Decoupling Environment-Dependent and Independent Genetic Robustness across Bacterial Species

The evolutionary origins of genetic robustness are still under debate: it may arise as a consequence of requirements imposed by varying environmental conditions, due to intrinsic factors such as metabolic requirements, or directly due to an adaptive selection in favor of genes that allow a species to endure genetic perturbations. Stratifying the individual effects of each origin requires one to study the pertaining evolutionary forces across many species under diverse conditions. Here we conduct the first large-scale computational study charting the level of robustness of metabolic networks of hundreds of bacterial species across many simulated growth environments. We provide evidence that variations among species in their level of robustness reflect ecological adaptations. We decouple metabolic robustness into two components and quantify the extents of each: the first, environmental-dependent, is responsible for at least 20% of the non-essential reactions and its extent is associated with the species' lifestyle (specialized/generalist); the second, environmental-independent, is associated (correlation = ∼0.6) with the intrinsic metabolic capacities of a species—higher robustness is observed in fast growers or in organisms with an extensive production of secondary metabolites. Finally, we identify reactions that are uniquely susceptible to perturbations in human pathogens, potentially serving as novel drug-targets

Biological Robustness: Paradigms, Mechanisms, and Systems Principles

Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior

Synthetic biology: advancing biological frontiers by building synthetic systems

Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field

Dispensability of Escherichia coli's latent pathways

Gene-knockout experiments on single-cell organisms have established that expression of a substantial fraction of genes is not needed for optimal growth. This problem acquired a new dimension with the recent discovery that environmental and genetic perturbations of the bacterium Escherichia coli are followed by the temporary activation of a large number of latent metabolic pathways, which suggests the hypothesis that temporarily activated reactions impact growth and hence facilitate adaptation in the presence of perturbations. Here we test this hypothesis computationally and find, surprisingly, that the availability of latent pathways consistently offers no growth advantage, and tends in fact to inhibit growth after genetic perturbations. This is shown to be true even for latent pathways with a known function in alternate conditions, thus extending the significance of this adverse effect beyond apparently nonessential genes. These findings raise the possibility that latent pathway activation is in fact derivative of another, potentially suboptimal, adaptive response

Broad-Host-Range Genetic Tools for Observing Microbial Consortia

Microbial communities are complex assemblages that are key to ecosystem stability and human health. Synthetic ecology aims to design and construct microbial consortia with reduced complexity that enable innovative applications beyond monocultures. However, their robust and performance-based design is constrained by limited knowledge of growth dynamics and derived binary interactions that are critical for community functioning. Decoupling population dynamics and inferring interspecies interactions from strain-specific fitness data remains a major challenge due to the difficulty of monitoring and quantifying species-specific growth in mixed microbial communities. Existing methods have the disadvantage that they are not suitable for fast, scalable, high throughput applications such as those needed at the interface between synthetic biology and microbial ecology, where the screening of large design spaces associated with the construction and observation of synthetic co-cultures is required. In this thesis, a standardized platform functioning as a tractable tool for the interrogation of population dynamics based on measurements of strain-specific fluorescence in microbial co-cultures was developed. This was accomplished by constructing a set of broad-host-range plasmids in the BASIC environment that constitutively express fluorescent reporter proteins and estimating the ecological fitness of species in terms of specific growth rate (µ) and carrying capacity (K) from static and time-course optical density and fluorescence measurements through regression analysis of bacterial growth models. Experimental investigation of model binary co-cultures constructed from six model and non-traditional bacterial hosts demonstrated successful decoupling of population dynamics and inference of interspecies interactions in 96-well plates based on fluorescence. Furthermore, the results emphasize the need for the right choice of genetic tools for a meaningful interrogation of co-culture dynamics and inference of interactions, consistent with the finding that the suitability of fluorescence as a surrogate for bacterial biomass depends on the combination of host species and fluorescent protein. It is anticipated that this toolkit can contribute to applications in synthetic microbial ecology and biotechnology by providing a flexible, scalable, and reproducible approach to decouple populations dynamics in synthetic co-cultures

Influence of Climate Change on Obligatory Interactions in the Ecosystem: Predicting the Future

Obligatory interactions in the ecosystem are sensitive to climate fluctuations. The study of how   mutualistic and parasitic associations which are obligatory for the partners, respond to past climate change especially in the Quaternary, would help deepen the understanding and provide clues to how ecosystems would respond to current and future climate changes. Data was obtained by searching through articles from different scientific databases spanning from 1990 to 2022.  The focus was on decoupling of partners, changes of the distributional limits of partner species and response to sudden climate change by the interacting partner species. From this review, data on response of obligate interactions to past climate change is limited and all constraints should be removed to allow for sufficient and appropriate data. Efficient calibration of demographic events from genetic data coupled with use of suitable biological models; including enhanced number of models from the tropics to help resolve the difficulty of timing biological events may be the way forward. Keywords: obligate; interactions; Quaternary; climate change; ecosystem: DOI: 10.7176/JEES/13-5-04 Publication date:July 31st 202

Independent evolution of shape and motility allows evolutionary flexibility in Firmicutes bacteria

Functional morphological adaptation is an implicit assumption across many ecological studies. However, despite a few pioneering attempts to link bacterial form and function, functional morphology is largely unstudied in prokaryotes. One intriguing candidate for analysis is bacterial shape, as multiple lines of theory indicate that cell shape and motility should be strongly correlated. Here we present a large-scale use of modern phylogenetic comparative methods to explore this relationship across 325 species of the phylum Firmicutes. In contrast to clear predictions from theory, we show that cell shape and motility are not coupled, and that transitions to and from flagellar motility are common and strongly associated with lifestyle (free-living or host-associated). We find no association between shape and lifestyle, and contrary to recent evidence, no indication that shape is associated with pathogenicity. Our results suggest that the independent evolution of shape and motility in this group might allow a greater evolutionary flexibility

Auxotrophic interactions: A stabilizing attribute of aquatic microbial communities?

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Johnson, W. M., Alexander, H., Bier, R. L., Miller, D. R., Muscarella, M. E., Pitz, K. J., & Smith, H. Auxotrophic interactions: A stabilizing attribute of aquatic microbial communities? FEMS Microbiology Ecology, (2020): fiaa115, doi: 10.1093/femsec/fiaa115.Auxotrophy, or an organism's requirement for an exogenous source of an organic molecule, is widespread throughout species and ecosystems. Auxotrophy can result in obligate interactions between organisms, influencing ecosystem structure and community composition. We explore how auxotrophy-induced interactions between aquatic microorganisms affect microbial community structure and stability. While some studies have documented auxotrophy in aquatic microorganisms, these studies are not widespread, and we therefore do not know the full extent of auxotrophic interactions in aquatic environments. Current theoretical and experimental work suggests that auxotrophy links microbial community members through a complex web of metabolic dependencies. We discuss the proposed ways in which auxotrophy may enhance or undermine the stability of aquatic microbial communities, highlighting areas where our limited understanding of these interactions prevents us from being able to predict the ecological implications of auxotrophy. Finally, we examine an example of auxotrophy in harmful algal blooms to place this often theoretical discussion in a field context where auxotrophy may have implications for the development and robustness of algal bloom communities. We seek to draw attention to the relationship between auxotrophy and community stability in an effort to encourage further field and theoretical work that explores the underlying principles of microbial interactions.This work was supported by the National Science Foundation [OCE-1356192]

The compositional and evolutionary logic of metabolism

Metabolism displays striking and robust regularities in the forms of modularity and hierarchy, whose composition may be compactly described. This renders metabolic architecture comprehensible as a system, and suggests the order in which layers of that system emerged. Metabolism also serves as the foundation in other hierarchies, at least up to cellular integration including bioenergetics and molecular replication, and trophic ecology. The recapitulation of patterns first seen in metabolism, in these higher levels, suggests metabolism as a source of causation or constraint on many forms of organization in the biosphere. We identify as modules widely reused subsets of chemicals, reactions, or functions, each with a conserved internal structure. At the small molecule substrate level, module boundaries are generally associated with the most complex reaction mechanisms and the most conserved enzymes. Cofactors form a structurally and functionally distinctive control layer over the small-molecule substrate. Complex cofactors are often used at module boundaries of the substrate level, while simpler ones participate in widely used reactions. Cofactor functions thus act as "keys" that incorporate classes of organic reactions within biochemistry. The same modules that organize the compositional diversity of metabolism are argued to have governed long-term evolution. Early evolution of core metabolism, especially carbon-fixation, appears to have required few innovations among a small number of conserved modules, to produce adaptations to simple biogeochemical changes of environment. We demonstrate these features of metabolism at several levels of hierarchy, beginning with the small-molecule substrate and network architecture, continuing with cofactors and key conserved reactions, and culminating in the aggregation of multiple diverse physical and biochemical processes in cells.Comment: 56 pages, 28 figure