Related papers: Strong Selection Significantly Increases Epistatic…
Human immunodeficiency virus (HIV) evolves with extraordinary rapidity. However, its evolution is constrained by interactions between mutations in its fitness landscape. Here we show that an Ising model describing these interactions,…
We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of quasispecies type equipped with a mesa shaped fitness landscape. We obtain…
Drug resistance to HIV-1 Protease involves accumulation of multiple mutations in the protein. Here we investigate the role of these mutations by using molecular dynamics simulations which exploit the influence of the native-state topology…
As pathogens spread in a population of hosts, immunity is built up and the pool of susceptible individuals is depleted. This generates selective pressure, to which many human RNA viruses, such as influenza virus or SARS-CoV-2, respond with…
Emergence of new protein structures has proved difficult to trace in nature and engineer in the laboratory. However, one aspect of structure evolution has proved immensely helpful for determining the three-dimensional structure of proteins…
Darwinian evolution is driven by random mutations, genetic recombination (gene shuffling) and selection that favors genotypes with high fitness. For systems where each genotype can be represented as a bitstring of length $L$, an overview of…
Two processes can influence the evolution of protein interaction networks: addition and elimination of interactions between proteins, and gene duplications increasing the number of proteins and interactions. The rates of these processes can…
Evolving systems, be it an antibody repertoire in the face of mutating pathogens or a microbial population exposed to varied antibiotics, constantly search for adaptive solutions in time-varying fitness landscapes. Generalists correspond to…
The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an…
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…
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…
In this work, we integrate theoretical modeling, molecular simulation, and empirical analysis to identify and characterize evolutionary hysteresis. We first show how epistatic interactions create bistable fitness landscapes and structural…
Major advances in large-scale yeast two hybrid (Y2H) screening have provided a global view of binary protein-protein interactions across species as dissimilar as human, yeast, and bacteria. Remarkably, these analyses have revealed that all…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
How typical elements that shape organisms, such as protein secondary structures, have evolved, or how evolutionarily susceptible/resistant they are to environmental changes, are significant issues in evolutionary biology, structural…
Biological evolution of a population is governed by the fitness landscape, which is a map from genotype to fitness. However, a fitness landscape depends on the organisms environment, and evolution in changing environments is still poorly…
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…
Dominance is usually considered a constant value that describes the relative difference in fitness or phenotype between heterozygotes and the average of homozygotes at a focal polymorphic locus. However, the observed dominance can vary with…
The tendency of repeating past choices more often than expected from the history of outcomes has been repeatedly empirically observed in reinforcement learning experiments. It can be explained by at least two computational processes:…
Approaches to gene interactions based on sign epistasis have been highly influential in recent time. Sign epistasis is useful for relating local and global properties of fitness landscapes, as well as for analyzing evolutionary trajectories…