The microbiota is generally assumed to have a substantial influence on the biology of multicellular organisms. The exact functional contributions of the microbes are often unclear and cannot be inferred easily from 16S rRNA genotyping, which is commonly used for taxonomic characterization of bacterial associates. In order to bridge this knowledge gap, we here analyzed the metabolic competences of the native microbiota of the model nematode Caenorhabditis elegans. We integrated wholegenome sequences of 77 bacterial microbiota members with metabolic modeling and experimental characterization of bacterial physiology. We found that, as a community, the microbiota can synthesize all essential nutrients for C. elegans. Both metabolic models and experimental analyses revealed that nutrient context can influence how bacteria interact within the microbiota. We identified key bacterial traits that are likely to influence the microbe's ability to colonize C. elegans (i.e., the ability of bacteria for pyruvate fermentation to acetoin) and affect nematode fitness (i.e., bacterial competence for hydroxyproline degradation). Considering that the microbiota is usually neglected in C. elegans research, the resource presented here will help our understanding of this nematode's biology in a more natural context. Our integrative approach moreover provides a novel, general framework to characterize microbiota-mediated functions.
Conventionally, neuronal development is regarded to follow a stereotypic sequence of neurogenesis, migration, and differentiation. We demonstrate that this notion is not a general principle of neuronal development by documenting the timing of mitosis in relation to multiple differentiation events for bipolar cells (BCs) in the zebrafish retina using in vivo imaging. We found that BC progenitors undergo terminal neurogenic divisions while in markedly disparate stages of neuronal differentiation. Remarkably, the differentiation state of individual BC progenitors at mitosis is not arbitrary but matches the differentiation state of post‐mitotic BCs in their surround. By experimentally shifting the relative timing of progenitor division and differentiation, we provide evidence that neurogenesis and differentiation can occur independently of each other. We propose that the uncoupling of neurogenesis and differentiation could provide neurogenic programs with flexibility, while allowing for synchronous neuronal development within a continuously expanding cell pool.
The concept of fitness is often reduced to a single component, such as the replication rate in a given habitat. For species with multi-step life cycles, this can be an unjustified oversimplification, as every step of the life cycle can contribute to the overall reproductive success in a specific way. In particular, this applies to microbes that spend part of their life cycles associated to a host. In this case, there is a selection pressure not only on the replication rates, but also on the phenotypic traits associated to migrating from the external environment to the host and vice-versa (i.e., the migration rates). Here, we investigate a simple model of a microbial lineage living, replicating, migrating and competing in and between two compartments: a host and an environment. We perform a sensitivity analysis on the overall growth rate to determine the selection gradient experienced by the microbial lineage. We focus on the direction of selection at each point of the phenotypic space, defining an optimal way for the microbial lineage to increase its fitness. We show that microbes can adapt to the two-compartment life cycle through either changes in replication or migration rates, depending on the initial values of the traits, the initial distribution across the two compartments, the intensity of competition, and the time scales involved in the life cycle versus the time scale of adaptation (which determines the adequate probing time to measure fitness). Overall, our model provides a conceptual framework to study the selection on microbes experiencing a host-associated life cycle.
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