Ontology highlight
ABSTRACT:
PROVIDER: PRJEB38746 | ENA |
REPOSITORIES: ENA
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Project description:Characterization of the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here, we reconstruct the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. We find that the His3 fitness landscape is dominated by synergistic epistasis, such that the cumulative effect of amino acid substitutions causes a dramatic decline in fitness. Furthermore, in 63% of sites substitutions were strongly positive in one genetic background and strongly negative in another, with 41% of sites showing reciprocal sign epistasis. This sign epistasis, present in proportionally few genotypes, was caused by simultaneous interaction of multiple sites with demonstrating a complex multidimensional nature of the His3 fitness landscape.
2017-07-02 | GSE99990 | GEO
Project description:Adaptive laboratory evolution is highly effective for improving desired traits through natural selection. However, its applicability is inherently constrained to growth-correlated traits precluding traits of interest that incur a fitness cost, such as metabolite secretion. Here, we introduce the concept of tacking trait enabling natural selection of fitness-costly metabolic traits. The concept is inspired from the tacking maneuver used in sailing for traversing upwind. We use first-principle metabolic models to design an evolution niche wherein the tacking trait and fitness become correlated. Adaptive evolution in this niche, when followed by the reversal to the original niche, manifests in the improvement of the desired trait due to biochemical coupling between the tacking and the desired trait. We experimentally demonstrated this strategy, termed EvolveX, by evolving wine yeasts for increased aroma production. RNA-sequencing was performed for parental and evolved strains in the respective evolution niche and in natural grape must.
2021-12-30 | E-MTAB-10019 | biostudies-arrayexpress
Project description:RNA turnover is a primary source of gene expression variation, in turn promoting cellular adaptation. Mycobacteria leverage reversible mRNA stabilization to endure hostile conditions. Although ribonuclease E is essential for RNA turnover in several species, its role in mycobacterial single cell physiology and functional phenotypic diversification remains unexplored. Here, by integrating live-single-cell and quantitative-mass-spectrometry approaches, we show that ribonuclease E forms dynamic foci, which are associated with cellular homeostasis and single-cell fate, and we discover a versatile molecular interactome. We prove the interaction between ribonuclease E and the nucleoid-associated protein HupB, which is particularly pronounced during drug treatment and intracellularly, where we also observed marked increase of phenotypic diversity. Disruption of ribonuclease E expression affects HupB levels, impairing Mycobacterium tuberculosis growth homeostasis during treatment, intracellular replication and host spread. Our work lays the foundation for rational drug design against Mycobacterium tuberculosis diversification capacity, undermining its cellular balance and fitness landscape.
2022-03-25 | PXD025674 | Pride
Project description:Human activity is altering the environment at a rapid pace, challenging the adaptive capacities of genetic variation within animal populations. Animals also harbor extensive gut microbiomes, which play diverse roles in host health and fitness and may help expanding host capabilities. The unprecedented scale of human usage of xenobiotics and contamination with environmental toxins describes one challenge against which bacteria with their immense biochemical diversity are particularly suited to offer solutions. To explore the paths leading to bacteria-assisted rapid adaptation, we used Caenorhabditis elegans harboring a defined microbiome, and the antibiotic neomycin as a model toxin, harmful for the worm host and neutralized to different extents by microbiome members. Worms exposed to neomycin showed delayed development and decreased survival but were protected when colonized by neomycin-resistant members of the microbiome. Through a combination of 16S gene sequencing, counting of live bacteria and behavioral assays we identified two distinct mechanisms that facilitated adaptation: gut enrichment for a neomycin-modifying strain driven by altered bacterial competition; and host avoidance behavior, which depended on the stress-activated KGB-1/JNK and enabled preference of neomycin-protective bacteria. The straightforwardness of these mechanisms suggests that bacteria-assisted host adaptation may be more common than currently appreciated, protecting animals from novel stressors. However, gut remodeling may also cause dysbiosis, and additional experiments identified fitness trade-offs including increased susceptibility to infection as well as metabolic remodeling. Extending these results to other toxins suggests yet unaccounted-for microbiome-dependent long-term consequences of toxin exposure.
2023-11-09 | GSE246966 | GEO
Project description:Predicting and constraining RNA virus evolution require understanding the molecular factors that define the mutational landscape accessible to these pathogens. RNA viruses typically have high mutation rates, resulting in frequent production of protein variants with compromised biophysical properties. Their evolution is necessarily constrained by the consequent challenge to protein folding and function. We hypothesize that host proteostasis mechanisms, may be significant determinants of the fitness of viral protein variants, serving as a critical force shaping viral evolution. Here, we test this hypothesis by propagating influenza in host cells displaying chemically-controlled, divergent proteostasis environments. We find that both the nature of selection on the influenza genome and the accessibility of specific mutational trajectories are significantly impacted by host proteostasis. These findings provide new insights into features of host–pathogen interactions that shape viral evolution, and into the potential design of host proteostasis-targeted antiviral therapeutics that are refractory to resistance.
2017-11-15 | GSE102797 | GEO
Project description:Caloric restriction extends lifespan, an effect once thought to involve attenuation of reactive oxygen species (ROS) generated by aerobic metabolism. However, recent evidence suggests that caloric restriction may in fact raise ROS levels, which in turn provides protection from acute doses of oxidant through a process called adaptation. To shed light on the molecular mechanisms of adaptation, we designed a series of genome-wide deletion fitness screens to identify genes involved in adaptation to hydrogen peroxide.
2009-04-23 | GSE12733 | GEO
Project description:In some of the earliest uses of genome-wide gene-expression microarrays and array-based Comparative Genomic Hybridization (aCGH), a set of diploid yeasts that had undergone experimental evolution under aerobic glucose limitation was used to explore how gene expression and genome structure had responded to this selection pressure. To more deeply understand how adaptation to one environment might constrain or enhance performance in another we have now identified the adaptive mutations in this set of clones using whole-genome sequencing, and have assessed whether the evolved clones had become generalists or specialists by assaying their fitness under three contrasting growth environments: aerobic and anaerobic glucose limitation and aerobic acetate limitation. Additionally, evolved clones and their common ancestor were assayed for gene expression, biomass estimates and residual substrate levels under the alternative growth conditions. Relative fitnesses were evaluated by competing each clone against a common reference strain in each environment. Unexpectedly, we found that the evolved clones also outperformed their ancestor under strictly fermentative and strictly oxidative growth conditions. We conclude that yeasts evolving under aerobic glucose limitation become generalists for carbon limitation, as the mutations selected for in one environment are advantageous in others. High-throughput sequencing of the evolved clones uncovered mutations in genes involved in glucose sensing, signaling, and transport that in part explain these physiological phenotypes, with different sets of mutations found in independently-evolved clones. Earlier gene expression data from aerobic glucose-limited cultures had revealed a shift from fermentation towards respiration in all evolved clones explaining increased fitness in that condition. However, because the evolved clones also show higher fitness under strictly anaerobic conditions and under conditions requiring strictly respirative growth, this switch cannot be the sole source of adaptive benefit. Furthermore, because independently evolved clones are genetically distinct we conclude that there are multiple mutational paths leading to the generalist phenotype. Strain Name: Parental strain (CP1AB) or evolved clones (E1 - E5) Media: aerobic / anaerobic 36 hybridizations
2011-11-02 | E-GEOD-25081 | biostudies-arrayexpress
Project description:Escherichia coli Lrp regulates one-third of the genome via direct, cooperative, and indirect paths
| PRJNA438455 | ENA
Project description:In order to study the effects of a mutation to the transcriptional termination regulator Rho (referred to as rho*), we made use of expression microarrays to observe the direct and indirect effects of rho* on gene expression. In addition, we used arrays to map the fitness of strains from transposon mutagenized libraries under four conditions, showing that in each case the majority of genes with significant fitness effects were dependent on the genotype at rho.
2012-06-01 | GSE32022 | GEO