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Seppe Kuehn

Publications and source records attributed to Seppe Kuehn.

6 recordsLinked to original sources

Natural Selection in the Wake of Catastrophe

Living organisms, from bacteria to humans, are more likely to survive if their traits enhance fitness. In populations well adapted to their environmental niches, natural selection proceeds via rarely beneficial mutations. But when a catastrophe wipes out niche diversity, sudden adaptation often follows. Here, we present a data-validated theory of natural selection in the wake of catastrophe and unveil a simple law that emerges during recovery: the mean fitness relaxes inversely with time, with a prefactor proportional to the number of traits coupled to the post-catastrophe environment. We put our approach to test using experimental fitness landscapes measured following antibiotic administration to E. coli. The resulting mean trait adaptation is not described by gradient ascent on a fitness landscape, instead it follows an algorithm known as Levenberg-Marquardt optimization. Near fitness peaks, evolutionary trajectories are biased against greediness - from an optimization perspective, post-catastrophic selection is optimistic.

q-bio.PE↗

Learning functional groups in complex microbiomes

From soil to the gut, communities composed of thousands of microbes perform functions such as carbon sequestration and immune system regulation. Here, we introduce a data-driven approach that explains how community function can be traced to just a few groups of microbes or genes. In gut communities, our neural-network based clustering algorithm correctly recovers known functional groups. In the ocean metagenome, it distills ~500 gene modules down to three sparse groups highlighting survival strategies at different depths. In soils, it distills ~4400 bacterial species into two groups that enter a mathematical model of nitrate metabolism. By combining interpretable ML with strain isolation and sequencing experiments, we connect the metabolic specialization of each group to community-wide responses to perturbations. This integrated approach yields simple structure-function maps of microbiomes, allowing the discovery of molecular mechanisms underlying human and environmental health. More broadly, we illustrate how to do function-informed dimensionality reduction in biology.

physics.bio-ph↗

Inferring resource competition in microbial communities from time series

The competition for resources is a defining feature of microbial communities. In many contexts, from soils to host-associated communities, highly diverse microbes are organized into metabolic groups or guilds with similar resource preferences. The resource preferences of individual taxa that give rise to these guilds are critical for understanding fluxes of resources through the community and the structure of diversity in the system. However, inferring the metabolic capabilities of individual taxa, and their competition with other taxa, within a community is challenging and unresolved. Here we address this gap in knowledge by leveraging dynamic measurements of abundances in communities. We show that simple correlations are often misleading in predicting resource competition. We show that spectral methods such as the cross-power spectral density (CPSD) and coherence that account for time-delayed effects are superior metrics for inferring the structure of resource competition in communities. We first demonstrate this fact on synthetic data generated from consumer-resource models with time-dependent resource availability, where taxa are organized into groups or guilds with similar resource preferences. By applying spectral methods to oceanic plankton time-series data, we demonstrate that these methods detect interaction structures among species with similar genomic sequences. Our results indicate that analyzing temporal data across multiple timescales can reveal the underlying structure of resource competition within communities.

physics.soc-ph↗

An ensemble approach to the structure-function problem in microbial communities

The metabolic activity of microbes has played an essential role in the evolution and persistence of life on Earth. Microbial metabolism plays a primary role in the flow of carbon, nitrogen and other elements through the biosphere on a global scale. Microbes perform these metabolic activities in the context of complex communities comprised of many species that interact in dynamic and spatially-structured environments. Molecular genetics has revealed many of the metabolic pathways microbes utilize to generate energy and biomass. However, most of this knowledge is derived from model organisms, so we have a limited view of role of the massive genomic diversity in the wild on metabolic phenotypes. Further, we are only beginning to glimpse the principles governing how the metabolism of a community emerges from the collective action of its constituent members. As a result, one of the biggest challenges in the field is to understand how the metabolic activity of a community emerges from the genomic structure of the constituents. Here we propose an approach to this problem that rests on the quantitative analysis of metabolic activity in ensembles of microbial communities. We propose quantifying metabolic fluxes in diverse communities, either in the laboratory or the wild. We suggest that using sequencing data to quantify the genomic, taxonomic or transcriptional variation across an ensemble of communities can reveal low-dimensional descriptions of community structure that can explain or predict their emergent metabolic activity. We survey the types of communities for which this approach might be best suited and then review the analytical techniques available for quantifying metabolite dynamics in communities. Finally, we discuss what types of data analysis approaches might be lucrative for learning the structure-function mapping in communities from these data.

q-bio.PE↗

Biophysical constraints determine the selection of phenotypic fluctuations during directed evolution

Phenotypes of individuals in a population of organisms are not fixed. Phenotypic fluctuations, which describe temporal variation of the phenotype of an individual or individual-to-individual variation across a population, are present in populations from microbes to higher animals. Phenotypic fluctuations can provide a basis for adaptation and be the target of selection. Here we present a theoretical and experimental investigation of the fate of phenotypic fluctuations in directed evolution experiments where phenotypes are subject to constraints. We show that selecting bacterial populations for fast migration through a porous environment drives a reduction in cell-to-cell variation across the population. Using sequencing and genetic engineering we study the genetic basis for this reduction in phenotypic fluctuations. We study the generality of this reduction by developing a simple, abstracted, numerical simulation model of the evolution of phenotypic fluctuations subject to constraints. Using this model we find that strong and weak selection generally lead respectively to increasing or decreasing cell-to-cell variation as a result of a bound on the selected phenotype under a wide range of parameters. However, other behaviors are also possible, and we describe the outcome of selection simulations for different model parameters and suggest future experiments. We analyze the mechanism of the observed reduction of phenotypic fluctuations in our experimental system, discuss the relevance of our abstract model to the experiment and explore its broader implications for evolution.

q-bio.PE↗

Frequency and amplitude dependent population dynamics during cycles of feast and famine

In nature microbial populations are subject to fluctuating nutrient levels. Nutrient fluctuations are important for evolutionary and ecological dynamics in microbial communities since they impact growth rates, population sizes and biofilm formation. Here we use automated continuous-culture devices and high-throughput imaging to show that when populations of Escherichia coli are subjected to cycles of nutrient excess (feasts) and scarcity (famine) their abundance dynamics during famines depend on the frequency and amplitude of feasts. We show that frequency and amplitude dependent dynamics in planktonic populations arise from nutrient and history dependent rates of aggregation and dispersal. A phenomenological model recapitulates our experimental observations. Our results show that the statistical properties of environmental fluctuations have substantial impacts on spatial structure in bacterial populations driving large changes in abundance dynamics.

q-bio.PE↗