Michael Manhart


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Manhart

First Name

Michael

ORCID

0000-0003-3791-9056

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Publications1 - 8 of 8
  • Microbial population dynamics decouple growth response from environmental nutrient concentration
    Item type: Journal Article
    Fink, Justus; Held, Noelle A.; Manhart, Michael (2023)
    Proceedings of the National Academy of Sciences of the United States of America
    How the growth rate of a microbial population responds to the environmental availability of chemical nutrients and other resources is a fundamental question in microbiology. Models of this response, such as the widely used Monod model, are generally characterized by a maximum growth rate and a half-saturation concentration of the resource. What values should we expect for these half-saturation concentrations, and how should they depend on the environmental concentration of the resource? We survey growth response data across a wide range of organisms and resources. We find that the half-saturation concentrations vary across orders of magnitude, even for the same organism and resource. To explain this variation, we develop an evolutionary model to show that demographic fluctuations (genetic drift) can constrain the adaptation of half-saturation concentrations. We find that this effect fundamentally differs depending on the type of population dynamics: Populations undergoing periodic bottlenecks of fixed size will adapt their half-saturation concentrations in proportion to the environmental resource concentrations, but populations undergoing periodic dilutions of fixed size will evolve half-saturation concentrations that are largely decoupled from the environmental concentrations. Our model not only provides testable predictions for laboratory evolution experiments, but it also reveals how an evolved half-saturation concentration may not reflect the organism's environment. In particular, this explains how organisms in resource-rich environments can still evolve fast growth at low resource concentrations. Altogether, our results demonstrate the critical role of population dynamics in shaping fundamental ecological traits.
  • Understanding the evolution of interspecies interactions in microbial communities
    Item type: Journal Article
    Gorter, Florien A.; Manhart, Michael; Ackermann, Martin (2020)
    Philosophical Transactions of the Royal Society B: Biological Sciences
    Microbial communities are complex multi-species assemblages that are characterized by a multitude of interspecies interactions, which can range from mutualism to competition. The overall sign and strength of interspecies interactions have important consequences for emergent community-level properties such as productivity and stability. It is not well understood how interspecies interactions change over evolutionary timescales. Here, we review the empirical evidence that evolution is an important driver of microbial community properties and dynamics on timescales that have traditionally been regarded as purely ecological. Next, we briefly discuss different modelling approaches to study evolution of communities, emphasizing the similarities and differences between evolutionary and ecological perspectives. We then propose a simple conceptual model for the evolution of interspecies interactions in communities. Specifically, we propose that to understand the evolution of interspecies interactions, it is important to distinguish between direct and indirect fitness effects of a mutation. We predict that in well-mixed environments, traits will be selected exclusively for their direct fitness effects, while in spatially structured environments, traits may also be selected for their indirect fitness effects. Selection of indirectly beneficial traits should result in an increase in interaction strength over time, while selection of directly beneficial traits should not have such a systematic effect. We tested our intuitions using a simple quantitative model and found support for our hypotheses. The next step will be to test these hypotheses experimentally and provide input for a more refined version of the model in turn, thus closing the scientific cycle of models and experiments. This article is part of the theme issue ‘Conceptual challenges in microbial community ecology’.
  • Chromosomal barcoding of E. coli populations reveals lineage diversity dynamics at high resolution
    Item type: Journal Article
    Jasinska, Weronika; Manhart, Michael; Lerner, Jesse; et al. (2020)
    Nature Ecology & Evolution
  • Evolution of Microbial Growth Traits Under Serial Dilution
    Item type: Journal Article
    Lin, Jie; Manhart, Michael; Amir, Ariel (2020)
    Genetics
    Selection of mutants in a microbial population depends on multiple cellular traits. In serial-dilution evolution experiments, three key traits are the lag time when transitioning from starvation to growth, the exponential growth rate, and the yield (number of cells per unit resource). Here, we investigate how these traits evolve in laboratory evolution experiments using a minimal model of population dynamics, where the only interaction between cells is competition for a single limiting resource. We find that the fixation probability of a beneficial mutation depends on a linear combination of its growth rate and lag time relative to its immediate ancestor, even under clonal interference. The relative selective pressure on growth rate and lag time is set by the dilution factor; a larger dilution factor favors the adaptation of growth rate over the adaptation of lag time. The model shows that yield, however, is under no direct selection. We also show how the adaptation speeds of growth and lag depend on experimental parameters and the underlying supply of mutations. Finally, we investigate the evolution of covariation between these traits across populations, which reveals that the population growth rate and lag time can evolve a nonzero correlation even if mutations have uncorrelated effects on the two traits. Altogether these results provide useful guidance to future experiments on microbial evolution. © 2020 by the Genetics Society of America.
  • Nutrient colimitation is a quantitative, dynamic property of microbial populations
    Item type: Journal Article
    Held, Noelle A.; Krishna, Aswin; Crippa, Donat; et al. (2024)
    Proceedings of the National Academy of Sciences of the United States of America
    Resource availability dictates how fast and how much microbial populations grow. Quantifying the relationship between microbial growth and resource concentrations makes it possible to promote, inhibit, and predict microbial activity. Microbes require many resources, including macronutrients (e.g., carbon and nitrogen), micronutrients (e.g., metals), and complex nutrients like vitamins and amino acids. When multiple resources are scarce, as frequently occurs in nature, microbes may experience resource colimitation in which more than one resource simultaneously limits growth. Despite growing evidence for colimitation, the data are difficult to interpret and compare due to a lack of quantitative measures of colimitation and systematic tests of resource conditions. We hypothesize that microbes experience a continuum of nutrient limitation states and that nutrient colimitation is common in the laboratory and in nature. To address this, we develop a quantitative theory of resource colimitation that captures the range of possible limitation states and describes how they can change dynamically with resource conditions. We apply this approach to clonal populations of Escherichia coli to show that colimitation occurs in common laboratory conditions. We also show that growth rate and growth yield are colimited differently, reflecting the different underlying biology of these traits. Finally, we analyze environmental data to provide intuition for the continuum of limitation and colimitation conditions in nature. Altogether our results provide a quantitative framework for understanding and quantifying colimitation of microbes in biogeochemical, biotechnology, and human health contexts.
  • How do microbes grow in nature? The role of population dynamics in microbial ecology and evolution
    Item type: Review Article
    Fink, Justus Wilhelm; Manhart, Michael (2023)
    Current Opinion in Systems Biology
    The growth of microbial populations in nature is dynamic, as the cellular physiology and environment of these populations change. Population dynamics have wide-ranging consequences for ecology and evolution, determining how species interact and which mutations fix. Understanding these dynamics is also critical for clinical and environmental applications in which we need to promote or inhibit microbial growth. We first address the latest efforts and outstanding challenges in measuring microbial population dynamics in natural environments. We next summarize fundamental concepts and empirical data on how population dynamics both shape and are shaped by evolutionary processes. Finally, we discuss the role of tradeoffs in microbial population dynamics, which may reveal physiological constraints and help to maintain ecological diversity. We find that current evidence for tradeoffs in population dynamics is limited, but that consideration of the evolutionary context of these tradeoffs is necessary for designing future experiments that can better address this problem.
  • Evolutionary regain of lost gene circuit function
    Item type: Journal Article
    Gouda, Mirna K.; Manhart, Michael; Balázsi, Gábor (2019)
    Proceedings of the National Academy of Sciences of the United States of America
    Evolutionary reversibility—the ability to regain a lost function—is an important problem both in evolutionary and synthetic biology, where repairing natural or synthetic systems broken by evolutionary processes may be valuable. Here, we use a synthetic positive-feedback (PF) gene circuit integrated into haploid Saccharomyces cerevisiae cells to test if the population can restore lost PF function. In previous evolution experiments, mutations in a gene eliminated the fitness costs of PF activation. Since PF activation also provides drug resistance, exposing such compromised or broken mutants to both drug and inducer should create selection pressure to regain drug resistance and possibly PF function. Indeed, evolving 7 PF mutant strains in the presence of drug revealed 3 adaptation scenarios through genomic, PF-external mutations that elevate PF basal expression, possibly by affecting transcription, translation, degradation, and other fundamental cellular processes. Nonfunctional mutants gained drug resistance without ever developing high expression, while quasifunctional and dysfunctional PF mutants developed high expression nongenetically, which then diminished, although more slowly for dysfunctional mutants where revertant clones arose. These results highlight how intracellular context, such as the growth rate, can affect regulatory network dynamics and evolutionary dynamics, which has important consequences for understanding the evolution of drug resistance and developing future synthetic biology applications.
Publications1 - 8 of 8