Related papers: Dynamics of transcription factor binding site evol…
Protein evolution involves mutations occurring across a wide range of time scales. In analogy with disordered systems in statistical physics, this dynamical heterogeneity suggests strong correlations between mutations happening at distinct…
We study a simple model of DNA evolution in a growing population of cells. Each cell contains a nucleotide sequence which randomly mutates at cell division. Cells divide according to a branching process. Following typical parameter values…
Genetic oscillators, such as circadian clocks, are constantly perturbed by molecular noise arising from the small number of molecules involved in gene regulation. One of the strongest sources of stochasticity is the binary noise that arises…
Transcription factor (TF) molecules translocate by facilitated diffusion (a combination of 3D diffusion around and 1D random walk on the DNA). Despite the attention this mechanism received in the last 40 years, only a few studies…
It is well known that, under suitable conditions, microRNAs are able to fine tune the relative concentration of their targets to any desired value. We show that this function is particularly effective when one of the targets is a…
Gene expression is controlled primarily by interactions between transcription factor proteins (TFs) and the regulatory DNA sequence, a process that can be captured well by thermodynamic models of regulation. These models, however, neglect…
Differences in transcriptional regulatory networks underlie much of the phenotypic variation observed across organisms. Changes to cis-regulatory elements are widely believed to be the predominant means by which regulatory networks evolve,…
Transcription Factors (TFs) are proteins that regulate gene expression. The regulation mechanism is via the binding of a TF to a specific part of the gene associated with it, the TF's target. The target of a specific TF corresponds to a…
We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses…
The activation/repression of a given gene is typically regulated by multiple transcription factors (TFs) that bind at the gene regulatory region and recruit RNA polymerase (RNAP). The interactions between the promoter region and TFs and…
We present ensemble methods in a machine learning (ML) framework combining predictions from five known motif/binding site exploration algorithms. For a given TF the ensemble starts with position weight matrices (PWM's) for the motif,…
This paper focuses on the maximum speed at which biological evolution can occur. I derive inequalities that limit the rate of evolutionary processes driven by natural selection, mutations, or genetic drift. These \emph{rate limits} link the…
We present a detailed analysis, based on the Forward Flux Sampling (FFS) simulation method, of the switching dynamics and stability of two models of genetic toggle switches, consisting of two mutually-repressing genes encoding transcription…
In the simplest view of transcriptional regulation, the expression of a gene is turned on or off by changes in the concentration of a transcription factor (TF). We use recent data on noise levels in gene expression to show that it should be…
DNA shape readout is an important mechanism of target site recognition by transcription factors, in addition to the sequence readout. Several models of transcription factor-DNA binding which consider DNA shape have been developed in recent…
The site frequency spectrum (SFS) is a popular summary statistic of genomic data. While the SFS of a constant-sized population undergoing neutral mutations has been extensively studied in population genetics, the rapidly growing amount of…
The binding of transcription factors (TFs) is essential for gene expression. One important characteristic is the actual occupancy of a putative binding site in the genome. In this study, we propose an analytical model to predict genomic…
Transcription is a fundamental cellular process, and the first step of gene expression. In human cells, it depends on the binding to chromatin of various proteins, including RNA polymerases and numerous transcription factors (TFs).…
Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons which have remained unexplained. Here, we…
Protein synthesis rates are determined, at the translational level, by properties of the transcript's sequence. The efficiency of an mRNA can be tuned by varying the ribosome binding sites controlling the recruitment of the ribosomes, or…