Noise in gene expression: origins, consequences, and control

Genetically identical cells and organisms exhibit remarkable diversity even when they have identical histories of environmental exposure. Noise, or variation, in the process of gene expression may contribute to this phenotypic variability. Recent studies suggest that this noise has multiple sources, including the stochastic or inherently random nature of the biochemical reactions of gene expression. In this review, we summarize noise terminology and comment on recent investigations into the sources, consequences, and control of noise in gene expression.     

Using gene expression noise to understand gene regulation

Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a major source of this variability, and its physiological consequences have been topics of intense research for the last decade. Several recent studies have measured variability in protein and messenger RNA levels, and they have discovered strong connections between noise and gene regulation mechanisms. When integrated with discrete stochastic models, measurements of cell-to-cell variability provide a sensitive "fingerprint" with which to explore fundamental questions of gene regulation. In this review, we highlight several studies that used gene expression variability to develop a quantitative understanding of the mechanisms and dynamics of gene regulation.     

全光纤电流互感器的建模与仿真技术研究

在全光纤电流互感器物理模型的基础上,推导出了非线性动态模型,经过等效近似,建立了全光纤电流互感器的线性离散模型,并根据该模型对互感器的动态特性进行了仿真分析.同时,根据全光纤电流互感器的噪声特征建立了随机噪声模型,然后用不同的随机过程来模拟发生各种随机噪声.仿真结果表明：所建模型是合理的,模拟产生的随机噪声能够反映光纤电流互感器中噪声的统计特性.     

Zero-mode waveguides for single-molecule analysis at high concentrations

Optical approaches for observing the dynamics of single molecules have required pico- to nanomolar concentrations of fluorophore in order to isolate individual molecules. However, many biologically relevant processes occur at micromolar ligand concentrations, necessitating a reduction in the conventional observation volume by three orders of magnitude. We show that arrays of zero-mode waveguides consisting of subwavelength holes in a metal film provide a simple and highly parallel means for studying single-molecule dynamics at micromolar concentrations with microsecond temporal resolution. We present observations of DNA polymerase activity as an example of the effectiveness of zero-mode waveguides for performing single-molecule experiments at high concentrations.     

Genetic properties influencing the evolvability of gene expression

Identifying the properties of gene networks that influence their evolution is a fundamental research goal. However, modes of evolution cannot be inferred solely from the distribution of natural variation, because selection interacts with demography and mutation rates to shape polymorphism and divergence. We estimated the effects of naturally occurring mutations on gene expression while minimizing the effect of natural selection. We demonstrate that sensitivity of gene expression to mutations increases with both increasing trans-mutational target size and the presence of a TATA box. Genes with greater sensitivity to mutations are also more sensitive to systematic environmental perturbations and stochastic noise. These results provide a mechanistic basis for gene expression evolvability that can serve as a foundation for realistic models of regulatory evolution.     

A molecule carrier

We found that anthraquinone diffuses along a straight line across a flat, highly symmetric Cu111 surface. It can also reversibly attach one or two CO2 molecules as "cargo" and act as a "molecule carrier," thereby transforming the diffusive behavior of the CO2 molecules from isotropic to linear. Density functional theory calculations indicated a substrate-mediated attraction of approximately 0.12 electron volt (eV). Scanning tunneling microscopy revealed individual steps of the molecular complex on its diffusion pathway, with increases of approximately 0.03 and approximately 0.02 eV in the diffusion barrier upon attachment of the first and second CO2 molecule, respectively.     

Kinesin moves by an asymmetric hand-over-hand mechanism

Kinesin is a double-headed motor protein that moves along microtubules in 8-nanometer steps. Two broad classes of model have been invoked to explain kinesin movement: hand-over-hand and inchworm. In hand-over-hand models, the heads exchange leading and trailing roles with every step, whereas no such exchange is postulated for inchworm models, where one head always leads. By measuring the stepwise motion of individual enzymes, we find that some kinesin molecules exhibit a marked alternation in the dwell times between sequential steps, causing these motors to "limp" along the microtubule. Limping implies that kinesin molecules strictly alternate between two different conformations as they step, indicative of an asymmetric, hand-over-hand mechanism.     

Noisy clockwork: time series analysis of population fluctuations in animals

Both biotic interactions and abiotic random forcing are crucial influences on population dynamics. This frequently leads to roughly equal importance of deterministic and stochastic forces. The resulting tension between noise and determinism makes ecological dynamics unique, with conceptual and methodological challenges distinctive from those in other dynamical systems. The theory for stochastic, nonlinear ecological dynamics has been developed alongside methods to test models. A range of dynamical components has been considered-density dependence, environmental and demographic stochasticity, and climatic forcing-as well as their often complex interactions. We discuss recent advances in understanding ecological dynamics and testing theory using long-term data and review how dynamical forces interact to generate some central field and laboratory time series.     

Allelopathy and exotic plant invasion: from molecules and genes to species interactions

Here we present evidence that Centaurea maculosa (spotted knapweed), an invasive species in the western United States, displaces native plant species by exuding the phytotoxin (-)-catechin from its roots. Our results show inhibition of native species' growth and germination in field soils at natural concentrations of (-)-catechin. In susceptible species such as Arabidopsis thaliana, the allelochemical triggers a wave of reactive oxygen species (ROS) initiated at the root meristem, which leads to a Ca2+ signaling cascade triggering genome-wide changes in gene expression and, ultimately, death of the root system. Our results support a "novel weapons hypothesis" for invasive success.     

非自治随机 Sine-Gordon 方程组的拉回动力行为

主要研究了带加法扰动的非自治随机Sine-Gordon方程组的拉回动力行为,通过对解的一致估计证明了方程组产生的随机动力系统在空间(H_0~1(O)×L~2(O))~2上存在唯一的拉回吸引子.     

Extensive DNA inversions in the B. fragilis genome control variable gene expression

The obligately anaerobic bacterium Bacteroides fragilis, an opportunistic pathogen and inhabitant of the normal human colonic microbiota, exhibits considerable within-strain phase and antigenic variation of surface components. The complete genome sequence has revealed an unusual breadth (in number and in effect) of DNA inversion events that potentially control expression of many different components, including surface and secreted components, regulatory molecules, and restriction-modification proteins. Invertible promoters of two different types (12 group 1 and 11 group 2) were identified. One group has inversion crossover (fix) sites similar to the hix sites of Salmonella typhimurium. There are also four independent intergenic shufflons that potentially alter the expression and function of varied genes. The composition of the 10 different polysaccharide biosynthesis gene clusters identified (7 with associated invertible promoters) suggests a mechanism of synthesis similar to the O-antigen capsules of Escherichia coli.     

Microsatellite instability generates diversity in brain and sociobehavioral traits

Repetitive microsatellites mutate at relatively high rates and may contribute to the rapid evolution of species-typical traits. We show that individual alleles of a repetitive polymorphic microsatellite in the 5' region of the prairie vole vasopressin 1a receptor (avpr1a) gene modify gene expression in vitro. In vivo, we observe that this regulatory polymorphism predicts both individual differences in receptor distribution patterns and socio-behavioral traits. These data suggest that individual differences in gene expression patterns may be conferred via polymorphic microsatellites in the cis-regulatory regions of genes and may contribute to normal variation in behavioral traits.