Related papers: Functional bottlenecks can emerge from non-epistat…
Epistatic interactions between mutations add substantial complexity to adaptive landscapes, and are often thought of as detrimental to our ability to predict evolution. Yet, patterns of global epistasis, in which the fitness effect of a…
Epistasis occurs when the effect of a mutation depends on its carrier's genetic background. Despite increasing evidence that epistasis for fitness is common, its role during evolution is contentious. Fitness landscapes, mappings of genotype…
Genotypic fitness landscapes are constructed by assessing the fitness of all possible combinations of a given number of mutations. In the last years, several experimental fitness landscapes have been completely resolved. As fitness…
In epistatic fitness landscapes, the fitness effect of a mutation depends on the genetic background and may even switch between deleterious and beneficial depending on the presence of another mutation. Epistatic interactions may cause both…
The class of epistatic fitness landscapes is much more diverse than the class of non-epistatic landscapes, and so it stands to reason that there exist dynamical phenomena that can only be realized in the presence of epistasis. Here, we…
The genotype-fitness map plays a fundamental role in shaping the dynamics of evolution. However, it is difficult to directly measure a fitness landscape in practice, because the number of possible genotypes is astronomical. One approach is…
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…
The factors that influence genetic architecture shape the structure of the fitness landscape, and therefore play a large role in the evolutionary dynamics. Here the NK model is used to investigate how epistasis and pleiotropy -- key…
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…
Living systems evolve one mutation at a time, but a single mutation can alter the effect of subsequent mutations. The underlying mechanistic determinants of such epistasis are unclear. Here, we demonstrate that the physical dynamics of a…
Darwinian evolution can be illustrated as an uphill walk in a landscape, where the surface consists of genotypes, the height coordinates represent fitness, and each step corresponds to a point mutation. Epistasis, roughly defined as the…
Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…
The fitness landscape defines the relationship between genotypes and fitness in a given environment, and underlies fundamental quantities such as the distribution of selection coefficient, or the magnitude and type of epistasis. A better…
The concept of a fitness landscape is a powerful metaphor that offers insight into various aspects of evolutionary processes and guidance for the study of evolution. Until recently, empirical evidence on the ruggedness of these landscapes…
Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness…
Fitness functions map large combinatorial spaces of biological sequences to properties of interest. Inferring these multimodal functions from experimental data is a central task in modern protein engineering. Global epistasis models are an…
Fitness landscapes provide a quantitative framework for understanding how natural selection shapes evolutionary trajectories. A central feature of these landscapes is their number of local optima, which determines whether fitness-increasing…
Epistasis describes the phenomenon that mutations at different loci do not have independent effects with regard to certain phenotypes. Understanding the global epistatic landscape is vital for many genetic and evolutionary theories. Current…
Genetic interactions can strongly influence the fitness effects of individual mutations, yet the impact of these epistatic interactions on evolutionary dynamics remains poorly understood. Here we investigate the evolutionary role of…
In evolution, the effects of a single deleterious mutation can sometimes be compensated for by a second mutation which recovers the original phenotype. Such epistatic interactions have implications for the structure of genome space -…