SEARCH · PubMed Health

Results for “bistability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

8 recordsLinked to original sources

PubMed2025

Bistable Mutation-Selection Equilibria and Violations of Fisher's Theorem in Tetraploids: Insights from Nonlinear Dynamics.

Polyploidy and whole genome duplication (WGD) are widespread biological phenomena with substantial cellular, meiotic, and genetic effects. Despite their prevalence and significance across the tree of life, population genetics theory for polyploids is not well developed. The lack of theoretical models limits our understanding of polyploid evolution and restricts our ability to harness polyploidy for crop improvement amidst increasing environmental stress. To address this gap, we developed and analyzed deterministic models of mutation-selection balance for tetraploids under polysomic (autotetraploid) and disomic (allotetraploid) inheritance patterns and arbitrary dominance relationships. We also introduced a new mathematical framework based on ordinary differential equations and nonlinear dynamics for analyzing the models. We find that autotetraploids approach Hardy-Weinberg Equilibrium 33% faster than allotetraploids, but the different tetraploid inheritance models show little differences in mutation load and allele frequency at mutation-selection balance. Our model also reveals two bistable points of mutation-selection balance for dominant alleles with biased mutation rates over a wide range of selection coefficients in the tetraploid models compared to bistability in only a narrow range for diploids. Finally, using discrete time simulations, we explore the temporal dynamics of allele frequency and fitness change and compare these dynamics to the predictions of Fisher's Fundamental Theorem of Natural Selection. While Fisher's predictions generally hold, we show that the bistable dynamics for dominant mutations fundamentally alter the associated temporal dynamics. Overall, this work develops foundational theoretical models that will facilitate the development of population genetic models and methodologies to study evolution in empirical tetraploid populations.

Fisher’s Fundamental Theorem↗

PubMed1977

[Bistability in the activity of glutamine synthetase in ammonium-limiting chemostat cultures of Escherichia coli ML 30].

The approximative estimation of the function micron([NH+4]) in cultures of E. coli ML 30 had shown that bistability of the ammonium concentration in ammonium limited continuous cultures could be possible (BERGTER et al. 1977). This phenomenon suggested a bistability in the regulation of ammonia assimilation. Therefore, the activity of one key enzyme of the two ammonia assimilation systems was measured. The distribution of the activity of glutamine synthetase in ammonia limited continuous cultures after different transition states confirmed this suggestion.

Ammonia↗

PubMed1979

[All-or-none behaviour and bistability in a simple cell model with autocatalysis of type A+2B = 3B (author's transl)].

Nonlinear kinetics in a chemical cell model involving only one substrate (A) and one product (B), two reactions (A yields B and A + 2B yields OB), and passive diffusion of A and B through the cell wall, can exhibit complex behaviour including oscillations, bistability (switching) and spiking. One such system is presented, which shows three kinds of response as depending on the quantity of a stimulus--a sudden imput of product B: i. no response; ii, spiking; iii, switching into an alternative steady state--i.e. an "all-or flip-or-none" response.

Animals↗

PubMed2025

Nrm1 is a bistable switch connecting cell cycle progression to transcriptional control.

Entry into the cell cycle requires activation of G1 cyclin-dependent kinases (CDKs) and the G1/S transcriptional program. In fission yeast, the MBF complex is the main transcription factor driving early cell-cycle gene expression. MBF-dependent transcription is activated in metaphase and repressed at the end of S phase by a feedback loop involving the cyclin Cig2 and co-repressors Nrm1 and Yox1. While replicative stress inactivates Yox1 via phosphorylation, the mechanism that activates MBF during an unperturbed cell cycle remains unclear. Here, we identify Nrm1 as the key target of cell cycle regulation in a two-step control mechanism. First, CDK1 phosphorylates Nrm1 in metaphase, leading to its release-along with Yox1-from chromatin. Second, unphosphorylated Nrm1, generated either by dephosphorylation or de novo synthesis, is degraded during anaphase, preventing its re-association with MBF until the end of the next S phase. Together, these parallel pathways create a precisely timed window of MBF activation, ensuring proper cell cycle progression and preserving genomic stability.

Schizosaccharomyces↗

PubMed2026

Kinetic model of E-P condensates dynamics reveals transcriptional speed, noise, and energy trade-offs.

Gene regulation emerges from the interplay between chromatin architecture and the molecular interactions that connect enhancers to promoters. To study how these interactions shape transcriptional dynamics, we developed a kinetic model that incorporates multivalent enhancer-promoter binding, transcription factor competition, steric constraints, and chromatin accessibility. The model shows that competition among regulatory factors can generate bistable promoter states at the expense of increased transcriptional noise, revealing a direct relationship between bistability and noise levels. It further predicts that promoter response times are fastest in parameter regimes where bistability appears, suggesting that regulatory dynamics supporting two promoter states may intrinsically enable rapid activation. Extending this analysis, we find that intermediate chromatin accessibility and competition between activators and repressors both promote bistable enhancer-bound promoter clusters and fast switching at the cost of higher noise, whereas very high or low accessibility and noncompetitive transcription factors result in monostable expression states. The model also offers a quantitative framework to compare the energetic costs of different regulatory strategies, indicating that, under energy constraints, cells may favor adjusting transcription factor concentrations rather than altering chromatin accessibility, thereby linking energy expenditure to regulatory flexibility and robustness.

Kinetics↗

PubMed2026

The value of a prophage-borne defense system in phage-phage competition.

Temperate phages that incorporate into their bacterial hosts' genomes often encode defense systems that protect their hosts from superinfection by unrelated phages. Yet the evolutionary value of such defenses to the phage remains unclear. We present a minimal theoretical framework to quantify the selective advantage of a prophage-borne defense system in competition between temperate phages infecting the same bacterial host. The model reveals regimes in which a "defensive phage" can invade and persist despite growth costs, regimes of bistability, and others in which all phage types coexist due to a rock-paper-scissors-like dynamic between defensive, non-defensive, and defense-loss variants. Because defense systems can be non-transitive, true rock-paper-scissors relations can lead to persistent oscillations. These results identify simple conditions under which phage-encoded defense systems are evolutionarily stable, providing testable predictions for the prevalence and maintenance of these systems in natural microbial communities.

Prophages↗

PubMed2025

The SinR·SlrR Heteromer Attenuates Transcription of a Long Operon of Flagellar Genes in Bacillus subtilis.

During growth, Bacillus subtilis differentiates into subpopulations of motile individuals and non-motile chains, associated with dispersal and biofilm formation, respectively. The two cell types are dictated by the activity of the alternative sigma factor SigD encoded as the penultimate gene of the 27-kb long fla/che flagellar operon. The frequency of SigD-ON motile cells is increased by the heteromeric transcription factor SwrA·DegU that activates the fla/che promoter. Conversely, the frequency of motile cells is decreased by the heteromeric transcription factor SinR·SlrR, but the mechanism and location of inhibition is poorly understood. Here, using ChIP-Seq analysis, we determine the binding sites of the SinR·SlrR heteromer on the genome. We identified two sites within the fla/che operon that were necessary and sufficient to attenuate transcript abundance by causing premature termination upstream of the gene that encodes SigD. Thus, cell motility and the transition to biofilm formation depend on the expression of a long operon governed by two opposing heteromeric transcription factors that operate at two different stages of the transcription cycle. More broadly, our study serves as a model for transcription factors that control transcriptional elongation and the regulation of long operons in bacteria.

Bacillus subtilis↗

PubMed2025

100+ years of phase variation: the premier bacterial bet-hedging phenomenon.

Stochastic, reversible switches in the expression of Salmonella flagella variants were first described by Andrewes in 1922. Termed phase variation (PV), subsequent research found that this phenomenon was widespread among bacterial species and controlled expression of major determinants of bacterial-host interactions. Underlying mechanisms were not discovered until the 1970s/1980s but were found to encompass intrinsic aspects of DNA processes (i.e. DNA slippage and recombination) and DNA modifications (i.e. DNA methylation). Despite this long history, discoveries are ongoing with expansions of the phase-variable repertoire into new organisms and novel insights into the functions of known loci and switching mechanisms. Some of these discoveries are somewhat controversial as the term 'PV' is being applied without addressing key aspects of the phenomenon such as whether mutations or epigenetic changes are reversible and generated prior to selection. Another 'missing' aspect of PV research is the impact of these adaptive switches in real-world situations. This review provides a perspective on the historical timeline of the discovery of PV, the current state-of-the-art, controversial aspects of classifying phase-variable loci and possible 'missing' real-world effects of this phenomenon.

Gene Expression Regulation, Bacterial↗