The fixation probability of rare mutators in finite asexual populations

A mutator is an allele that increases the mutation rate throughout the genome by disrupting some aspect of DNA replication or repair. Mutators that increase the mutation rate by the order of 100 fold have been observed to spontaneously emerge and achieve high frequencies in natural populations and in long-term laboratory evolution experiments with \textit{E. coli}. In principle, the fixation of mutator alleles is limited by (i) competition with mutations in wild-type backgrounds, (ii) additional deleterious mutational load, and (iii) random genetic drift. Using a multiple locus model and employing both simulation and analytic methods, we investigate the effects of these three factors on the fixation probability $P_{fix}$ of an initially rare mutator as a function of population size $N$, beneficial and deleterious mutation rates, and the strength of mutations $s$. Our diffusion based approximation for $P_{fix}$ successfully captures effects (ii) and (iii) when selection is fast compared to mutation ($\mu/s \ll 1$). This enables us to predict the conditions under which mutators will be evolutionarily favored. Surprisingly, our simulations show that effect (i) is typically small for strong-effect mutators. Our results agree semi-quantitatively with existing laboratory evolution experiments and suggest future experimental directions.Comment: 46 pages, 8 figure

Birth and Death of One-dimensional Domains in Cylindrically Confined Liquid Crystals

Nematic liquid crystal (LC) is a partially ordered matter that has been a popular model system for studying a variety of topological behaviors in condensed matter. In this work, utilizing a spontaneously twisting achiral LC, we introduce a one-dimensional (1D) model system to investigate how domains and topological defects arise and annihilate, reminiscing the Kibble-Zurek mechanism. Because of the unusual elastic properties, lyotropic chromonic LCs form a double-twist structure in a cylindrical capillary with degenerate planar anchoring, exhibiting chiral symmetry breaking despite the absence of intrinsic chirality. Consequently, the domains of different handedness coexist with equal probabilities, forming the topological defects between them. We experimentally measure the domain-length distribution and its time evolution, best fitted by a three-parameter log-normal distribution. We propose that the coalescence within a train of 1D domains having the normal length distribution and randomly assigned handedness, may lead to the domains of the log-normal-like length distribution. Our cylindrically confined LC provides a practical model system to study the formation and annihilation of domains and defects in 1D

Rewiring carbon catabolite repression for microbial cell factory

Carbon catabolite repression (CCR) is a key regulatory system found in most microorganisms that ensures preferential utilization of energy-efficient carbon sources. CCR helps microorganisms obtain a proper balance between their metabolic capacity and the maximum sugar uptake capability. It also constrains the deregulated utilization of a preferred cognate substrate, enabling microorganisms to survive and dominate in natural environments. On the other side of the same coin lies the tenacious bottleneck in microbial production of bioproducts that employs a combination of carbon sources in varied proportion, such as lignocellulose-derived sugar mixtures. Preferential sugar uptake combined with the transcriptional and/or enzymatic exclusion of less preferred sugars turns out one of the major barriers in increasing the yield and productivity of fermentation process. Accumulation of the unused substrate also complicates the downstream processes used to extract the desired product. To overcome this difficulty and to develop tailor-made strains for specific metabolic engineering goals, quantitative and systemic understanding of the molecular interaction map behind CCR is a prerequisite. Here we comparatively review the universal and strain-specific features of CCR circuitry and discuss the recent efforts in developing synthetic cell factories devoid of CCR particularly for lignocellulose-based biorefinery.close11

The art of reporter proteins in science: past, present and future applications

Starting with the first publication of lacZ gene fusion in 1980, reporter genes have just entered their fourth decade. Initial studies relied on the simple fusion of a promoter or gene with a particular reporter gene of interest. Such constructs were then used to determine the promoter activity under specific conditions or within a given cell or organ. Although this protocol was, and still is, very effective, current research shows a paradigm shift has occurred in the use of reporter systems. With the advent of innovative cloning and synthetic biology techniques and microfluidic/nanodroplet systems, reporter genes and their proteins are now finding themselves used in increasingly intricate and novel applications. For example, researchers have used fluorescent proteins to study biofilm formation and discovered that microchannels develop within the biofilm. Furthermore, there has recently been a "fusion" of art and science; through the construction of genetic circuits and regulatory systems, researchers are using bacteria to "paint" pictures based upon external stimuli. As such, this review will discuss the past and current trends in reporter gene applications as well as some exciting potential applications and models that are being developed based upon these remarkable proteinsclose222

Microbial linguistics: perspectives and applications of microbial cell-to-cell communication

Inter-cellular communication via diffusible small molecules is a defining character not only of multicellular forms of life but also of single-celled organisms. A large number of bacterial genes are regulated by the change of chemical milieu mediated by the local population density of its own species or others. The cell density-dependent "autoinducer" molecules regulate the expression of those genes involved in genetic competence, biofilm formation and persistence, virulence, sporulation, bioluminescence, antibiotic production, and many others. Recent innovations in recombinant DNA technology and micro-/nano-fluidics systems render the genetic circuitry responsible for cell-to-cell communication feasible to and malleable via synthetic biological approaches. Here we review the current understanding of the molecular biology of bacterial intercellular communication and the novel experimental protocols and platforms used to investigate this phenomenon. A particular emphasis is given to the genetic regulatory circuits that provide the standard building blocks which constitute the syntax of the biochemical communication network Thus, this review gives focus to the engineering principles necessary for rewiring bacterial chemo-communication for various applications, ranging from population-level gene expression control to the study of host-pathogen interactions.close0

The Boltzmann fair division for distributive justice

Fair division is a significant, long-standing problem and is closely related to social and economic justice. The conventional division methods such as cut-and-choose are hardly applicable to real-world problems because of their complexity and unrealistic assumptions about human behaviors. Here we propose a fair division method from a completely different perspective, using the Boltzmann division. The mathematical model of the Boltzmann division was developed for both homogeneous and heterogeneous cake-cutting problems, and the realistic human factors (contributions, needs, and preferences) of the multiple participating players could be successfully integrated. The Boltzmann division was then optimized by maximizing the players' total utility. We show that the Boltzmann fair division is a division method favorable to the socially disadvantaged or underprivileged, and it is drastically simple yet highly versatile and can be easily fine-tuned to directly apply to a variety of social, economic, and political division problems

The Boltzmann fair division for distributive justice

Fair division is a significant, long-standing problem and is closely related to social and economic justice. The conventional division methods such as cut-and-choose are hardly applicable to real-world problems because of their complexity and unrealistic assumptions about human behaviors. Here we propose a fair division method from a completely different perspective, using the Boltzmann division. The mathematical model of the Boltzmann division was developed for both homogeneous and heterogeneous cake-cutting problems, and the realistic human factors (contributions, needs, and preferences) of the multiple participating players could be successfully integrated. The Boltzmann division was then optimized by maximizing the players' total utility. We show that the Boltzmann fair division is a division method favorable to the socially disadvantaged or underprivileged, and it is drastically simple yet highly versatile and can be easily fine-tuned to directly apply to a variety of social, economic, and political division problems

Cost-effective circadian mechanism: rhythmic degradation of circadian proteins spontaneously emerges without rhythmic post-translational regulation

Circadian protein oscillations are maintained by the lifelong repetition of protein production and degradation in daily balance. It comes at the cost of ever-replayed, futile protein synthesis each day. This biosynthetic cost with a given oscillatory protein profile is relievable by a rhythmic, not constant, degradation rate that selectively peaks at the right time of day but remains low elsewhere, saving much of the gross protein loss and of the replenishing protein synthesis. Here, our mathematical modeling reveals that the rhythmic degradation rate of proteins with circadian production spontaneously emerges under steady and limited activity of proteolytic mediators and does not necessarily require rhythmic post-translational regulation of previous focus. Additional (yet steady) post-translational modifications in a proteolytic pathway can further facilitate the degradation's rhythmicity in favor of the biosynthetic cost saving. Our work is supported by animal and plant circadian data, offering a generic mechanism for potentially widespread, time-dependent protein turnover

Kinetic roughening of ion-sputtered Pd(001) surface: Beyond the Kuramoto-Sivashinsky model

The kinetic roughening of Ar+ ion-sputtered Pd(001) surface was investigated. The facet formation on the sputtered surface was studied by tracing the extradiffraction peaks or satellites around the diffraction peaks corresponding to the sample surface. The morphological evolution of the sputtered Pd(001) surface was also investigated by an scanning tunneling microscopy (STM). It was shown that the nanoscale adatom islands form and grow with increasing sputter time.open313

Large-scale metabolic interaction network of the mouse and human gut microbiota

The role of our gut microbiota in health and disease is largely attributed to the collective metabolic activities of the inhabitant microbes. A system-level framework of the microbial community structure, mediated through metabolite transport, would provide important insights into the complex microbe-microbe and host-microbe chemical interactions. This framework, if adaptable to both mouse and human systems, would be useful for mechanistic interpretations of the vast amounts of experimental data from gut microbiomes in murine animal models, whether humanized or not. Here, we constructed a literature-curated, interspecies network of the mammalian gut microbiota for mouse and human hosts, called NJC19. This network is an extensive data resource, encompassing 838 microbial species (766 bacteria, 53 archaea, and 19 eukaryotes) and 6 host cell types, interacting through 8,224 small-molecule transport and macromolecule degradation events. Moreover, we compiled 912 negative associations between organisms and metabolic compounds that are not transportable or degradable by those organisms. Our network may facilitate experimental and computational endeavors for the mechanistic investigations of host-associated microbial communities