Massively parallel experimental interrogation of natural variants in ancient signaling pathways reveals both purifying selection and local adaptation.

The nature of standing genetic variation remains a central debate in population genetics, with differing perspectives on whether common variants are mostly neutral or have functional effects. We address this question by directly mapping the fitness effects of over 9,000 natural variants in the Ras/PKA and TOR/Sch9 pathways-key regulators of cell proliferation in eukaryotes-across four conditions in . While many variants are neutral in our assay, on the order of 3,500 exhibited significant fitness effects.

Global epistasis and the emergence of function in microbial consortia.

The many functions of microbial communities emerge from a complex web of interactions between organisms and their environment. This poses a significant obstacle to engineering microbial consortia, hindering our ability to harness the potential of microorganisms for biotechnological applications. In this study, we demonstrate that the collective effect of ecological interactions between microbes in a community can be captured by simple statistical models that predict how adding a new species to a community will affect its function.

Competition for shared resources increases dependence on initial population size during coalescence of gut microbial communities.

The long-term success of introduced populations depends on their initial size and ability to compete against existing residents, but it remains unclear how these factors collectively shape colonization. Here, we investigate how initial population (propagule) size and resource competition interact during community coalescence by systematically mixing eight pairs of microbial communities at ratios that vary over six orders of magnitude, and we compare our results to a neutral ecological model. Although the composition of the resulting co-cultures deviated substantially from neutral expectations, each co-culture contained species whose relative abundance depended on propagule size even after ~40 generations of growth.

Metabolic similarity and the predictability of microbial community assembly.

When microbial communities form, their composition is shaped by selective pressures imposed by the environment. Can we predict which communities will assemble under different environmental conditions? Here, we hypothesize that quantitative similarities in metabolic traits across metabolically similar environments lead to predictable similarities in community composition. To that end, we measured the growth rate and by-product profile of a library of proteobacterial strains in a large number of single nutrient environments.

The Architecture of Metabolic Networks Constrains the Evolution of Microbial Resource Hierarchies.

Microbial strategies for resource use are an essential determinant of their fitness in complex habitats. When facing environments with multiple nutrients, microbes often use them sequentially according to a preference hierarchy, resulting in well-known patterns of diauxic growth. In theory, the evolutionary diversification of metabolic hierarchies could represent a mechanism supporting coexistence and biodiversity by enabling temporal segregation of niches.

Predictability of the community-function landscape in wine yeast ecosystems.

Predictively linking taxonomic composition and quantitative ecosystem functions is a major aspiration in microbial ecology, which must be resolved if we wish to engineer microbial consortia. Here, we have addressed this open question for an ecological function of major biotechnological relevance: alcoholic fermentation in wine yeast communities. By exhaustively phenotyping an extensive collection of naturally occurring wine yeast strains, we find that most ecologically and industrially relevant traits exhibit phylogenetic signal, allowing functional traits in wine yeast communities to be predicted from taxonomy.

Emergent coexistence in multispecies microbial communities.

Understanding the mechanisms that maintain microbial biodiversity is a critical aspiration in ecology. Past work on microbial coexistence has largely focused on species pairs, but it is unclear whether pairwise coexistence in isolation is required for coexistence in a multispecies community. To address this question, we conducted hundreds of pairwise competition experiments among the stably coexisting members of 12 different enrichment communities in vitro.

The community-function landscape of microbial consortia.

Quantitatively linking the composition and function of microbial communities is a major aspiration of microbial ecology. Microbial community functions emerge from a complex web of molecular interactions between cells, which give rise to population-level interactions among strains and species. Incorporating this complexity into predictive models is highly challenging.

Assembly of gut-derived bacterial communities follows "early-bird" resource utilization dynamics.

Diet can impact host health through changes to the gut microbiota, yet we lack mechanistic understanding linking nutrient availability and microbiota composition. Here, we use thousands of microbial communities cultured from human feces to uncover simple assembly rules and develop a predictive model of community composition upon addition of single nutrients from central carbon metabolism to a complex medium. Community membership was largely determined by the donor feces, whereas relative abundances were determined by the supplemental carbon source.

Functional attractors in microbial community assembly.

For microbiome biology to become a more predictive science, we must identify which descriptive features of microbial communities are reproducible and predictable, which are not, and why. We address this question by experimentally studying parallelism and convergence in microbial community assembly in replicate glucose-limited habitats. Here, we show that the previously observed family-level convergence in these habitats reflects a reproducible metabolic organization, where the ratio of the dominant metabolic groups can be explained from a simple resource-partitioning model.

A metabolic modeling platform for the computation of microbial ecosystems in time and space (COMETS).

Genome-scale stoichiometric modeling of metabolism has become a standard systems biology tool for modeling cellular physiology and growth. Extensions of this approach are emerging as a valuable avenue for predicting, understanding and designing microbial communities. Computation of microbial ecosystems in time and space (COMETS) extends dynamic flux balance analysis to generate simulations of multiple microbial species in molecularly complex and spatially structured environments.

Engineering complex communities by directed evolution.

Directed evolution has been used for decades to engineer biological systems at or below the organismal level. Above the organismal level, a small number of studies have attempted to artificially select microbial ecosystems, with uneven and generally modest success. Our theoretical understanding of artificial ecosystem selection is limited, particularly for large assemblages of asexual organisms, and we know little about designing efficient methods to direct their evolution.

Nutrient dominance governs the assembly of microbial communities in mixed nutrient environments.

A major open question in microbial community ecology is whether we can predict how the components of a diet collectively determine the taxonomic composition of microbial communities. Motivated by this challenge, we investigate whether communities assembled in pairs of nutrients can be predicted from those assembled in every single nutrient alone. We find that although the null, naturally additive model generally predicts well the family-level community composition, there exist systematic deviations from the additive predictions that reflect generic patterns of nutrient dominance at the family level.

Complex yeast-bacteria interactions affect the yield of industrial ethanol fermentation.

Sugarcane ethanol fermentation represents a simple microbial community dominated by S. cerevisiae and co-occurring bacteria with a clearly defined functionality. In this study, we dissect the microbial interactions in sugarcane ethanol fermentation by combinatorically reconstituting every possible combination of species, comprising approximately 80% of the biodiversity in terms of relative abundance.

Directed Evolution of Microbial Communities.

Directed evolution is a form of artificial selection that has been used for decades to find biomolecules and organisms with new or enhanced functional traits. Directed evolution can be conceptualized as a guided exploration of the genotype-phenotype map, where genetic variants with desirable phenotypes are first selected and then mutagenized to search the genotype space for an even better mutant. In recent years, the idea of applying artificial selection to microbial communities has gained momentum.

Dissimilarity-Overlap analysis of replicate enrichment communities.

The taxonomic composition of microbial communities can vary substantially across habitats and within the same habitat over time. Efforts to build quantitative and predictive models of microbial population dynamics are underway, but fundamental questions remain. How different are population dynamics in different environments? Do communities that share the same taxa also exhibit identical dynamics? In vitro communities can help establish baseline expectations that are critical towards resolving these questions in natural communities.

Uncovering the rules of microbial community invasions.

Understanding the ecological and evolutionary processes determining the outcome of biological invasions has been the subject of decades of research with most work focusing on macro-organisms. In the context of microbes, invasions remain poorly understood despite being increasingly recognized as important. To shed light on the factors affecting the success of microbial community invasions, we perform simulations using an individual-based nearly neutral model that combines ecological and evolutionary processes.

On the deformability of an empirical fitness landscape by microbial evolution.

A fitness landscape is a map between the genotype and its reproductive success in a given environment. The topography of fitness landscapes largely governs adaptive dynamics, constraining evolutionary trajectories and the predictability of evolution. Theory suggests that this topography can be deformed by mutations that produce substantial changes to the environment.