausibly be explained by multimodal transmission, but is unlikely to be explained by either frequency-dependent or density-dependent mechanisms alone. Multimodal pathogen transmission rates high enough to explain the observed decline predicted that eventual local extinction of the host species is highly likely. Our results add to a growing body of literature showing how multimodal transmission can constrain species distributions in nature.

Quantitative disease resistance in wild Silene vulgaris to its endemic pathogen Microbotryum silenes-inflatae.

The evolution of disease resistances is an expected feature of plant-pathogen systems, but whether the genetics of this trait most often produces qualitative or quantitative phenotypic variation is a significant gap in our understanding of natural populations. These two forms of resistance variation are often associated with differences in number of underlying loci, the specificities of host-pathogen coevolution, as well as contrasting mechanisms of preventing or slowing the infection process. Anther-smut disease is a commonly studied model for disease of wild species, where infection has severe fitness impacts, and prior studies have suggested resistance variation in several host species. However, because the outcome of exposing the individual host to this pathogen is binary (healthy or diseased), resistance has been previously measured at the family level, as the proportion of siblings that become diseased. This leaves uncertain whether among-family variation reflects contrasting ratios of segregating discrete phenotypes or continuous trait variation among individuals. In the host Silene vulgaris, plants were replicated by vegetative propagation in order to quantify the infection rates of the individual genotype with the endemic anther-smut pathogen, Microbotryum silenes-inflatae. The variance among field-collected families for disease resistance was significant, while there was unimodal continuous variation in resistance among genotypes. Using crosses between genotypes within ranked resistance quartiles, the offspring infection rate was predicted by the parental resistance values. While the potential remains in this system for resistance genes having major effects, as there were suggestions of such qualitative resistance in a prior study, here the quantitative disease resistance to the endemic anther-smut pathogen is indicated for S. vulgaris. The variation in natural populations and strong heritability of the trait, combined with severe fitness consequences of anther-smut disease, suggests that resistance in these host populations is highly capable of responding to disease-induced selection.

Molecular virology: was the 1918 flu avian in origin?

Taubenberger et al. claim that the 1918 influenza virus was derived from an avian source and adapted to humans shortly before the pandemic. However, we do not believe that this conclusion, which has been widely disseminated in the popular press and in scientific journals, is supported by their phylogenetic evidence.

Can disease resistance evolve independently at different ages? Genetic variation in age-dependent resistance to disease in three wild plant species.

Juveniles are typically less resistant (more susceptible) to infectious disease than adults, and this difference in susceptibility can help fuel the spread of pathogens in age-structured populations. However, evolutionary explanations for this variation in resistance across age remain to be tested.One hypothesis is that natural selection has optimized resistance to peak at ages where disease exposure is greatest. A central assumption of this hypothesis is that hosts have the capacity to evolve resistance independently at different ages. This would mean that host populations have (a) standing genetic variation in resistance at both juvenile and adult stages, and (b) that this variation is not strongly correlated between age classes so that selection acting at one age does not produce a correlated response at the other age.Here we evaluated the capacity of three wild plant species (Silene latifolia, S. vulgaris and Dianthus pavonius) to evolve resistance to their anther-smut pathogens (Microbotryum fungi), independently at different ages. The pathogen is pollinator transmitted, and thus exposure risk is considered to be highest at the adult flowering stage.Within each species we grew families to different ages, inoculated individuals with anther smut, and evaluated the effects of age, family and their interaction on infection.In two of the plant species, S. latifolia and D. pavonius, resistance to smut at the juvenile stage was not correlated with resistance to smut at the adult stage. In all three species, we show there are significant age × family interaction effects, indicating that age specificity of resistance varies among the plant families. Synthesis. These results indicate that different mechanisms likely underlie resistance at juvenile and adult stages and support the hypothesis that resistance can evolve independently in response to differing selection pressures as hosts age. Taken together our results provide new insight into the structure of genetic variation in age-dependent resistance in three well-studied wild host-pathogen systems.