Related papers: Adaptive evolution of transcription factor binding…
Cells integrate signals and make decisions about their future state in short amounts of time. A lot of theoretical effort has gone into asking how to best design gene regulatory circuits that fulfill a given function, yet little is known…
While coding regions in the genome have a direct interpretation in terms of protein products, significant fractions are non-coding and yet control essential biological functions. Unlike the genetic code, there is no "lookup table" that…
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…
Mutation rate is a key determinant of the pace as well as outcome of evolution, and variability in this rate has been shown in different scenarios to play a key role in evolutionary adaptation and resistance evolution under stress caused by…
The day we understand the time evolution of subcellular elements at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our…
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,…
Understanding the differentiation, a biological process from a multipotent stem or progenitor state to a mature cell is critically important. We develop a theoretical framework to quantify the underlying potential landscape and biological…
Phenotypic evolution implies sequential fixations of new genomic sequences. The speed at which these mutations fixate depends, in part, on the relative fitness (selection coefficient) of the mutant vs. the ancestor. Using a simple…
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…
The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci and the genome-wide patterns of polymorphism show signatures consistent with…
Residue-residue interactions that fold a protein into a unique three-dimensional structure and make it play a specific function impose structural and functional constraints on each residue site. Selective constraints on residue sites are…
In eukaryotic genomes, nucleosomes function to compact DNA and to regulate access to it both by simple physical occlusion and by providing the substrate for numerous covalent epigenetic tags. While nucleosome positions in vitro are…
Current models for the folding of the human genome see a hierarchy stretching down from chromosome territories, through A/B compartments and TADs (topologically-associating domains), to contact domains stabilized by cohesin and CTCF.…
Which factors govern the evolution of mutation rates and emergence of species? Here, we address this question using a first principles model of life where population dynamics of asexual organisms is coupled to molecular properties and…
The Hill coefficient is often used as a direct measure of the cooperativity of binding processes. It is an essential tool for probing properties of reactions in many biochemical systems. Here we analyze existing experimental data and…
It has been reported that the number of transcription factors encoded in prokaryotic genomes scales approximately quadratically with their total number of genes. We propose a conceptual explanation of this finding and illustrate it using a…
In evolutionary dynamics, a key measure of a mutant trait's success is the probability that it takes over the population given some initial mutant-appearance distribution. This "fixation probability" is difficult to compute in general, as…
One of the outstanding challenges in comparative genomics is to interpret the evolutionary importance of regulatory variation between species. Rigorous molecular evolution-based methods to infer evidence for natural selection from…
How adaptive evolution to one environmental stress improves or suppresses adaptation to another is an important problem in evolutionary biology. For instance, in microbiology, the evolution of bacteria to be resistant to different…
Search for possible relationships between phylogeny and ontogeny is one of the most important issues in the field of evolutionary developmental biology. By representing developmental dynamics of spatially located cells with gene expression…