Related papers: Mutation Rate Variation Across Genomic Regions in …
Epigenetics plays a key role in cellular differentiation and maintaining cell identity, enabling cells to regulate their genetic activity without altering the DNA sequence. Epigenetic regulation occurs within the context of hierarchically…
A central problem when studying adaptation to a new environment is the interplay between genetic variation and phenotypic plasticity. Arabidopsis thaliana has colonized a wide range of habitats across the world and it is therefore an…
Chromatin is repeatedly deformed in vivo during transcription, nuclear remodeling, and confined migration - yet how mechanical response varies from locus to locus, and how it relates to epigenetic state, remains unclear. We develop a theory…
A problem of substantial interest is to systematically map variation in chromatin structure to gene expression regulation across conditions, environments, or differentiated cell types. We developed and applied a quantitative framework for…
This study presents the first global, 1 Mbp level analysis of patterns of nucleotide substitutions along the human lineage. The study is based on the analysis of a large amount of repetitive elements deposited into the human genome since…
Histone modification is a vital epigenetic mechanism for transcriptional control in eukaryotes. High-throughput techniques have enabled whole-genome analysis of histone modifications in recent years. However, most studies assume one…
A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (1982) that overcome the weak selection constraints needed for tractability in prior studies of…
Gene expression levels exhibit stochastic variations among genetically identical organisms under the same environmental conditions (called gene expression "noise" or phenotype "fluctuation"). In yeast and Escherichia coli, positive…
We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher…
In the human genomes, recombination frequency between homologous chromosomes during meiosis is highly correlated with their physical length while it differs significantly when their coding density is considered. Furthermore, it has been…
Phylogenetics uses alignments of molecular sequence data to learn about evolutionary trees relating species. Along branches, sequence evolution is modelled using a continuous-time Markov process characterised by an instantaneous rate…
Chromatin is a highly compact and dynamic nuclear structure that consists of DNA and associated proteins. The main organizational unit is the nucleosome, which consists of a histone octamer with DNA wrapped around it. Histone proteins are…
It has been recently claimed that it is possible to predict the rate of de novo mutation of each site in the human genome with almost perfect accuracy (Michaelson et al. (2012) Cell, 151, 1431-1442). We show that this claim is unwarranted.…
Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…
Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code,…
We propose and analyze a stochastic model to investigate epigenetic mutations, i.e., modifications of the genetic information that control gene expression patterns in a cell but do not alter the DNA sequence. Epigenetic mutations are…
Essential life processes take place across multiple space and time scales in living organisms but understanding their mechanistic interactions remains an ongoing challenge. Advanced multiscale modeling techniques are providing new…
Epigenetic modifications to histones may promote either activation or repression of the transcription of nearby genes. Recent experimental studies show that the promoters of many lineage-control genes in stem cells have "bivalent domains"…
Post-genomic research deals with challenging problems in screening genomes of organisms for particular functions or potential for being the targets of genetic engineering for desirable biological features. 'Phenotyping' of wild type and…
When mutation rates are low, natural selection remains effective, and increasing the mutation rate can give rise to an increase in adaptation rate. When mutation rates are high to begin with, however, increasing the mutation rate may have a…