Biology subjects

Metcalf, C. J. E.

Publications and source records attributed to Metcalf, C. J. E..

11 recordsLinked to original sources

bioRxiv2025

The future burden of congenital Toxoplasmosis in Africa under demographic and climate change

The impact of climate change on environmental pathogens is a question whose importance will amplify in coming years. The protozoan parasite and global zoonosis Toxoplasma gondii is one such: empirical evidence indicates that oocyst survival is reduced at high temperatures. Paradoxically, a decline in incidence of T. gondii infections could amplify the burden of this disease, as the most damaging outcome occurs subsequent to first infection during pregnancy, and reductions in the incidence of the infection will increase the average age of first infection. We blend models of infection dynamics rooted in occurrence across the African continent with models of human demography to bound expectations for the future burden of this pathogen, accounting for the effects of changing temperatures. We discuss targeting efforts and approaches for mitigation.

ecology↗

bioRxiv2024

Eco-evolutionary dynamics of pathogen immune-escape: deriving a population-level phylodynamic curve

The phylodynamic curve [1] conceptualizes how immunity shapes the rate of viral adaptation in a non-monotonic fashion, through its opposing effects on viral abundance and the strength of selection. However, concrete and quantitative model realizations of this influential concept are rare. Here, we present an analytic, stochastic framework in which a population-scale phylodynamic curve emerges dynamically, allowing us to address questions regarding the risk and timing of emergence of viral immune escape variants. We explore how pathogen- and population-specific parameters such as strength of immunity, transmissibility and antigenic constraints affect the phylodynamic curve, leading to distinct phylodynamic curves for different pathogens. Motivated by the COVID-19 pandemic, we probe the likely effects of non-pharmaceutical interventions (NPIs), and the lifting thereof, on the risk of viral escape variant emergence. Looking ahead, the framework has the potential to become a useful tool for probing how natural immunity, as well as choices in vaccine design and distribution and the implementation of NPIs affect the evolution of common viral pathogens.

ecology↗

bioRxiv2024

The ontogeny of immune tolerance: a model of the early-life gut microbiome and adaptive immunity

To achieve immune and microbial homeostasis during adulthood, the developing immune system must learn to identify which microbes to tolerate and which to defend against. How such immune education unfolds remains a major knowledge gap. We address this gap by synthesizing existing literature to develop a mechanistic mathematical model representing the interplay between gut ecology and adaptive immunity in early life. Our results indicate that the inflammatory tone of the microenvironment is the mediator of information flow from pre- to post-weaning periods. We evaluate the power of postnatal fecal samples for predicting immunological trajectories and explore breastfeeding scenarios when maternal immunological conditions affect breastmilk composition. Our work establishes a quantitative basis for immune education, yielding insights into questions of applied relevance.

immunology↗

bioRxiv2023

Transmission mode shapes host specialization of the phyllosphere microbiome

The collection of microorganisms inhabiting aboveground plant tissue, termed the phyllosphere microbiome, is shaped by both microbial dispersal and host filtering effects. Because plants often occur in multispecies assemblages, microbiome diversity is likely shaped by plant community composition through microbial transmission between conspecific (same species) and heterospecific (different species) host plants. Although rarely examined, the relative incidence of con-versus heterospecific transmission should impact microbiome-level specialization. Using four species of plants we experimentally tested this idea by passaging an initially diverse microbial community either between conspecific or heterospecific plants in the greenhouse. While conspecific transmission lines exhibited persistent host effects, these effects decreased in the heterospecific transmission lines, suggesting a shift towards more generalist microbiomes. Similarly, when microbiomes were transplanted onto a set of novel host plant species, host effects were weaker for these heterospecific lines than the conspecific lines. Finally, microbiomes conspecifically passaged on tomato plants were found to outcompete those passaged on either bean or pepper when co-inoculated onto tomato hosts, suggesting microbiome-level host specialization under conspecific transmission. Overall, we find that both transmission mode and host association history shape microbiome diversity, that repeated conspecific transmission results in microbiome specialization, and that repeated heterospecific transmission can drive microbiomes to develop generalist characteristics.

ecology↗

bioRxiv2022

Relative abundance data can misrepresent heritability of the microbiome

Host genetics can shape microbiome composition, but to what extent it does, remains unclear. Like any other complex trait, this question can be addressed by estimating the heritability (h2) of the microbiome - the proportion of variance in the abundance of each taxon that is attributable to host genetic variation. However, unlike most complex traits, microbiome heritability is typically based on relative abundance data, where taxon-specific abundances are expressed as the proportion of the total microbial abundance in a sample. We derived an analytical approximation for the heritability that one obtains when using such relative abundances and we uncovered three problems: 1) The interdependency between taxa leads to imprecise heritability estimates. 2) Large sample size leads to high false discovery rates, overestimating the number of heritable taxa. 3) Microbial co-abundances lead to biased heritability estimates. We conclude that caution must be taken when interpreting heritability estimates and comparing values across studies.

evolutionary biology↗

bioRxiv2021

Plant neighborhood shapes diversity and reduces interspecific variation of the phyllosphere microbiome

Microbial communities associated with plant leaf surfaces (i.e. the phyllosphere) are increasingly recognized for their role in plant health. While accumulating evidence suggests a role for host filtering of its microbiota, far less is known about how community composition is shaped by dispersal, including from neighboring plants. We experimentally manipulated the local plant neighborhood within which tomato, pepper, or bean plants were grown in a three-month field trial. Focal plants were grown in the presence of con- or hetero-specific neighbors (or no neighbors) in a fully factorial combination. At 30-day intervals, focal plants were harvested and replaced with a new age- and species-matched cohort while allowing neighborhood plants to continue growing. 16S community profiling revealed that the strength of host filtering effects (i.e. interspecific differences in composition) decreased over time. In contrast, the strength of neighborhood effects increased over time, suggesting dispersal from neighboring plants becomes more important as neighboring plant biomass increases. We next implemented a cross-inoculation study in the greenhouse using inoculum generated from the field plants to directly test host filtering of microbiomes while controlling for directionality and source of dispersal. This experiment further demonstrated that focal host species, the host from which the microbiome came, and in one case the donor hosts neighbors, contribute to variation in phyllosphere bacterial composition. Overall, our results suggest that local dispersal is a key factor in phyllosphere assembly, and that demographic factors such as nearby neighbor identity and biomass or age are important determinants of phyllosphere microbiome diversity.

ecology↗

bioRxiv2021

Optimal immune specificity at the intersection of host life history and parasite epidemiology

Epidemiology and life history are commonly hypothesized to influence host immune strategy, and the pairwise relationships between immune strategy and each factor have been extensively investigated. But the interaction of these two is rarely considered, despite evidence that this interaction might produce emergent effects on optimal immune strategy. Here we investigate the confluence of epidemiology and life history as it affects immune strategy through a demographically-framed model of sensitivity and specificity in parasite recognition and response. We find that variation in several different life history traits associated with both reproduction and longevity alters optimal immune strategies - but the direction and magnitude of these effects depends on how epidemiological risks vary across life. Drawing on published life history data, we also find that our predictions apply across chordate taxa. Our results shed light on the complex interactions shaping immune strategy and may prove valuable in interpreting empirical results in ecoimmunology.

ecology↗

bioRxiv2020

When the microbiome defines the host phenotype: selection on vertical transmission in varying environments

The microbiome can contribute to variation in fitness-related traits of their hosts, and thus to host evolution. Hosts are therefore expected to be under selection to control their microbiome, for instance through controlling microbe transmission from parents to offspring. Current models have mostly focused on microbes that either increase or decrease fitness. In that case, host-level selection is relatively straightforward, favouring either complete or no inheritance. In natural systems, however, vertical transmission fidelity varies widely, and microbiome composition is often shaped by a combination of vertical and horizontal transmission modes. We propose that such mixed transmission could optimize host fitness under fluctuating environments. Using a general model, we illustrate that decreasing vertical transmission fidelity increases the amount of microbiome variation, and thus potentially phenotypic variation, across hosts. Whether or not this is advantageous depends on environmental conditions, how much the microbiome changes during host development, and the contribution of other factors to trait variation. We discuss how environmentally-dependent microbial effects can favor intermediate transmission, review examples from natural systems, and suggest research avenues to empirically test our predictions. Overall, we show that imperfect transmission may be adaptive by allowing individuals to ensure phenotypic variability in their offspring in contexts where varying environments mean that this strategy increases long-term fitness.

evolutionary biology↗

bioRxiv2019

Why evolve reliance on the microbiome for timing of ontogeny?

The timing of life history events has important fitness consequences. Since the 1950s, researchers have combined first principles and data to predict the optimal timing of life history transitions. Recently, a striking mystery has emerged. Such transitions can be shaped by a completely different branch of the tree of life: bacterial species in the microbiome. Probing these interactions using testable predictions from evolutionary theory could illuminate whether and how host-microbiome integrated life histories can evolve and be maintained. Beyond advancing fundamental science, this research program could yield important applications. In an age of microbiome engineering, understanding the contexts that lead to microbiota signaling shaping ontogeny could offer novel mechanisms for manipulations to increase yield in agriculture, or reduce pathogen transmission by affecting vector efficiency. We combine theory and evidence to illuminate the essential questions underlying the existence of Microbiome Dependent Ontogenetic Timing (MiDOT) to fuel research on this emerging topic.

evolutionary biology↗

bioRxiv2019

Successive passaging of a plant-associated microbiome reveals robust habitat and host genotype-dependent selection

There is increasing interest in the plant microbiome as it relates to both plant health and agricultural sustainability. One key unanswered question is whether we can select for a plant microbiome that is robust after colonization of target hosts. We used a successive passaging experiment to address this question by selecting upon the tomato phyllosphere microbiome. Beginning with a diverse microbial community generated from field-grown tomato plants, we inoculated replicate plants across five plant genotypes for four eight-week long passages, sequencing the microbial community at each passage. We observed consistent shifts in both the bacterial (16S amplicon sequencing) and fungal (ITS amplicon sequencing) communities across replicate lines over time, as well as a general loss of diversity over the course of the experiment suggesting that much of the naturally observed microbial community in the phyllosphere is likely transient or poorly adapted. We found that both host genotype and environment shape microbial composition, but the relative importance of genotype declines through time. Furthermore, using a community coalescence experiment, we found that the bacterial community from the end of the experiment was robust to invasion by the starting bacterial community. These results highlight that selecting for a stable microbiome that is well adapted to a particular host environment is indeed possible, emphasizing the great potential of this approach in agriculture and beyond.\n\nSignificance StatementThere is great interest in selecting for host-associated microbiomes that confer particular functions to their host, and yet it remains unknown whether selection for a robust and stable microbiome is possible. Here, we use a microbiome passaging approach to measure the impact of host-mediated selection on the tomato phyllosphere (above ground) microbiome. We find robust community selection across replicate lines that is shaped by plant host genotype in early passages, but changes in a genotype-independent manner in later passages. Work such as ours is crucial to understanding the general principles governing microbiome assembly and adaptation, and is widely applicable to both sustainable agriculture and microbiome-related medicine.

microbiology↗

bioRxiv2018

Perfect Counterfactuals for Epidemic Simulations

Simulation studies are often used to predict the expected impact of control measures in infectious disease outbreaks. Typically, two independent sets of simulations are conducted, one with the intervetnion, and one without, and epidemic sizes (or some related metric) are compared to estimate the effect of the intervention. Since it is possible that controlled epidemics are larger than uncontrolled ones if there is substantial stochastic variation between epidemics, uncertainty intervals from this approach can include a negative effect even for an effective intervention. To more precisely estimate the number of cases an intervention will prevent within a single epidemic, here we develop a single world approach to matching simulations of controlled epidemics to their exact uncontrolled counterfac-tual. Our method borrows concepts from percolation approaches prune out possible epidemic histories and create potential epidemic graph that can be realized to create perfectly matched controlled and uncontrolled epidemics. We present an implementation of this method for a common class of compartmental models, and its application in a simple SIR model. Results illustrate how, at the cost of some computation time, this method substantially narrows confidence intervals and avoids non-sensical inferences.

epidemiology↗