Dispersal evolution and eco-evolutionary dynamics in antagonistic species interactions.

Dispersal evolution modifies diverse spatial processes, such as range expansions or biological invasions of single species, but we are currently lacking a realistic vision for metacommunities. Focusing on antagonistic species interactions, we review existing theory of dispersal evolution between natural enemies, and explain how this might be relevant for classic themes in host-parasite evolutionary ecology, namely virulence evolution or local adaptation. Specifically, we highlight the importance of considering the simultaneous (co)evolution of dispersal and interaction traits. Linking such multi-trait evolution with reciprocal demographic and epidemiological feedbacks might change basic predictions about coevolutionary processes and spatial dynamics of interacting species. Future challenges concern the integration of system-specific disease ecology or spatial modifiers, such as spatial network structure or environmental heterogeneity.

Predicting evolution in experimental range expansions of an aquatic model system.

Predicting range expansion dynamics is an important goal of both fundamental and applied research in conservation and global change biology. However, this is challenging if ecological and evolutionary processes occur on the same time scale. Using the freshwater ciliate Paramecium caudatum, we combined experimental evolution and mathematical modeling to assess the predictability of evolutionary change during range expansions. In the experiment, we followed ecological dynamics and trait evolution in independently replicated microcosm populations in range core and front treatments, where episodes of natural dispersal alternated with periods of population growth. These eco-evolutionary conditions were recreated in a predictive mathematical model, parametrized with dispersal and growth data of the 20 founder strains in the experiment. We found that short-term evolution was driven by selection for increased dispersal in the front treatment and general selection for higher growth rates in all treatments. There was a good quantitative match between predicted and observed trait changes. Phenotypic divergence was further mirrored by genetic divergence between range core and front treatments. In each treatment, we found the repeated fixation of the same cytochrome c oxidase I (COI) marker genotype, carried by strains that also were the most likely winners in our model. Long-term evolution in the experimental range front lines resulted in the emergence of a dispersal syndrome, namely a competition-colonization trade-off. Altogether, both model and experiment highlight the potential importance of dispersal evolution as a driver of range expansions. Thus, evolution at range fronts may follow predictable trajectories, at least for simple scenarios, and predicting these dynamics may be possible from knowledge of few key parameters.

Travelling with a parasite: the evolution of resistance and dispersal syndromes during experimental range expansion.

Rapid evolutionary change during range expansions can lead to diverging range core and front populations, with the emergence of dispersal syndromes (coupled responses in dispersal and life-history traits). Besides intraspecific effects, range expansions may be impacted by interspecific interactions such as parasitism. Yet, despite the potentially large impact of parasites imposing additional selective pressures on the host, their role on range expansions remains largely unexplored. Using microcosm populations of the ciliate Paramecium caudatum and its bacterial parasite Holospora undulata, we studied experimental range expansions under parasite presence or absence. We found that the interaction of range expansion and parasite treatments affected the evolution of host dispersal syndromes. Namely, front populations showed different associations of population growth parameters and swimming behaviours than core populations, indicating divergent evolution. Parasitism reshaped trait associations, with hosts evolved in the presence of the parasite exhibiting overall increased resistance and reduced dispersal. Nonetheless, when comparing infected range core and front populations, we found a positive association, suggesting joint evolution of resistance and dispersal at the front. We conclude that host-parasite interactions during range expansions can change evolutionary trajectories; this in turn may feedback on the ecological dynamics of the range expansion and parasite epidemics.

Dispersal syndromes in challenging environments: A cross-species experiment.

Dispersal is a central biological process tightly integrated into life-histories, morphology, physiology and behaviour. Such associations, or syndromes, are anticipated to impact the eco-evolutionary dynamics of spatially structured populations, and cascade into ecosystem processes. As for dispersal on its own, these syndromes are likely neither fixed nor random, but conditional on the experienced environment. We experimentally studied how dispersal propensity varies with individuals' phenotype and local environmental harshness using 15 species ranging from protists to vertebrates. We reveal a general phenotypic dispersal syndrome across studied species, with dispersers being larger, more active and having a marked locomotion-oriented morphology and a strengthening of the link between dispersal and some phenotypic traits with environmental harshness. Our proof-of-concept metacommunity model further reveals cascading effects of context-dependent syndromes on the local and regional organisation of functional diversity. Our study opens new avenues to advance our understanding of the functioning of spatially structured populations, communities and ecosystems.

Genetic diversity and connectivity of the Ostreid herpesvirus 1 populations in France: A first attempt to phylogeographic inference for a marine mollusc disease.

The genetic diversity of viral populations is a key driver of the spatial and temporal diffusion of viruses; yet, studying the diversity of whole genomes from natural populations still remains a challenge. Phylodynamic approaches are commonly used for RNA viruses harboring small genomes but have only rarely been applied to DNA viruses with larger genomes. Here, we used the Pacific oyster mortality syndrome (a disease that affects oyster farms around the world) as a model to study the genetic diversity of its causative agent, the Ostreid herpesvirus 1 (OsHV-1) in the three main French oyster-farming areas. Using ultra-deep sequencing on individual moribund oysters and an innovative combination of bioinformatics tools, we de novo assembled twenty-one OsHV-1 new genomes. Combining quantification of major and minor genetic variations, phylogenetic analysis, and ancestral state reconstruction of discrete traits approaches, we assessed the connectivity of OsHV-1 viral populations between the three oyster-farming areas. Our results suggest that the Marennes-Oléron Bay represents the main source of OsHV-1 diversity, from where the virus has dispersed to other farming areas, a scenario consistent with current practices of oyster transfers in France. We demonstrate that phylodynamic approaches can be applied to aquatic DNA viruses to determine how epidemiological, immunological, and evolutionary processes act and potentially interact to shape their diversity patterns.

Parasitism and host dispersal plasticity in an aquatic model system.

Dispersal is a central determinant of spatial dynamics in communities and ecosystems, and various ecological factors can shape the evolution of constitutive and plastic dispersal behaviours. One important driver of dispersal plasticity is the biotic environment. Parasites, for example, influence the internal condition of infected hosts and define external patch quality. Thus, state-dependent dispersal may be determined by infection status and context-dependent dispersal by the abundance of infected hosts in the population. A prerequisite for such dispersal plasticity to evolve is a genetic basis on which natural selection can act. Using interconnected microcosms, we investigated dispersal in experimental populations of the freshwater protist Paramecium caudatum in response to the bacterial parasite Holospora undulata. For a collection of 20 natural host strains, we found substantial variation in constitutive dispersal and to a lesser degree in dispersal plasticity. First, infection tended to increase or decrease dispersal relative to uninfected controls, depending on strain identity, indicative of state-dependent dispersal plasticity. Infection additionally decreased host swimming speed compared to the uninfected counterparts. Second, for certain strains, there was a weak negative association between dispersal and infection prevalence, such that uninfected hosts dispersed less when infection was more frequent in the population, indicating context-dependent dispersal plasticity. Future experiments may test whether the observed differences in dispersal plasticity are sufficiently strong to be picked up by natural selection. The evolution of dispersal plasticity as a strategy to mitigate parasite effects spatially may have important implications for epidemiological dynamics.

An evolutionary trade-off between parasite virulence and dispersal at experimental invasion fronts.

Exploitative parasites are predicted to evolve in highly connected populations or in expanding epidemics. However, many parasites rely on host dispersal to reach new populations, potentially causing conflict between local transmission and global spread. We performed experimental range expansions in interconnected microcosms of the protozoan Paramecium caudatum, allowing natural dispersal of hosts infected with the bacterial parasite Holospora undulata. Parasites from range front treatments facilitated host dispersal and were less virulent, but also invested less in horizontal transmission than parasites from range cores. These differences were consistent with parameter estimates derived from an epidemiological model fitted on population-level time-series data. Our results illustrate how dispersal selection can have profound consequences for the evolution of parasite life history and virulence. Decrypting the eco-evolutionary processes that shape parasite 'dispersal syndromes' may be important for the management of spreading epidemics in changing environments, biological invasions or in other spatial non-equilibrium settings.

Among-Strain Variation in Resistance of Paramecium caudatum to the Endonuclear Parasite Holospora undulata: Geographic and Lineage-Specific Patterns.

Resistance is a key determinant in interactions between hosts and their parasites. Understanding the amount and distribution of variation in this trait between strains can provide insights into (co)evolutionary processes and their potential to shape patterns of diversity in natural populations. Using controlled inoculation in experimental mass cultures, we investigated the quantitative variation in resistance to the bacterial parasite Holospora undulata across a worldwide collection of strains of its ciliate host Paramecium caudatum. We combined the observed variation with available information on the phylogeny and biogeography of the strains. We found substantial variation in resistance among strains, with upper-bound values of broad-sense heritability >0.5 (intraclass correlation coefficients). Strain estimates of resistance were repeatable between laboratories and ranged from total resistance to near-complete susceptibility. Early (1 week post inoculation) measurements provided higher estimates of resistance heritability than did later measurements (2-3 weeks), possibly due to diverging epidemiological dynamics in replicate cultures of the same strains. Genetic distance (based on a neutral marker) was positively correlated with the difference in resistance phenotype between strains (r = 0.45), essentially reflecting differences between highly divergent clades (haplogroups) within the host species. Haplogroup A strains, mostly European, were less resistant to the parasite (49% infection prevalence) than non-European haplogroup B strains (28%). At a smaller geographical scale (within Europe), strains that are geographically closer to the parasite origin (Southern Germany) were more susceptible to infection than those from further away. These patterns are consistent with a picture of local parasite adaptation. Our study demonstrates ample natural variation in resistance on which selection can act and hints at symbiont adaptation producing signatures in geographic and lineage-specific patterns of resistance in this model system.

Phage steering of antibiotic-resistance evolution in the bacterial pathogen, Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVES: Antimicrobial resistance is a growing global concern and has spurred increasing efforts to find alternative therapeutics. Bacteriophage therapy has seen near constant use in Eastern Europe since its discovery over a century ago. One promising approach is to use phages that not only reduce bacterial pathogen loads but also select for phage resistance mechanisms that trade-off with antibiotic resistance-so called 'phage steering'. METHODOLOGY: Recent work has shown that the phage OMKO1 can interact with efflux pumps and in so doing select for both phage resistance and antibiotic sensitivity of the pathogenic bacterium Pseudomonas aeruginosa. We tested the robustness of this approach to three different antibiotics in vitro (tetracycline, erythromycin and ciprofloxacin) and one in vivo (erythromycin). RESULTS: We show that in vitro OMKO1 can reduce antibiotic resistance of P. aeruginosa (Washington PAO1) even in the presence of antibiotics, an effect still detectable after ca.70 bacterial generations in continuous culture with phage. Our in vivo experiment showed that phage both increased the survival times of wax moth larvae (Galleria mellonella) and increased bacterial sensitivity to erythromycin. This increased antibiotic sensitivity occurred both in lines with and without the antibiotic. CONCLUSIONS AND IMPLICATIONS: Our study supports a trade-off between antibiotic resistance and phage sensitivity. This trade-off was maintained over co-evolutionary time scales even under combined phage and antibiotic pressure. Similarly, OMKO1 maintained this trade-off in vivo, again under dual phage/antibiotic pressure. Our findings have implications for the future clinical use of steering in phage therapies. Lay Summary: Given the rise of antibiotic-resistant bacterial infection, new approaches to treatment are urgently needed. Bacteriophages (phages) are bacterial viruses. The use of such viruses to treat infections has been in near-continuous use in several countries since the early 1900s. Recent developments have shown that these viruses are not only effective against routine infections but can also target antibiotic resistant bacteria in a novel, unexpected way. Similar to other lytic phages, these so-called 'steering phages' kill the majority of bacteria directly. However, steering phages also leave behind bacterial variants that resist the phages, but are now sensitive to antibiotics. Treatment combinations of these phages and antibiotics can now be used to greater effect than either one independently. We evaluated the impact of steering using phage OMKO1 and a panel of three antibiotics on Pseudomonas aeruginosa, an important pathogen in hospital settings and in people with cystic fibrosis. Our findings indicate that OMKO1, either alone or in combination with antibiotics, maintains antibiotic sensitivity both in vitro and in vivo, giving hope that phage steering will be an effective treatment option against antibiotic-resistant bacteria.

Bottom-up and top-down control of dispersal across major organismal groups.

Ecology and evolution unfold in spatially structured communities, where dispersal links dynamics across scales. Because dispersal is multicausal, identifying general drivers remains challenging. In a coordinated distributed experiment spanning organisms from protozoa to vertebrates, we tested whether two fundamental determinants of local dynamics, top-down and bottom-up control, generally explain active dispersal. We show that both factors consistently increased emigration rates and use metacommunity modelling to highlight consequences on local and regional dynamics.

Complex life cycle, broad host range and adaptation strategy of the intranuclear Paramecium symbiont Preeria caryophila comb. nov.

Holospora and related bacteria are a group of obligate Paramecium symbionts. Characteristic features are their infectivity, the presence of two distinct morphotypes, and usually a strict specialization for a single Paramecium species as host and for a nuclear compartment (either somatic or generative nucleus) for reproduction. Holospora caryophila steps out of line, naturally occurring in Paramecium biaurelia and Paramecium caudatum. This study addresses the phylogenetic relationship among H. caryophila and other Holospora species based on 16S rRNA gene sequence comparison analyzing the type strain and seven new macronuclear symbionts. Key aspects of Holospora physiology such as infectivity, symbiosis establishment and host range were determined by comprehensive infection assays. Detailed morphological investigations and sequence-based phylogeny confirmed a high similarity between the type strain of H. caryophila and the novel strains. Surprisingly, they are only distantly related to other Holospora species suggesting that they belong to a new genus within the family Holosporaceae, here described as Preeria caryophila comb. nov. Adding to this phylogenetic distance, we also observed a much broader host range, comprising at least eleven Paramecium species. As these potential host species exhibit substantial differences in frequency of sexual processes, P. caryophila demonstrates which adaptations are crucial for macronuclear symbionts facing regular destruction of their habitat.

"French Phage Network"-Second Meeting Report.

The study of bacteriophages (viruses of bacteria) includes a variety of approaches, such as structural biology, genetics, ecology, and evolution, with increasingly important implications for therapeutic and industrial uses. Researchers working with phages in France have recently established a network to facilitate the exchange on complementary approaches, but also to engage new collaborations. Here, we provide a summary of the topics presented during the second meeting of the French Phage Network that took place in Marseille in November 2016.

Evolutionary rescue and local adaptation under different rates of temperature increase: a combined analysis of changes in phenotype expression and genotype frequency in Paramecium microcosms.

Evolutionary rescue (ER) occurs when populations, which have declined due to rapid environmental change, recover through genetic adaptation. The success of this process and the evolutionary trajectory of the population strongly depend on the rate of environmental change. Here we investigated how different rates of temperature increase (from 23 to 32 °C) affect population persistence and evolutionary change in experimental microcosms of the protozoan Paramecium caudatum. Consistent with theory on ER, we found that those populations experiencing the slowest rate of temperature increase were the least likely to become extinct and tended to be the best adapted to the new temperature environment. All high-temperature populations were more tolerant to severe heat stress (35, 37 °C), indicating a common mechanism of heat protection. High-temperature populations also had superior growth rates at optimum temperatures, leading to the absence of a pattern of local adaptation to control (23 °C) and high-temperature (32 °C) environments. However, high-temperature populations had reduced growth at low temperatures (5-9 °C), causing a shift in the temperature niche. In part, the observed evolutionary change can be explained by selection from standing variation. Using mitochondrial markers, we found complete divergence between control and high-temperature populations in the frequencies of six initial founder genotypes. Our results confirm basic predictions of ER and illustrate how adaptation to an extreme local environment can produce positive as well as negative correlated responses to selection over the entire range of the ecological niche.

Antibiotic stress selects against cooperation in the pathogenic bacterium Pseudomonas aeruginosa.

Cheats are a pervasive threat to public goods production in natural and human communities, as they benefit from the commons without contributing to it. Although ecological antagonisms such as predation, parasitism, competition, and abiotic environmental stress play key roles in shaping population biology, it is unknown how such stresses generally affect the ability of cheats to undermine cooperation. We used theory and experiments to address this question in the pathogenic bacterium, Pseudomonas aeruginosa Although public goods producers were selected against in all populations, our competition experiments showed that antibiotics significantly increased the advantage of nonproducers. Moreover, the dominance of nonproducers in mixed cultures was associated with higher resistance to antibiotics than in either monoculture. Mathematical modeling indicates that accentuated costs to producer phenotypes underlie the observed patterns. Mathematical analysis further shows how these patterns should generalize to other taxa with public goods behaviors. Our findings suggest that explaining the maintenance of cooperative public goods behaviors in certain natural systems will be more challenging than previously thought. Our results also have specific implications for the control of pathogenic bacteria using antibiotics and for understanding natural bacterial ecosystems, where subinhibitory concentrations of antimicrobials frequently occur.

Network structure and local adaptation in co-evolving bacteria-phage interactions.

Numerous theoretical and experimental studies have investigated antagonistic co-evolution between parasites and their hosts. Although experimental tests of theory from a range of biological systems are largely concordant regarding the influence of several driving processes, we know little as to how mechanisms acting at the smallest scales (individual molecular and phenotypic changes) may result in the emergence of structures at larger scales, such as co-evolutionary dynamics and local adaptation. We capitalized on methods commonly employed in community ecology to quantify how the structure of community interaction matrices, so-called bipartite networks, reflected observed co-evolutionary dynamics, and how phages from these communities may or may not have adapted locally to their bacterial hosts. We found a consistent nested network structure for two phage types, one previously demonstrated to exhibit arms race co-evolutionary dynamics and the other fluctuating co-evolutionary dynamics. Both phages increased their host ranges through evolutionary time, but we found no evidence for a trade-off with impact on bacteria. Finally, only bacteria from the arms race phage showed local adaptation, and we provide preliminary evidence that these bacteria underwent (sometimes different) molecular changes in the wzy gene associated with the LPS receptor, while bacteria co-evolving with the fluctuating selection phage did not show local adaptation and had partial deletions of the pilF gene associated with type IV pili. We conclude that the structure of phage-bacteria interaction networks is not necessarily specific to co-evolutionary dynamics, and discuss hypotheses for why only one of the two phages was, nevertheless, locally adapted.

Overestimating the Role of Environment in Cancers.

In a recent article, Wu and colleagues (Nature 2016;529:43-47) review previous studies and present new estimates for the contribution of extrinsic factors to cancer development. The new estimates are generally close to 100%, even for bone and brain cancers that have no known associations with lifestyle and are typically not considered to be preventable. We find that the results of Wu and colleagues are incompatible with previous estimates derived from epidemiological and genetic data. We further argue that their methods are fundamentally flawed because they overlook important effects of tissue type on cancer risk. We therefore conclude that their results give a misleading view of cancer etiology and preventability. Cancer Prev Res; 9(10); 773-6. ©2016 AACR.

Dispersal, environmental forcing, and parasites combine to affect metapopulation synehrony and stability.

Dispersal can have positive and negative effects on metapopulation stability and persistence. One prediction is that high levels of dispersal synchronize density fluctuations between subpopulations. However, little is still known about how biotic and abiotic factors combine to modify the effects of dispersal rate on synchrony and metapopulation dynamics. In a fully factorial experimental design, we investigated the combined effects of (1) dispersal, (2) parasite infection, and (3) synchrony in temperature fluctuations on subpopulation synchrony, metapopulation instability, and minimum population size, in laboratory metapopulations of the ciliate Paramecium caudatum. Metapopulations, comprising two subpopulations linked by high or low levels of dispersal, were exposed to daily fluctuations in temperature between permissive (23 degrees C) and restrictive (5 degrees C) conditions. Infected metapopulations started the experiment with one subpopulation uninfected, while the other was infected at a prevalence of 5% with the bacterial parasite Holospora undulata. The temperature synchrony treatment involved subpopulations within a metapopulation following the same (synchronous temperatures) or different (asynchronous temperatures) temporal sequences. Population size was tracked over the 56-day experiment. We found that subpopulation density fluctuations were synchronized by high dispersal in infected metapopulations, and by synchronous temperatures in all metapopulations. Subpopulation synchrony was positively correlated with metapopulation instability and minimum metapopulation size, highlighting the multiple consequences of our treatments for metapopulation dynamics. Our results illustrate how parasites can generate dispersal-driven synchrony in non-cycling, declining populations. This "biotic forcing" via a natural enemy added to the temperature-dependent environmental forcing. We therefore conclude that predictions of metapopulation persistence in natural populations require simultaneous investigation of multiple ecological and epidemiological factors.

Peto's paradox and human cancers.

Peto's paradox is the lack of the expected trend in cancer incidence as a function of body size and lifespan across species. The leading hypothesis to explain this pattern is natural selection for differential cancer prevention in larger, longer lived species. We evaluate whether a similar effect exists within species, specifically humans. We begin by reanalysing a recently published dataset to separate the effects of stem cell number and replication rate, and show that each has an independent effect on cancer risk. When considering the lifetime number of stem cell divisions in an extended dataset, and removing cases associated with other diseases or carcinogens, we find that lifetime cancer risk per tissue saturates at approximately 0.3-1.3% for the types considered. We further demonstrate that grouping by anatomical site explains most of the remaining variation. Our results indicate that cancer risk depends not only on the number of stem cell divisions but varies enormously (approx. 10 000 times) depending on anatomical site. We conclude that variation in risk of human cancer types is analogous to the paradoxical lack of variation in cancer incidence among animal species and may likewise be understood as a result of evolution by natural selection.

Long-term selection experiment produces breakdown of horizontal transmissibility in parasite with mixed transmission mode.

Evolutionary transitions from parasitism toward beneficial or mutualistic associations may encompass a change from horizontal transmission to (strict) vertical transmission. Parasites with both vertical and horizontal transmission are amendable to study factors driving such transitions. In a long-term experiment, microcosm populations of the protozoan Paramecium caudatum and its bacterial parasite Holospora undulata were exposed to three growth treatments, manipulating vertical transmission opportunities over ca. 800 host generations. In inoculation tests, horizontal transmission propagules produced by parasites from a "high-growth" treatment, with elevated host division rates increasing levels of parasite vertical transmission, showed a near-complete loss of infectivity. A similar reduction was observed for parasites from a treatment alternating between high growth and low growth (i.e., low levels of population turn-over). Parasites from a low-growth treatment had the highest infectivity on all host genotypes tested. Our results complement previous findings of reduced investment in horizontal transmission and increased vertical transmissibility of high-growth parasites. We explain the loss of horizontal transmissibility by epidemiological feedbacks and resistance evolution, reducing the frequency of susceptible hosts in the population and thereby decreasing the selective advantage of horizontal transmission. This illustrates how environmental conditions may push parasites with a mixed transmission mode toward becoming vertically transmitted nonvirulent symbionts.