Related papers: Epistasis not needed to explain low dN/dS

To determine the 3D conformation of proteins is a necessity to understand their functions or interactions with other molecules. It is commonly admitted that, when proteins fold from their primary linear structures to their final 3D…

The differing ability of polypeptide conformations to act as the native state of proteins has long been rationalized in terms of differing kinetic accessibility or thermodynamic stability. Building on the successful applications of physical…

Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to…

Quantitative understanding of the principles regulating nucleosome occupancy on a genome-wide level is a central issue in eukaryotic genomics. Here, we address this question using budding yeast, Saccharomyces cerevisiae, as a model…

We perform an exhaustive analysis of genome statistics for organisms, particularly extremophiles, growing in a wide range of physicochemical conditions. Specifically, we demonstrate how the correlation between the frequency of amino acids…

Intrinsically disordered proteins are fascinating the community of protein science since the last decade, at least. There is a well-established line of research that intends to reveal the crucial role played by intrinsically disordered…

Biases in molecular evolution can significantly influence evolutionary trajectories. They have been described in a variety of contexts such as development and mutation, but not for acquiring new functions (i.e. emergence). Here, we…

Enzymes are on the front lines of evolution. All living organisms rely on highly efficient, specific enzymes for growth, sustenance, and reproduction; and many diseases are a consequence of a mutation on an enzyme that affects its catalytic…

Proteins, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent to the indispensability of proteins for living cells is the fact that a given protein…

The percentage and sequence of AT and GC base pairs and charges on the DNA backbone contribute significantly to the stiffness of DNA. This elastic property of DNA also changes with small interacting ligands. The single-molecule force…

We consider a population evolving due to mutation, selection and recombination, where selection includes single-locus terms (additive fitness) and two-loci terms (pairwise epistatic fitness). We further consider the problem of inferring…

We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…

Epigenetic modifications of histones crucially affect the eukaryotic gene activity, while the epigenetic histone state is largely determined by the binding of specific factors such as the transcription factors (TFs) to DNA. Here, the way…

Fisher's geometric model was originally introduced to argue that complex adaptations must occur in small steps because of pleiotropic constraints. When supplemented with the assumption of additivity of mutational effects on phenotypic…

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…

We review and further develop an analytical model that describes how thermodynamic constraints on the stability of the native state influence protein evolution in a site-specific manner. To this end, we represent both protein sequences and…

The evolutionary fitness landscape of biological molecules is extremely sparse and heterogeneous, with functional sequences forming isolated dense ``islands'' within a vast combinatorial space of largely non-functional variants. Protein…

The relationship between the shape of a fitness landscape and the underlying gene interactions, or epistasis, has been extensively studied in the two-locus case. Gene interactions among multiple loci are usually reduced to two-way…

Native electrospray ionization/ion mobility-mass spectrometry (ESI/IM-MS) allows an accurate determination of low-resolution structural features of proteins. Yet, the presence of proton dynamics, observed already by us for DNA in the gas…

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.…