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Engelstaedter, J.

Publications and source records attributed to Engelstaedter, J..

At least 19 recordsLinked to original sources

Metabolic switching promotes microbial coexistence under fluctuating resources

Resource fluctuations can facilitate microbial coexistence when species are sufficiently differentiated in their resource uptake strategies. However, past emphasis on the binary classification of species into equilibrium versus non-equilibrium resource specialists has obscured the potential range of temporal niches available to competitors. Here, we investigate whether microbes that switch between respiratory and fermentative metabolism can coexist with specialist competitors under fluctuations in a single resource. Based on simulations of consumer-resource models, we show that metabolic switching generates distinct growth responses to resource availability, allowing metabolically flexible organisms to exploit temporal variation in ways that differ from specialist strategies. As a result, metabolic switchers can coexist with both respiratory and fermentative specialists under intermediate regimes of resource fluctuation. The competitive ability of metabolic switchers is enhanced when transitions between metabolic states are faster and more responsive to changes in resource availability. Rather than constituting physiological constraints, our results suggest that the metabolic flexibility afforded by overflow metabolism may enable organisms to better exploit fluctuating resources environments.

ecology↗

Shifting resource limitation explains multiphasic patterns of density dependence

Several recent studies have presented sublinear density dependence as a universal phenomenon across species, driven by factors unrelated to resource limitation (e.g. predation or non-resource based inhibition). Through a combination of bacterial growth experiments and mathematical modelling, we instead show that regimes of sublinear density dependence readily emerge under sequential shifts in resource limitation, without the need to invoke other processes. We nevertheless predict that superlinear density dependence, driven by standard resource limitation, will still predominate at both high and low densities.

ecology↗

Strong genotype-by-genotype and genotype-by-environment interactions induced by antibiotic resistance mutations

The often parallel evolution of antibiotic resistance in different species offers a promising basis for predicting evolutionary change. However, the extent to which parallel genetic evolution is reflected at the phenotypic level remains unclear. We investigated how genetic background and temperature influence the fitness effects of homologous rifampicin resistance mutations in absence of antibiotics across two temperatures and three species (Escherichia coli, Acinetobacter baylyi and Lactiplantibacillus plantarum). We measured the effect of resistance mutations on two growth traits (maximum growth rate and maximum optical density) across all conditions and fit linear models to this data using Bayesian inference. Our model fits provide evidence for pervasive genetic interactions in both growth traits, including mutation by species (GxG), mutation by temperature (GxE), and GxGxE interactions. In particular, the effect of resistance mutations was strongly dependent on genomic background, to the extent that mutations often reduced growth in one species but increased it in another (sign epistasis). Similarly, the effect of mutations on growth was strongly influenced by temperature, with some mutations increasing growth at one but decreasing growth at the other temperature. Most notably, three resistance mutations induced strong heat sensitivity in A. baylyi. Our results reinforce previous studies that report strong epistatic and GxE effects of resistance mutations, indicating that in the absence of additional data and more mechanistic models, predicting fitness effects of resistance mutations across species and environments can be very challenging.

evolutionary biology↗

Chimeric Reference Panels for Genomic Imputation

Despite transformative advances in genomic technologies, missing data remains a fundamental constraint that limits the full potential of genomic research across biological systems. Genotype imputation offers a remedy by inferring unobserved genotypes from observed data. However, conventional methods typically rely on external reference panels constructed from complete genome sequences of hundreds of individuals, a costly approach largely inaccessible for non-model organisms. Moreover, these methods generally overlook novel genomic positions not captured in existing panels. To overcome these limitations, we developed Retriever, a framework that bypasses the need for external reference panels. Retriever constructs a chimeric reference panel directly from the target samples using a sliding-window approach to identify and retrieve genomic partitions with complete data. By exploiting the complementary distribution of missing data across samples, Retriever assembles a panel that preserves local patterns of linkage disequilibrium and captures novel variants. Integrated with Beagle, Retriever achieves genotype imputation with accuracy consistently exceeding 95% across diverse datasets, including plants, animals, and fungi. By eliminating the need for costly external panels, Retriever offers an accessible, cost-effective solution that broadens the application of sophisticated genomic analyses across species.

bioinformatics↗

The genetic architecture of polygenic adaptation under a network-derived trait

The genetic architecture of adaptation varies across species, populations, and traits. While existing models capture aspects like the number of loci, effect sizes, and allele frequencies, they often overlook the molecular processes underlying trait expression. We investigated how gene regulatory networks influence quantitative variation during adaptation by examining the negative autoregulation (NAR) motif in two configurations: K+, with four evolving network components, and K-, with two components. Using forward-time simulations, we tracked populations adapting to a shifted phenotypic optimum under varying genetic architectures. We found that K+ populations maintained rapid adaptation despite low recombination, preserving high genetic variance through positive epistasis and stronger linkage disequilibrium. Under low recombination, K+ populations reached the optimum through diverse molecular configurations, while responses were more uniform under high recombination. In contrast, K- and additive models showed impaired adaptation under low recombination. Our findings demonstrate that network structure fundamentally influences the distribution of variation within the molecular architecture of traits, with certain networks providing unexpected robustness against low recombination rates. This suggests that molecular complexity may confer evolutionary advantages in natural populations.

evolutionary biology↗

Evolution and evolvability of rifampicin resistance across the bacterial tree of life

Predicting the ability of bacteria to develop antibiotic resistance is challenging, especially for the vast majority of species for which no experimental data are available. Here, we investi-gated the evolvability and intrinsic presence of rifampicin resistance across the bacterial tree of life. We compiled a panel of known rifampicin resistance mutations, comprising 60 amino acid substitutions within the gene rpoB. We then screened > 18 000 genomes from all major bac-terial groups for the presence of those mutations and determined which mutations can evolve through point mutations. Our results demonstrate that although the evolvability of individual mutations varies considerably across species, overall predicted evolvability is high and relatively homogeneous across bacterial taxa. Rifampicin resistance mutations are present intrinsically in 8% of species. Our analysis provides a global picture of the mutational landscape of rifampicin resistance, including both insight into existing observations as well as predictions informing future work.

evolutionary biology↗

A unifying principle for multispecies coexistence under resource fluctuations

Resource fluctuations are ubiquitous in nature and yet are generally assumed to play a limited role in the maintenance of biodiversity. We challenge this assumption by analyzing resource competition dynamics under conditions where traditional theory fails. We show that multi-species coexistence can be sustained when species are able to specialise on different temporal patterns of resource variability, including the asymmetries and periodic extremes commonly observed in natural systems. We further show how this partitioning of the statistical moments of the resource distribution provides a unified framework for explaining coexistence in variable resource environments. A theory of diversity maintenance based on moment partitioning highlights the potential for anthropogenic changes in resource regimes to drive cascading biodiversity losses.

ecology↗

Optimal antimicrobial dosing combinations when drug-resistance mutation rates differ

Given the ongoing antimicrobial resistance crisis, it is imperative to develop dosing regimens optimised to avoid the evolution of resistance. The rate at which bacteria acquire resistance-conferring mutations to different antimicrobial drugs spans multiple orders of magnitude. By using a mathematical model and computer simulations, we show that knowledge of relative mutation rates can meaningfully inform the optimal combination of two drugs in a treatment regimen. We demonstrate that under plausible assumptions there is a linear relationship in log-log space between the drug A:drug B dose ratio that maximises the chance of treatment success and the ratio of their mutation rates. This power law relationship holds for bacteriostatic and bactericidal drugs. If borne out empirically, these findings suggest there might be significant room to further optimise antimicrobial dosing strategies.

evolutionary biology↗

The distribution of fitness effects during adaptive walks using a simple genetic network

The tempo and mode of adaptation depends on the availability of beneficial alleles. Genetic interactions arising from gene networks can restrict this availability. However, the extent to which networks affect adaptation remains largely unknown. Current models of evolution consider additive genotype-phenotype relationships while often ignoring the contribution of gene interactions to phenotypic variance. In this study, we model a quantitative trait as the product of a simple gene regulatory network, the negative autoregulation motif. Using forward-time genetic simulations, we measure adaptive walks towards a phenotypic optimum in both additive and network models. A key expectation from adaptive walk theory is that the distribution of fitness effects of new beneficial mutations is exponential. We found that both models instead harbored distributions with fewer large-effect beneficial alleles than expected. The network model also had a complex and bimodal distribution of fitness effects among all mutations, with a considerable density at deleterious selection coefficients. This behavior is reminiscent of the cost of complexity, where correlations among traits constrain adaptation. Our results suggest that the interactions emerging from genetic networks can generate complex and multimodal distributions of fitness effects.

evolutionary biology↗

Belt and braces: two escape ways to maintain the cassette reservoir of large chromosomal integrons

Integrons are adaptive devices that capture, stockpile, shuffle and express gene cassettes thereby sampling combinatorial phenotypic diversity. Some integrons called sedentary chromosomal integrons (SCIs) can be massive structures containing hundreds of cassettes. Since most of these cassettes are non-expressed, it is not clear how they remain stable over long evolutionary timescales. Recently, it was found that the experimental inversion of the SCI of Vibrio cholerae led to a dramatic increase of the cassette excision rate associated to a fitness defect. Here, we question the evolutionary sustainability of this apparently counter selected genetic context through experimental evolution. We find that the integrase is rapidly inactivated and that the inverted SCI can recover its original orientation by homologous recombination between two insertion sequences (ISs) present in the array. These two outcomes of SCI inversion restore the normal growth and prevent the loss of cassettes, enabling SCIs to retain their roles as reservoirs of functions. These results illustrate an interesting interplay between gene orientation, genome rearrangement, bacterial fitness and demonstrate how integrons can benefit from their embedded ISs.

genetics↗

Frequent, infinitesimal bottlenecks maximize the rate of microbial adaptation

Serial passaging is a fundamental technique in experimental evolution. The choice of bottleneck severity and frequency poses a dilemma: longer growth periods allow beneficial mutants to arise and grow over more generations, but simultaneously necessitate more severe bottlenecks with a higher risk of those same mutations being lost. Short growth periods require less severe bottlenecks, but come at the cost of less time between transfers for beneficial mutations to establish. The standard laboratory protocol of 24-hour growth cycles with severe bottlenecking has logistical advantages for the experimenter but limited theoretical justification. Here we demonstrate that contrary to standard practice, the rate of adaptive evolution is maximized when bottlenecks are frequent and small, indeed infinitesimally so in the limit of continuous culture. This result derives from revising key assumptions underpinning previous theoretical work, including changing the metric of optimization to incorporate experiment runtime, and using a full binomial distribution for bottlenecking, rather than a Poisson approximation. We also show that adding resource constraints and clonal interference to the model leaves the qualitative results unchanged. Implementing these findings will require liquid-handling robots to perform frequent bottlenecks, or chemostats for continuous culture. Further innovation in and adoption of these technologies has the potential to accelerate the rate of discovery in experimental evolution.

genetics↗

Host phylogeny and ecological associations best explain Wolbachia host shifts in scale insects

Wolbachia are among the most prevalent and widespread endosymbiotic bacteria on earth. Wolbachia s success in infecting an enormous number of arthropod species is attributed to two features: the range of phenotypes they induce in their hosts, and their ability to switch to new host species. Whilst much progress has been made in elucidating the phenotypes induced by Wolbachia, our understanding of Wolbachia host shifting is still very limited: we lack answers to even fundamental questions concerning Wolbachias routes of transfer and the importance of factors influencing host shifts. Here, we investigate the diversity and host-shift patterns of Wolbachia in scale insects, a group of arthropods with intimate associations with other insects that make them well-suited to studying host shifts. Using Illumina pooled amplicon sequencing of Wolbachia-infected scale insects and their direct associates we determined the identity of all Wolbachia strains, revealing that 32% of samples were multiply infected (with up to five distinct strains per species). We then fitted a Generalised Additive Mixed Model (GAMM) to our data to estimate the influence of factors such as the host phylogeny and the geographic distribution of each species on Wolbachia strain sharing among scale insect species. The model predicts no significant contribution of host geography but strong effects of host phylogeny, with high rates of Wolbachia sharing among closely related species and a sudden drop-off in sharing with increasing phylogenetic distance. We also detected the same Wolbachia strain in scale insects and several intimately associated species (ants, wasps, beetles, and flies). This indicates putative host shifts and potential routes of transfers via these associates and highlights the importance of ecological connectivity in Wolbachia host-shifting.

evolutionary biology↗

Wolbachia in scale insects: a distinct pattern of infection frequencies and potential transfer routes via ant associates

Wolbachia is one of the most successful endosymbiotic bacteria of arthropods. Known as the "master of manipulation", Wolbachia can induce a wide range of phenotypes in its host that can have far-reaching ecological and evolutionary consequences and may be exploited for disease and pest control. However, our knowledge of Wolbachias distribution and infection rate is unevenly distributed across arthropod groups such as scale insects. We fitted a distribution of within-species prevalence of Wolbachia to our data and compared it to distributions fitted to an up-to-date dataset compiled from surveys across all arthropods. The estimated distribution parameters indicate a Wolbachia infection frequency of 43.6% (at a 10% prevalence threshold) in scale insects. Prevalence of Wolbachia in scale insects follows a distribution similar to exponential decline (most species are predicted to have low prevalence infections), in contrast to the U-shaped distribution estimated for other taxa (most species have a very low or very high prevalence). We observed no significant associations between Wolbachia infection and scale insect traits. Finally, we screened for Wolbachia in scale insects ecological associates. We found a positive correlation between Wolbachia infection in scale insects and their ant associates, pointing to a possible route of horizontal transfer of Wolbachia. Originality-Significance StatementBy creating metadata of Wolbachia infection in arthropods and applying a fitting an advanced mathematical model on the estimated infection frequency in scale insects, a unique pattern of infection prevalence was detected. In addition, ant-scale insect trophallaxis interaction was suggested as a plausible route of Wolbachia transfer

microbiology↗

Genetic slippage after sex maintains diversity for parasite resistance in a natural host population

Although parasite-mediated selection is thought to be a major driver of host evolution, its influence on genetic variation for parasite resistance is not yet well understood. We monitored a large population of the planktonic crustacean Daphnia magna over eight years, as it underwent yearly epidemics of the bacterial pathogen Pasteuria ramosa. We observed a cyclical pattern of resistance evolution: resistant phenotypes increased in frequency throughout the epidemics, but susceptibility was restored each spring when hosts hatched from sexual resting stages, a phenomenon described as genetic slippage in response to sex. Collecting and hatching D. magna resting stages across multiple seasons showed that largely resistant host populations can produce susceptible offspring through recombination. Resting stages produced throughout the planktonic season accurately represent the hatching population cohort of the following spring. A genetic model of resistance developed for this host-parasite system, based on multiple loci and strong epistasis, is in partial agreement with these findings. Our results reveal that, despite strong selection for resistance in a natural host population, genetic slippage after sexual reproduction has the potential to maintain genetic diversity of host resistance.

evolutionary biology↗

A two-locus system with strong epistasis underlies rapid parasite-mediated evolution of host resistance

Parasites are a major evolutionary force, driving adaptive responses in host populations. Although the link between phenotypic response to parasite-mediated natural selection and the underlying genetic architecture often remains obscure, this link is crucial for understanding the evolution of resistance and predicting associated allele frequency changes in the population. To close this gap, we monitored the response to selection during epidemics of a virulent bacterial pathogen, Pasteuria ramosa, in a natural host population of Daphnia magna. Across two epidemics, we observed a strong increase in the proportion of resistant phenotypes as the epidemics progressed. Field and laboratory experiments confirmed that this increase in resistance was caused by selection from the local parasite. Using a genome wide association study (GWAS), we obtained a genetic model in which two genomic regions with dominance and epistasis control resistance polymorphism in the host. We verified this model by selfing host genotypes with different resistance phenotypes and scoring their F1 for segregation of resistance and associated genetic markers. Applying the model to the dynamics of the field population revealed moderate changes in allele frequencies at the two resistance loci relative to the profound changes observed at the phenotypic level. This apparent discrepancy is explained by strong epistasis and dominance at the two resistance loci, which reduces the effect of selection on alleles at both loci. Such epistatic effects with strong fitness consequences in host-parasite coevolution are believed to be crucial in the Red Queen model for the evolution of genetic recombination.

evolutionary biology↗

Highly replicated evolution of parapatric ecotypes

Parallel evolution of ecotypes occurs when selection independently drives the evolution of similar traits across similar environments. The multiple origin of ecotypes is often inferred on the basis of a phylogeny which clusters populations according to geographic location and not by the environment they occupy. However, the use of phylogenies to infer parallel evolution in closely related populations is problematic because gene flow and incomplete lineage sorting can uncouple the genetic structure at neutral markers from the colonization history of populations. Here, we demonstrate multiple origins within ecotypes of an Australian wildflower, Senecio lautus. We observed strong genetic structure as well as phylogenetic clustering by geography and show that this is unlikely due to gene flow between parapatric ecotypes, which is surprisingly low. We further confirm this analytically by demonstrating that phylogenetic distortion due to gene flow often requires higher levels of migration than those observed in S. lautus. Our results imply that selection can repeatedly create similar phenotypes despite the perceived homogenizing effects of gene flow.

evolutionary biology↗

A framework to quantify phenotypic and genotypic parallel evolution

The independent and repeated adaptation of populations to similar environments often results in the evolution of similar forms. This phenomenon creates a strong correlation between phenotype and environment and is referred to as parallel evolution. However, we are still largely unaware of the dynamics of parallel evolution, as well as the interplay between phenotype and genotype within natural systems. Here, we examined phenotypic and genotypic parallel evolution in multiple parapatric Dune-Headland coastal ecotypes of an Australian wildflower, Senecio lautus. We observed a clear trait-environment association within the system, with all replicate populations having evolved along the same phenotypic evolutionary trajectory. Similar phenotypes have arisen via mutational changes occurring in different genes, although many share the same biological functions. Our results shed light on how replicated adaptation manifests at the phenotypic and genotypic levels within populations, and highlights S. lautus as one of the most striking cases of phenotypic parallel evolution in nature.

evolutionary biology↗

Mutators as drivers of adaptation in pathogenic bacteria and a risk factor for host jumps and vaccine escape: insights into evolutionary epidemiology of the global aquatic pathogen Streptococcus iniae

Pathogens continuously adapt to changing host environments where variation in their virulence and antigenicity is critical to their long-term evolutionary success. The emergence of novel variants is accelerated in microbial mutator strains (mutators) deficient in DNA repair genes, most often from mismatch repair and oxidised-guanine repair systems (MMR and OG respectively). Bacterial MMR/OG mutants are abundant in clinical samples and show increased adaptive potential in experimental infection models, yet the role of mutators in the epidemiology and evolution of infectious disease is not well understood. Here we investigated the role of mutation rate dynamics in the evolution of a broad host range pathogen, Streptococcus iniae, using a set of 80 strains isolated globally over 40 years. We have resolved phylogenetic relationships using non-recombinant core genome variants, measured in vivo mutation rates by fluctuation analysis, identified variation in major MMR/OG genes and their regulatory regions, and phenotyped the major traits determining virulence in streptococci. We found that both mutation rate and MMR/OG genotype are remarkably conserved within phylogenetic clades but significantly differ between major phylogenetic lineages. Further, variation in MMR/OG loci correlates with occurrence of atypical virulence-associated phenotypes, infection in atypical hosts (mammals), and atypical tissue of a vaccinated primary hosts (barramundi bone). These findings suggest that mutators are likely to facilitate adaptations preceding major diversification events, and may promote emergence of variation permitting colonisation of a novel host tissue, novel host taxa (host jumps), and immune-escape in the vaccinated host.

microbiology↗