Related papers: Neutral genetic drift can aid functional protein e…

Protein binding and function often involves conformational changes. Advanced NMR experiments indicate that these conformational changes can occur in the absence of ligand molecules (or with bound ligands), and that the ligands may 'select'…

Gene expression is a biochemical process, where stochastic binding and un-binding events naturally generate fluctuations and cell-to-cell variability in gene dynamics. These fluctuations typically have destructive consequences for proper…

Directed evolution plays an indispensable role in protein engineering that revises existing protein sequences to attain new or enhanced functions. Accurately predicting the effects of protein variants necessitates an in-depth understanding…

Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

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.…

Evolving genomes increase a number of their genes by gene duplications. To escape degradation in a functionless pseudogene, any gene duplicate needs to be guarded by negative (purifying) selection from otherwise inevitable fixation of…

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…

Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…

A gene's rate of sequence evolution is among the most fundamental evolutionary quantities in common use, but what determines evolutionary rates has remained unclear. Here, we show that the two most commonly used methods to disentangle the…

The premise of genetic analysis is that a causal link exists between phenotypic and allelic variation. Yet it has long been documented that mutant phenotypes are not a simple result of a single DNA lesion, but rather are due to interactions…

A central goal of evolutionary biology is to explain the origins and distribution of diversity across life. Beyond species or genetic diversity, we also observe diversity in the circuits (genetic or otherwise) underlying complex functional…

An elastic spring network is an example of evolvable matter. It can be pruned to couple separated pairs of nodes so that when a strain is applied to one of them, the other responds either in-phase or out-of-phase. This produces two pruned…

The ability to absorb mutations while retaining structure and function, or mutational robustness, is a remarkable property of natural proteins. In this Letter, we use a computational model of organismic evolution [Zeldovich et al, PLOS Comp…

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…

Most of the DNA that composes a complex organism is non-coding and defined as junk. Even the coding part is composed of genes that affect the phenotype differently. Therefore, a random mutation has an effect on the specimen fitness that…

Gene expression is significantly stochastic making modeling of genetic networks challenging. We present an approximation that allows the calculation of not only the mean and variance but also the distribution of protein numbers. We assume…

Epistasis refers to the phenomenon in which phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is critical for understanding many genetic and evolutionary processes, including…

In classical evolutionary theory, genetic variation provides the source of heritable phenotypic variation on which natural selection acts. Against this classical view, several theories have emphasized that developmental variability and…

Non-genetic perturbations, such as environmental change or developmental noise, can induce novel phenotypes. If an induced phenotype confers a fitness advantage, selection may promote its genetic stabilization. Non-genetic perturbations can…