Antigenic waves of virus-immune coevolution.

The evolution of many microbes and pathogens, including circulating viruses such as seasonal influenza, is driven by immune pressure from the host population. In turn, the immune systems of infected populations get updated, chasing viruses even farther away. Quantitatively understanding how these dynamics result in observed patterns of rapid pathogen and immune adaptation is instrumental to epidemiological and evolutionary forecasting. Here we present a mathematical theory of coevolution between immune systems and viruses in a finite-dimensional antigenic space, which describes the cross-reactivity of viral strains and immune systems primed by previous infections. We show the emergence of an antigenic wave that is pushed forward and canalized by cross-reactivity. We obtain analytical results for shape, speed, and angular diffusion of the wave. In particular, we show that viral-immune coevolution generates an emergent timescale, the persistence time of the wave's direction in antigenic space, which can be much longer than the coalescence time of the viral population. We compare these dynamics to the observed antigenic turnover of influenza strains, and we discuss how the dimensionality of antigenic space impacts the predictability of the evolutionary dynamics. Our results provide a concrete and tractable framework to describe pathogen-host coevolution.

Strong host phylogenetic and ecological effects on host competency for avian influenza in Australian wild birds.

Host susceptibility to parasites is mediated by intrinsic and external factors such as genetics, ecology, age and season. While waterfowl are considered central to the reservoir community for low pathogenic avian influenza A viruses (LPAIV), the role of host phylogeny has received limited formal attention. Herein, we analysed 12 339 oropharyngeal and cloacal swabs and 10 826 serum samples collected over 11 years from wild birds in Australia. As well as describing age and species-level differences in prevalence and seroprevalence, we reveal that host phylogeny is a key driver in host range. Seasonality effects appear less pronounced than in the Northern Hemisphere, while annual variations are potentially linked to El Niño-Southern Oscillation. Our study provides a uniquely detailed insight into the evolutionary ecology of LPAIV in its avian reservoir community, defining distinctive processes on the continent of Australia and expanding our understanding of LPAIV globally.

Variability in environmental persistence but not per capita transmission rates of the amphibian chytrid fungus leads to differences in host infection prevalence.

Heterogeneities in infections among host populations may arise through differences in environmental conditions through two mechanisms. First, environmental conditions may alter host exposure to pathogens via effects on survival. Second, environmental conditions may alter host susceptibility, making infection more or less likely if contact between a host and pathogen occurs. Further, host susceptibility might be altered through acquired resistance, which hosts can develop, in some systems, through exposure to dead or decaying pathogens and their metabolites. Environmental conditions may alter the rates of pathogen decomposition, influencing the likelihood of hosts developing acquired resistance. The present study primarily tests how environmental context influences the relative contributions of pathogen survival and per capita transmission on host infection prevalence using the amphibian chytrid fungus (Batrachochytrium dendrobatidis; Bd) as a model system. Secondarily, we evaluate how environmental context influences the decomposition of Bd because previous studies have shown that dead Bd and its metabolites can illicit acquired resistance in hosts. We conducted Bd survival and infection experiments and then fit models to discern how Bd mortality, decomposition and per capita transmission rates vary among water sources [e.g. artificial spring water (ASW) or water from three ponds]. We found that infection prevalence differed among water sources, which was driven by differences in mortality rates of Bd, rather than differences in per capita transmission rates. Bd mortality rates varied among pond water treatments and were lower in ASW compared to pond water. These results suggest that variation in Bd infection dynamics could be a function of environmental factors in waterbodies that result in differences in exposure of hosts to live Bd. In contrast to the persistence of live Bd, we found that the rates of decomposition of dead Bd did not vary among water sources, which may suggest that exposure of hosts to dead Bd or its metabolites might not commonly vary among nearby sites. Ultimately, a mechanistic understanding of the environmental dependence of free-living pathogens could lead to a deeper understanding of the patterns of outbreak heterogeneity, which could inform surveillance and management strategies.

Separate seasons of infection and reproduction can lead to multi-year population cycles.

Many host-pathogen systems are characterized by a temporal order of disease transmission and host reproduction. For example, this can be due to pathogens infecting certain life cycle stages of insect hosts; transmission occurring during the aggregation of migratory birds; or plant diseases spreading between planting seasons. We develop a simple discrete-time epidemic model with density-dependent transmission and disease affecting host fecundity and survival. The model shows sustained multi-annual cycles in host population abundance and disease prevalence, both in the presence and absence of density dependence in host reproduction, for large horizontal transmissibility, imperfect vertical transmission, high virulence, and high reproductive capability. The multi-annual cycles emerge as invariant curves in a Neimark-Sacker bifurcation. They are caused by a carry-over effect, because the reproductive fitness of an individual can be reduced by virulent effects due to infection in an earlier season. As the infection process is density-dependent but shows an effect only in a later season, this produces delayed density dependence typical for second-order oscillations. The temporal separation between the infection and reproduction season is crucial in driving the cycles; if these processes occur simultaneously as in differential equation models, there are no sustained oscillations. Our model highlights the destabilizing effects of inter-seasonal feedbacks and is one of the simplest epidemic models that can generate population cycles.

American foulbrood in a honeybee colony: spore-symptom relationship and feedbacks.

BACKGROUND: The most severe bacterial disease of honeybees is American foulbrood (AFB). The epidemiology of AFB is driven by the extreme spore resilience, the difficulty of bees to remove these spores, and the considerable incidence of undetected spore-producing colonies. The honeybee collective defence mechanisms and their feedback on colony development, which involves a division of labour at multiple levels of colony organization, are difficult to model. To better predict disease outbreaks we need to understand the feedback between colony development and disease progression within the colony. We therefore developed Bayesian models with data from forty AFB-diseased colonies monitored over an entire foraging season to (i) investigate the relationship between spore production and symptoms, (ii) disentangle the feedback loops between AFB epidemiology and natural colony development, and (iii) discuss whether larger insect societies promote or limit within-colony disease transmission. RESULTS: Rather than identifying a fixed spore count threshold for clinical symptoms, we estimated the probabilities around the relationship between spore counts and symptoms, taking into account modulators such as brood amount/number of bees and time post infection. We identified a decrease over time in the bees-to-brood ratio related to disease development, which should ultimately induce colony collapse. Lastly, two contrasting theories predict that larger colonies could promote either higher (classical epidemiological SIR-model) or lower (increasing spatial nest segregation and more effective pathogen removal) disease prevalence. CONCLUSIONS: AFB followed the predictions of the SIR-model, partly because disease prevalence and brood removal are decoupled, with worker bees acting more as disease vectors, infecting new brood, than as agents of social immunity, by removing infected brood. We therefore established a direct link between disease prevalence and social group size for a eusocial insect. We furthermore provide a probabilistic description of the relationship between AFB spore counts and symptoms, and how disease development and colony strength over a season modulate this relationship. These results help to better understand disease development within honeybee colonies, provide important estimates for further epidemiological modelling, and gained important insights into the optimal sampling strategy for practical beekeeping and honeybee research.

Honeybee-Specific Lactic Acid Bacterium Supplements Have No Effect on American Foulbrood-Infected Honeybee Colonies.

Paenibacillus larvae, the causative agent of American foulbrood (AFB), is the primary bacterial pathogen affecting honeybees and beekeeping. The main methods for controlling AFB are incineration of diseased colonies or prophylactic antibiotic treatment (e.g., with tylosin), neither of which is fully satisfactory. The search for superior means for controlling AFB has led to an increased interest in the natural relationships between the honeybee-pathogenic and mutualistic microorganisms and, in particular, the antagonistic effects of honeybee-specific lactic acid bacteria (hbs-LAB) against P. larvae These effects have been demonstrated only on individual larvae in controlled laboratory bioassays. Here we investigated whether supplemental administration of hbs-LAB had a similar beneficial effect on P. larvae infection at colony level. We compared experimentally AFB-infected colonies treated with hbs-LAB supplements to untreated and tylosin-treated colonies and recorded AFB symptoms, bacterial spore levels, and two measures of colony health. To account for the complexity of a bee colony, we focused on (Bayesian) probabilities and magnitudes of effect sizes. Tylosin reduced AFB disease symptoms but also had a negative effect on colony strength. The tylosin treatment did not, however, affect P. larvae spore levels and might therefore "mask" the potential for disease. hbs-LAB tended to reduce brood size in the short term but was unlikely to affect AFB symptoms or spores. These results do not contradict demonstrated antagonistic effects of hbs-LAB against P. larvae at the individual bee level but rather suggest that supplementary administration of hbs-LAB may not be the most effective way to harness these beneficial effects at the colony level.IMPORTANCE The previously demonstrated antagonistic effects of honeybee-derived bacterial microbiota on the infectivity and pathogenicity of P. larvae in laboratory bioassays have identified a possible new approach to AFB control. However, honeybee colonies are complex superorganisms where social immune defenses play a major role in resistance against disease at the colony level. Few studies have investigated the effect of beneficial microorganisms on bee diseases at the colony level. Effects observed at the individual bee level do not necessarily translate into similar effects at the colony level. This study partially fills this gap by showing that, unlike at the individual level, hbs-LAB supplements did not affect AFB symptoms at the colony level. The inference is that the mechanisms regulating the honeybee microbial dynamics within a colony are too strong to manipulate positively through supplemental feeding of live hbs-LAB and that new potential remedies identified through laboratory research have to be tested thoroughly in situ, in colonies.

Social Immunity: Emergence and Evolution of Colony-Level Disease Protection.

Social insect colonies have evolved many collectively performed adaptations that reduce the impact of infectious disease and that are expected to maximize their fitness. This colony-level protection is termed social immunity, and it enhances the health and survival of the colony. In this review, we address how social immunity emerges from its mechanistic components to produce colony-level disease avoidance, resistance, and tolerance. To understand the evolutionary causes and consequences of social immunity, we highlight the need for studies that evaluate the effects of social immunity on colony fitness. We discuss the roles that host life history and ecology have on predicted eco-evolutionary dynamics, which differ among the social insect lineages. Throughout the review, we highlight current gaps in our knowledge and promising avenues for future research, which we hope will bring us closer to an integrated understanding of socio-eco-evo-immunology.

Host-pathogen metapopulation dynamics suggest high elevation refugia for boreal toads.

Emerging infectious diseases are an increasingly common threat to wildlife. Chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), is an emerging infectious disease that has been linked to amphibian declines around the world. Few studies exist that explore amphibian-Bd dynamics at the landscape scale, limiting our ability to identify which factors are associated with variation in population susceptibility and to develop effective in situ disease management. Declines of boreal toads (Anaxyrus boreas boreas) in the southern Rocky Mountains are largely attributed to chytridiomycosis but variation exists in local extinction of boreal toads across this metapopulation. Using a large-scale historic data set, we explored several potential factors influencing disease dynamics in the boreal toad-Bd system: geographic isolation of populations, amphibian community richness, elevational differences, and habitat permanence. We found evidence that boreal toad extinction risk was lowest at high elevations where temperatures may be suboptimal for Bd growth and where small boreal toad populations may be below the threshold needed for efficient pathogen transmission. In addition, boreal toads were more likely to recolonize high elevation sites after local extinction, again suggesting that high elevations may provide refuge from disease for boreal toads. We illustrate a modeling framework that will be useful to natural resource managers striving to make decisions in amphibian-Bd systems. Our data suggest that in the southern Rocky Mountains high elevation sites should be prioritized for conservation initiatives like reintroductions.

Migratory animals feel the cost of getting sick: A meta-analysis across species.

Migratory animals are widely assumed to play an important role in the long-distance dispersal of parasites, and are frequently implicated in the global spread of zoonotic pathogens such as avian influenzas in birds and Ebola viruses in bats. However, infection imposes physiological and behavioural constraints on hosts that may act to curtail parasite dispersal via changes to migratory timing ("migratory separation") and survival ("migratory culling"). There remains little consensus regarding the frequency and extent to which migratory separation and migratory culling may operate, despite a growing recognition of the importance of these mechanisms in regulating transmission dynamics in migratory animals. We quantitatively reviewed 85 observations extracted from 41 studies to examine how both infection status and infection intensity are related to changes in body stores, refuelling rates, movement capacity, phenology and survival in migratory hosts across taxa. Overall, host infection status was weakly associated with reduced body stores, delayed migration and lower survival, and more strongly associated with reduced movement. Infection intensity was not associated with changes to host body stores, but was associated with moderate negative effects on movement, phenology and survival. In conclusion, we found evidence for negative effects of infection on host phenology and survival, but the effects were relatively small. This may have implications for the extent to which migratory separation and migratory culling act to limit parasite dispersal in migratory systems. We propose a number of recommendations for future research that will further advance our understanding of how migratory separation and migratory culling may shape host-parasite dynamics along migratory routes globally.

The Evolution of Innate Immune Genes: Purifying and Balancing Selection on ß-Defensins in Waterfowl.

In disease dynamics, high immune gene diversity can confer a selective advantage to hosts in the face of a rapidly evolving and diverse pathogen fauna. This is supported empirically for genes involved in pathogen recognition and signalling. In contrast, effector genes involved in pathogen clearance may be more constrained. ß-Defensins are innate immune effector genes; their main mode of action is via disruption of microbial membranes. Here, five ß-defensin genes were characterized in mallards (Anas platyrhynchos) and other waterfowl; key reservoir species for many zoonotic diseases. All five genes showed remarkably low diversity at the individual-, population-, and species-level. Furthermore, there was widespread sharing of identical alleles across species divides. Thus, specific ß-defensin alleles were maintained not only spatially but also over long temporal scales, with many amino acid residues being fixed across all species investigated. Purifying selection to maintain individual, highly efficacious alleles was the primary evolutionary driver of these genes in waterfowl. However, we also found evidence for balancing selection acting on the most recently duplicated ß-defensin gene (AvBD3b). For this gene, we found that amino acid replacements were more likely to be radical changes, suggesting that duplication of ß-defensin genes allows exploration of wider functional space. Structural conservation to maintain function appears to be crucial for avian ß-defensin effector molecules, resulting in low tolerance for new allelic variants. This contrasts with other types of innate immune genes, such as receptor and signalling molecules, where balancing selection to maintain allelic diversity has been shown to be a strong evolutionary force.

Historical amphibian declines and extinctions in Brazil linked to chytridiomycosis.

The recent increase in emerging fungal diseases is causing unprecedented threats to biodiversity. The origin of spread of the frog-killing fungus Batrachochytrium dendrobatidis (Bd) is a matter of continued debate. To date, the historical amphibian declines in Brazil could not be attributed to chytridiomycosis; the high diversity of hosts coupled with the presence of several Bd lineages predating the reported declines raised the hypothesis that a hypervirulent Bd genotype spread from Brazil to other continents causing the recent global amphibian crisis. We tested for a spatio-temporal overlap between Bd and areas of historical amphibian population declines and extinctions in Brazil. A spatio-temporal convergence between Bd and declines would support the hypothesis that Brazilian amphibians were not adapted to Bd prior to the reported declines, thus weakening the hypothesis that Brazil was the global origin of Bd emergence. Alternatively, a lack of spatio-temporal association between Bd and frog declines would indicate an evolution of host resistance in Brazilian frogs predating Bd's global emergence, further supporting Brazil as the potential origin of the Bd panzootic. Here, we Bd-screened over 30 000 museum-preserved tadpoles collected in Brazil between 1930 and 2015 and overlaid spatio-temporal Bd data with areas of historical amphibian declines. We detected an increase in the proportion of Bd-infected tadpoles during the peak of amphibian declines (1979-1987). We also found that clusters of Bd-positive samples spatio-temporally overlapped with most records of amphibian declines in Brazil's Atlantic Forest. Our findings indicate that Brazil is post epizootic for chytridiomycosis and provide another piece to the puzzle to explain the origin of Bd globally.

Temperature variation, bacterial diversity and fungal infection dynamics in the amphibian skin.

Host-associated bacterial communities on the skin act as the first line of defence against invading pathogens. Yet, for most natural systems, we lack a clear understanding of how temperature variability affects structure and composition of skin bacterial communities and, in turn, promotes or limits the colonization of opportunistic pathogens. Here, we examine how natural temperature fluctuations might be related to changes in skin bacterial diversity over time in three amphibian populations infected by the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Our focal host species (Eleutherodactylus coqui) is a direct-developing frog that has suffered declines at some populations in the last 20 years, while others have not experienced any changes. We quantified skin bacterial alpha- and beta-diversity at four sampling time points, a period encompassing two seasons and ample variation in natural infections and environmental conditions. Despite the different patterns of infection across populations, we detected an overall increase in bacterial diversity through time, characterized by the replacement of bacterial operational taxonomic units (OTUs). Increased frog body temperatures possibly allowed the colonization of bacteria as well as the recruitment of a subset of indicator OTUs, which could have promoted the observed changes in diversity patterns. Our results suggest that natural environmental fluctuations might be involved in creating opportunities for bacterial replacement, potentially attenuating pathogen transmission and thus contributing to host persistence in E. coqui populations.

Injecting epidemiology into population viability analysis: avian cholera transmission dynamics at an arctic seabird colony.

Infectious diseases have the potential to spread rapidly and cause high mortality within populations of immunologically naïve hosts. The recent appearance of avian cholera, a highly virulent disease of birds caused by the bacterium Pasteurella multocida, at remote Arctic seabird colonies is an emerging conservation concern. Determining disease risk to population viability requires a quantitative understanding of transmission potential and the factors that regulate epidemic persistence. Estimates of the basic (R0 ) and real-time (Rt ) reproductive number are critical in this regard - enumerating the number of secondary infections caused by each primary infection in a newly invaded host population and the decline in transmission rate as susceptible individuals are removed via mortality or immunized recovery. Here, we use data collected at a closely monitored common eider (Somateria mollissima) breeding colony located in the Canadian Arctic to examine transmission and host population dynamics. Specifically, we infer epidemic curves from daily mortality observations and use a likelihood-based procedure to estimate changes in the reproductive number over a series of annual outbreaks. These data are interpreted in relation to concurrent changes in host numbers to assess local extinction risk. Consistent with expectations for a novel pathogen invasion, case incidence increased exponentially during the initial wave of exposure (R0  = 2·5; generation time = 6·5 days ± 1·1 SD). Disease conditions gradually abated, but only after several years of smouldering infection (Rt  ≈ 1). In total, 6194 eider deaths were recorded during outbreaks spanning eight consecutive breeding seasons. Breeding pair abundance declined by 56% from the pre-outbreak peak; however, a robust population of >4000 pairs remained intact upon epidemic fade-out. Overall, outbreak patterns were consistent with herd immunity acting as a mitigating factor governing in the extent and duration of mortality. Disease mortality is frequently modelled as a form of stochastic catastrophe in wildlife population assessments, whereas our approach gives shape to the functional response between transmission and host population dynamics. We conclude that increased emphasis on integrating epidemiological and population processes is essential to predicting the conservation impact of emerging infectious diseases in wildlife.

Resolving the roles of immunity, pathogenesis, and immigration for rabies persistence in vampire bats.

Bats are important reservoirs for emerging infectious diseases, yet the mechanisms that allow highly virulent pathogens to persist within bat populations remain obscure. In Latin America, vampire-bat-transmitted rabies virus represents a key example of how such uncertainty can impede efforts to prevent cross-species transmission. Despite decades of agricultural and human health losses, control efforts have had limited success. To establish persistence mechanisms of vampire-bat-transmitted rabies virus in Latin America, we use data from a spatially replicated, longitudinal field study of vampire bats in Peru to parameterize a series of mechanistic transmission models. We find that single-colony persistence cannot occur. Instead, dispersal of bats between colonies, combined with a high frequency of immunizing nonlethal infections, is necessary to maintain rabies virus at levels consistent with field observations. Simulations show that the strong spatial component to transmission dynamics could explain the failure of bat culls to eliminate rabies and suggests that geographic coordination of control efforts might reduce transmission to humans and domestic animals. These findings offer spatial dynamics as a mechanism for rabies persistence in bats that might be important for the understanding and control of other bat-borne pathogens.

Infectious disease transmission and behavioural allometry in wild mammals.

Animals' social and movement behaviours can impact the transmission dynamics of infectious diseases, especially for pathogens transmitted through close contact between hosts or through contact with infectious stages in the environment. Estimating pathogen transmission rates and R0 from natural systems can be challenging. Because host behavioural traits that underlie the transmission process vary predictably with body size, one of the best-studied traits among animals, body size might therefore also predict variation in parasite transmission dynamics. Here, we examine how two host behaviours, social group living and the intensity of habitat use, scale allometrically using comparative data from wild primate, carnivore and ungulate species. We use these empirical relationships to parameterize classical compartment models for infectious micro- and macroparasitic diseases, and examine how the risk of pathogen invasion changes as a function of host behaviour and body size. We then test model predictions using comparative data on parasite prevalence and richness from wild mammals. We report a general pattern suggesting that smaller-bodied mammal species utilizing home ranges more intensively experience greater risk for invasion by environmentally transmitted macroparasites. Conversely, larger-bodied hosts exhibiting a high degree of social group living could be more readily invaded by directly transmitted microparasites. These trends were supported through comparison of micro- and macroparasite species richness across a large number of carnivore, primate and ungulate species, but empirical data on carnivore macroparasite prevalence showed mixed results. Collectively, our study demonstrates that combining host behavioural traits with dynamical models of infectious disease scaled against host body size can generate testable predictions for variation in parasite risk across species; a similar approach might be useful in future work focused on predicting parasite distributions in local host communities.

Resource asynchrony and landscape homogenization as drivers of virulence evolution: The case of a directly transmitted disease in a social host.

Throughout the last decades, the emergence of zoonotic diseases and the frequency of disease outbreaks have increased substantially, fuelled by habitat encroachment and vectors overlapping with more hosts due to global change. The virulence of pathogens is one key trait for successful invasion. In order to understand how global change drivers such as habitat homogenization and climate change drive pathogen virulence evolution, we adapted an established individual-based model of host-pathogen dynamics. Our model simulates a population of social hosts affected by a directly transmitted evolving pathogen in a dynamic landscape. Pathogen virulence evolution results in multiple strains in the model that differ in their transmission capability and lethality. We represent the effects of global change by simulating environmental changes both in time (resource asynchrony) and space (homogenization). We found an increase in pathogenic virulence and a shift in strain dominance with increasing landscape homogenization. Our model further indicated that lower virulence is dominant in fragmented landscapes, although pulses of highly virulent strains emerged under resource asynchrony. While all landscape scenarios favoured co-occurrence of low- and high-virulent strains, the high-virulence strains capitalized on the possibility for transmission when host density increased and were likely to become dominant. With asynchrony likely to occur more often due to global change, our model showed that a subsequent evolution towards lower virulence could lead to some diseases becoming endemic in their host populations.

Chronic wasting disease alters the movement behavior and habitat use of mule deer during clinical stages of infection.

Integrating host movement and pathogen data is a central issue in wildlife disease ecology that will allow for a better understanding of disease transmission. We examined how adult female mule deer (Odocoileus hemionus) responded behaviorally to infection with chronic wasting disease (CWD). We compared movement and habitat use of CWD-infected deer (n = 18) to those that succumbed to starvation (and were CWD-negative by ELISA and IHC; n = 8) and others in which CWD was not detected (n = 111, including animals that survived the duration of the study) using GPS collar data from two distinct populations collared in central Wyoming, USA during 2018-2022. CWD and predation were the leading causes of mortality during our study (32/91 deaths attributed to CWD and 27/91 deaths attributed to predation). Deer infected with CWD moved slower and used lower elevation areas closer to rivers in the months preceding death compared with uninfected deer that did not succumb to starvation. Although CWD-infected deer and those that died of starvation moved at similar speeds during the final months of life, CWD-infected deer used areas closer to streams with less herbaceous biomass than starved deer. These behavioral differences may allow for the development of predictive models of disease status from movement data, which will be useful to supplement field and laboratory diagnostics or when mortalities cannot be quickly retrieved to assess cause-specific mortality. Furthermore, identifying individuals who are sick before predation events could help to assess the extent to which disease mortality is compensatory with predation. Finally, infected animals began to slow down around 4 months prior to death from CWD. Our approach for detecting the timing of infection-induced shifts in movement behavior may be useful in application to other disease systems to better understand the response of wildlife to infectious disease.

Nonparallelism in MHCIIß diversity accompanies nonparallelism in pathogen infection of lake whitefish (Coregonus clupeaformis) species pairs as revealed by next-generation sequencing.

Major histocompatibility (MHC) immune system genes may evolve in response to pathogens in the environment. Because they also may affect mate choice, they are candidates for having great importance in ecological speciation. Here, we use next-generation sequencing to test the general hypothesis of parallelism in patterns of MHCIIß diversity and bacterial infections among five dwarf and normal whitefish sympatric pairs. A second objective was to assess the functional relationships between specific MHCIIß alleles and pathogens in natural conditions. Each individual had between one and four alleles, indicating two paralogous loci. In Cliff Lake, the dwarf ecotype was monomorphic for the most common allele. In Webster Lake, the skew in the allelic distribution was towards the same allele but in the normal ecotype, underscoring the nonparallel divergence among lakes. Our signal of balancing selection matched putative peptide binding region residues in some cases, but not in others, supporting other recent findings of substantial functional differences in fish MHCIIß compared with mammals. Individuals with fewer alleles were less likely to be infected; thus, we found no evidence for the heterozygote advantage hypothesis. MHCIIß alleles and pathogenic bacteria formed distinct clusters in multivariate analyses, and clusters of certain alleles were associated with clusters of pathogens, or sometimes the absence of pathogens, indicating functional relationships at the individual level. Given that patterns of MHCIIß and bacteria were nonparallel among dwarf and normal whitefish pairs, we conclude that pathogens driving MHCIIß evolution did not play a direct role in their parallel phenotypic evolution.

Assessing spatial distribution, genetic variants, and virulence of pathogen Mycoplasma agassizii in threatened Mojave desert tortoises.

Mojave desert tortoises (Gopherus agassizii), a threatened species under the US Endangered Species Act, are long-lived reptiles that experience a chronic respiratory disease. The virulence of primary etiologic agent, Mycoplasma agassizii, remains poorly understood, but it exhibits temporal and geographic variability in causing disease outbreaks in host tortoises. Multiple attempts to culture and characterize the diversity of M. agassizii have had minimal success, even though this opportunistic pathogen chronically persists in nearly every population of Mojave desert tortoises. The current geographic range and the molecular mechanisms of virulence of the type-strain, PS6T, are unknown, and the bacterium is thought to have low-to-moderate virulence. We designed a quantitative polymerase chain reaction (qPCR) targeting three putative virulence genes annotated on the PS6T genome as exo-α-sialidases, enzymes which facilitate growth in many bacterial pathogens. We tested 140 M. agassizii-positive DNA samples collected from 2010 to 2012 across the range of Mojave desert tortoises. We found evidence of multiple-strain infections within hosts. We also found the prevalence of these sialidase-encoding genes to be highest in tortoise populations surrounding southern Nevada, the area from which PS6T was originally isolated. We found a general pattern of loss or reduced presence of sialidase among strains, even within a single host. However, in samples that were positive for any of the putative sialidase genes, one particular gene (528), was positively associated with bacterial loads of M. agassizii and may act as a growth factor for the bacterium. Our results suggest three evolutionary patterns: (1) high levels of variation, possibly due to neutral changes and chronic persistence, (2) a trade-off between moderate virulence and transmission, and (3) selection against virulence in environmental conditions known to be physiologically stressful to the host. Our approach of quantifying genetic variation via qPCR represents a useful model of studying host-pathogen dynamics.

Movement can mediate temporal mismatches between resource availability and biological events in host-pathogen interactions.

Global change is shifting the timing of biological events, leading to temporal mismatches between biological events and resource availability. These temporal mismatches can threaten species' populations. Importantly, temporal mismatches not only exert strong pressures on the population dynamics of the focal species, but can also lead to substantial changes in pairwise species interactions such as host-pathogen systems. We adapted an established individual-based model of host-pathogen dynamics. The model describes a viral agent in a social host, while accounting for the host's explicit movement decisions. We aimed to investigate how temporal mismatches between seasonal resource availability and host life-history events affect host-pathogen coexistence, that is, disease persistence. Seasonal resource fluctuations only increased coexistence probability when in synchrony with the hosts' biological events. However, a temporal mismatch reduced host-pathogen coexistence, but only marginally. In tandem with an increasing temporal mismatch, our model showed a shift in the spatial distribution of infected hosts. It shifted from an even distribution under synchronous conditions toward the formation of disease hotspots, when host life history and resource availability mismatched completely. The spatial restriction of infected hosts to small hotspots in the landscape initially suggested a lower coexistence probability due to the critical loss of susceptible host individuals within those hotspots. However, the surrounding landscape facilitated demographic rescue through habitat-dependent movement. Our work demonstrates that the negative effects of temporal mismatches between host resource availability and host life history on host-pathogen coexistence can be reduced through the formation of temporary disease hotspots and host movement decisions, with implications for disease management under disturbances and global change.