Related papers: Lethal Mutagenesis in Viruses and Bacteria
The stability of model proteins with designed sequences is assessed in terms of the number of sequences (obtained from the designed sequence through mutations), which fold into 5the ``native'' conformation. By a complete enumeration of the…
In this work we propose a physical model of organismal evolution, where phenotype, organism life expectancy, is directly related to genotype i.e. the stability of its proteins which can be determined exactly in the model. Simulating the…
The emergence of a predominant phenotype within a cell population is often triggered by a rare accumulation of DNA mutations in a single cell. For example, tumors may be initiated by a single cell in which multiple mutations cooperate to…
The observation that phenotypic variability is ubiquitous in isogenic populations has led to a multitude of experimental and theoretical studies seeking to probe the causes and consequences of this variability. Whether it be in the context…
Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…
Most human tumors result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Mutations that confer a fitness advantage to the cell are known as driver mutations and are causally related to tumorigenesis.…
Evolution occurs in populations of reproducing individuals. It is well known that population structure can affect evolutionary dynamics. Traditionally, natural selection is studied between mutants that differ in reproductive rate, but are…
We consider a stochastic model for an evolving population. We show that in the presence of genotype extinctions the population dies out for a low mutation probability but may survive for a high mutation probability. This turns upside down…
The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous…
Evolution on neutral networks of genotypes has been found in models to concentrate on genotypes with high mutational robustness, to a degree determined by the topology of the network. Here analysis is generalized beyond neutral networks to…
We investigate the process of fixation of advantageous mutations in an asexual population. We assume that the effect of each beneficial mutation is exponentially distributed with mean value $\omega_{med}=1/\beta$. The model also considers…
One of the most challenging problems in microbiology is to understand how a small fraction of microbes that resists killing by antibiotics can emerge in a population of genetically identical cells, the phenomenon known as persistence or…
Stochastic phenotype switching has been suggested to play a beneficial role in microbial populations by leading to the division of labour among cells, or ensuring that at least some of the population survives an unexpected change in…
Because mutations are mostly deleterious, mutation rates should be reduced by natural selection. However, mutations also provide the raw material for adaptation. Therefore, evolutionary theory suggests that the mutation rate must balance…
Antigenic variation is the main immune escape mechanism for RNA viruses like influenza or SARS-CoV-2. While high mutation rates promote antigenic escape, they also induce large mutational loads and reduced fitness. It remains unclear how…
Antibodies, an essential part of our immune system, develop through an intricate process to bind a wide array of pathogens. This process involves randomly mutating DNA sequences encoding these antibodies to find variants with improved…
Evolutionary analyses of large populations commonly incorporate stochasticity through temporal variation in selection while treating genetic transmission as fixed. Much less attention has been given to stochasticity in transmission itself.…
We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state, thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We…
When polygenic traits are under stabilizing selection, many different combinations of alleles allow close adaptation to the optimum. If alleles have equal effects, all combinations that result in the same deviation from the optimum are…
A mutation in a protein-coding gene in DNA can alter the protein structure coded by the same gene. Structurally altered proteins usually lose their functions and sometimes gain an undesirable function instead. These types of mutations and…