Cycling in Simple Genetic Systems: II. The Symmetric Cases

Author(s):  
E. Akin
Keyword(s):  
2015 ◽  
Vol 41 (1) ◽  
pp. 57
Author(s):  
Juan WEN ◽  
Jian-Feng XU ◽  
Yan LONG ◽  
Hai-Ming XU ◽  
Jin-Ling MENG ◽  
...  

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 271
Author(s):  
Chentao Yong ◽  
Andras Gyorgy

While the vision of synthetic biology is to create complex genetic systems in a rational fashion, system-level behaviors are often perplexing due to the context-dependent dynamics of modules. One major source of context-dependence emerges due to the limited availability of shared resources, coupling the behavior of disconnected components. Motivated by the ubiquitous role of toggle switches in genetic circuits ranging from controlling cell fate differentiation to optimizing cellular performance, here we reveal how their fundamental dynamic properties are affected by competition for scarce resources. Combining a mechanistic model with nullcline-based stability analysis and potential landscape-based robustness analysis, we uncover not only the detrimental impacts of resource competition, but also how the unbalancedness of the switch further exacerbates them. While in general both of these factors undermine the performance of the switch (by pushing the dynamics toward monostability and increased sensitivity to noise), we also demonstrate that some of the unwanted effects can be alleviated by strategically optimized resource competition. Our results provide explicit guidelines for the context-aware rational design of toggle switches to mitigate our reliance on lengthy and expensive trial-and-error processes, and can be seamlessly integrated into the computer-aided synthesis of complex genetic systems.


Genetics ◽  
1998 ◽  
Vol 148 (3) ◽  
pp. 1333-1340 ◽  
Author(s):  
Hong-Wen Deng ◽  
Yun-Xin Fu

AbstractThe past decades have witnessed extensive efforts to correlate fitness traits with genomic heterozygosity. While positive correlations are revealed in most of the organisms studied, results of no/negative correlations are not uncommon. There has been little effort to reveal the genetic causes of these negative correlations. The positive correlations are regarded either as evidence for functional overdominance in large, randomly mating populations at equilibrium, or the results of populations at disequilibrium under dominance. More often, the positive correlations are viewed as a phenomenon of heterosis, so that it cannot possibly occur under within-locus additive allelic effects. Here we give exact genetic conditions that give rise to positive and negative correlations in populations at Hardy-Weinberg and linkage equilibria, thus offering a genetic explanation for the observed negative correlations. Our results demonstrate that the above interpretations concerning the positive correlations are not complete or even necessary. Such a positive correlation can result under dominance and potentially under additivity, even in populations where associated overdominance due to linked alleles at different loci is not significant. Additionally, negative correlations and heterosis can co-occur in a single population. Although our emphasis is on equilibrium populations and for biallelic genetic systems, the basic conclusions are generalized to non-equilibrium populations and for multi-allelic situations.


2021 ◽  
pp. 2000252
Author(s):  
Yang Zhang ◽  
Wentao Ding ◽  
Zhihui Wang ◽  
Huimin Zhao ◽  
Shuobo Shi

1993 ◽  
Vol 9 (10) ◽  
pp. 392-395 ◽  
Author(s):  
L.D. Sibley ◽  
E.R. Pfefferkorn ◽  
J.C. Boothroyd

1977 ◽  
Vol 26 (1) ◽  
pp. 81-82 ◽  
Author(s):  
Steve Selvin

A definition of efficiency is presented to aid a researcher in the choice of the genetic systems for the diagnosis of twin zygosity. An expression is given that produces a numeric value that indicates which systems do the most effective job of discriminating DZ twins from a sample of twin pairs. This definition of efficiency is illustrated with eight blood groups commonly used in twin zygosity diagnosis.


2017 ◽  
Author(s):  
Olivier Borkowski ◽  
Drew Endy ◽  
Pakpoom Subsoontorn

AbstractBackgroundAutonomous cell-based control of heterologous gene expression can simplify batch-culture bioprocessing by eliminating external monitoring and extrinsic control of culture conditions. Existing approaches use auto-induction media, synthetic cell-cell communication systems, or application-specific biosensors. A simpler, resource-efficient, and general-purpose expression control system responsive to common changes during batch culture would be useful.ResultsWe used nativeE.colipromoters and recombinase-based switches to repurpose endogenous transcription signals for control of heterologous gene expression. Specifically, natural changes in transcription from endogenous promoters result in recombinase expression at different phases of batch culture. So-expressed recombinases invert a constitutive promoter regulating expression of arbitrary heterologous genes. We realized reversible and single-use switching, reduced static and dynamic cell-to-cell variation, and overall expression amplification. We used “off-the-shelf” genetic parts and abstraction-based composition frameworks to realize reliable forward engineering of our synthetic genetic systems.ConclusionWe engineered autonomous control systems for regulating heterologous gene expression. Our system uses generic endogenous promoters to sense and control heterologous expression during growth-phase transitions. Our system does not require specialized auto-induction media, production or activation of quorum sensing, or the development of application-specific biosensors. Cells programmed to control themselves could simplify existing bioprocess operations and enable the development of more powerful synthetic genetic systems.


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