相关论文: Evolutionary dynamics determines adaptation to ina…
Protein function often involves changes between different conformations. Central questions are how these conformational changes are coupled to the binding or catalytic processes during which they occur, and how they affect the catalytic…
The relationship between sequence variation and phenotype is poorly understood. Here we use metabolomic analysis to elucidate the molecular mechanism underlying the filamentous phenotype of E. coli strains that carry destabilizing mutations…
Mutations create the genetic diversity on which selective pressures can act, yet also create structural instability in proteins. How, then, is it possible for organisms to ameliorate mutation-induced perturbations of protein stability while…
The importance of mutator clones in the adaptive evolution of asexual populations is not fully understood. Here we address this problem by using an ab initio microscopic model of living cells, whose fitness is derived directly from their…
Even closely related prokaryotes show an astounding diversity in their ability to grow in different nutritional environments. Mechanistically, this diversity arises predominantly through horizontal gene transfer, the exchange of DNA between…
Gene expression levels are important molecular quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies in recent years have revealed substantial adaptive evolution at the genomic…
Antibiotic resistance is a worldwide challenge. A potential approach to block resistance is to simultaneously inhibit WT and known escape variants of the target bacterial protein. Here we applied an integrated computational and experimental…
Despite recent advances in our ability to detect adaptive evolution involving the cis-regulation of gene expression, our knowledge of the molecular mechanisms underlying these adaptations has lagged far behind. Across all model organisms…
Elucidating the architecture and dynamics of large scale genetic regulatory networks of cells is an important goal in systems biology. We study the system level dynamical properties of the genetic network of Escherichia coli that regulates…
Genes are connected in complex networks of interactions where often the product of one gene is a transcription factor that alters the expression of another. Many of these networks are based on a few fundamental motifs leading to switches…
Fitness effects of mutations fall on a continuum ranging from lethal to deleterious to beneficial. The distribution of fitness effects (DFE) among random mutations is an essential component of every evolutionary model and a mathematical…
Understanding the organization of reaction fluxes in cellular metabolism from the stoichiometry and the topology of the underlying biochemical network is a central issue in systems biology. In this task, it is important to devise reasonable…
Antagonistic interactions in biological systems, which occur when one perturbation blunts the effect of another, are typically interpreted as evidence that the two perturbations impact the same cellular pathway or function. Yet, this…
Regulatory networks have evolved to allow gene expression to rapidly track changes in the environment as well as to buffer perturbations and maintain cellular homeostasis in the absence of change. Theoretical work and empirical…
Recent studies have consistently inferred high rates of adaptive molecular evolution between Drosophila species. At the same time, the Drosophila genome evolves under different rates of recombination, which results in partial genetic…
Regulatory networks consist of interacting molecules with a high degree of mutual chemical specificity. How can these molecules evolve when their function depends on maintenance of interactions with cognate partners and simultaneous…
Biological evolution of a population is governed by the fitness landscape, which is a map from genotype to fitness. However, a fitness landscape depends on the organisms environment, and evolution in changing environments is still poorly…
A fundamental question for evolutionary biology is why rates of evolution vary dramatically between proteins. Perhaps surprisingly, it is controversial how much a protein's functional importance affects its rate of evolution. In most…
Eukaryotic cells are often exposed to fluctuations in growth conditions as well as endogenous and exogenous stress-related agents. In addition, during development global patterns of gene transcription change dramatically, and these changes…
The phage $\lambda$ infection of an \textit{E. coli} cell has become a paradigm for understanding the molecular processes involved in gene expression and cell signaling. This system provides an example of a genetic switch, as cells with…