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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…

Molecular Networks · Quantitative Biology 2015-02-11 Brandon Barker , Lin Xu , Zhenglong Gu

Biochemical and regulatory interactions central to biological networks are expected to cause extensive genetic interactions or epistasis affecting the heritability of complex traits and the distribution of genotypes in populations. However,…

Populations and Evolution · Quantitative Biology 2009-12-15 Richard A. Neher , Boris I. Shraiman

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…

Populations and Evolution · Quantitative Biology 2014-11-14 Benjamin H. Good , Michael M. Desai

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 -…

Populations and Evolution · Quantitative Biology 2015-03-19 Steffen Schaper , Iain G. Johnston , Ard A. Louis

The contribution to an organism's phenotype from one genetic locus may depend upon the status of other loci. Such epistatic interactions among loci are now recognized as fundamental to shaping the process of adaptation in evolving…

Populations and Evolution · Quantitative Biology 2012-12-18 Jeremy A. Draghi , Joshua B. Plotkin

We investigate the relationship between the average fitness decay due to single mutations and the strength of epistatic interactions in genetic sequences. We observe that epistatic interactions between mutations are correlated to the…

Biological Physics · Physics 2007-05-23 Claus O. Wilke , Christoph Adami

The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the…

Populations and Evolution · Quantitative Biology 2015-06-11 Premal Shah , David M. McCandlish , Joshua B. Plotkin

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…

Populations and Evolution · Quantitative Biology 2022-06-13 Claudia Bank

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…

Populations and Evolution · Quantitative Biology 2019-10-22 Kabir Husain , Arvind Murugan

Every now and then the cultural paradigm of a society changes. Human history can be regarded as a sequence of long periods of cultural stasis punctuated by paradigm shifts that transform culture upside-down over the turn of a few…

Physics and Society · Physics 2020-06-04 Ignacio Pascual , Jacobo Aguirre , Susanna Manrubia , José A. Cuesta

Epistasis (gene-gene interaction) is crucial to predicting genetic disease. Our work tackles the computational challenges faced by previous works in epistasis detection by modeling it as a one-step Markov Decision Process where the state is…

Machine Learning · Computer Science 2018-09-26 Kexin Huang , Rodrigo Nogueira

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…

Populations and Evolution · Quantitative Biology 2022-10-10 Juan Diaz-Colunga , Abigail Skwara , Karna Gowda , Ramon Diaz-Uriarte , Mikhail Tikhonov , Djordje Bajic , Alvaro Sanchez

The mutation rate of a well adapted population is prone to reduction so as to have a lower mutational load. We aim to understand the role of epistatic interactions between the fitness affecting mutations in this process. Using a multitype…

Populations and Evolution · Quantitative Biology 2016-09-20 Ananthu James

Genetic interactions pervade every aspect of biology, from evolutionary theory where they determine the accessibility of evolutionary paths, to medicine where they contribute to complex genetic diseases. Until very recently, studies on…

Genomics · Quantitative Biology 2014-01-20 Andrea Velenich , Jeff Gore

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…

An important question in molecular evolution is whether an amino acid that occurs at a given position makes an independent contribution to fitness, or whether its effect depends on the state of other loci in the organism's genome, a…

Populations and Evolution · Quantitative Biology 2013-09-05 David M. McCandlish , Etienne Rajon , Premal Shah , Yang Ding , Joshua B. Plotkin

The interconnected processes of protein folding, mutations, epistasis, and evolution have all been the subject of extensive analysis throughout the years due to their significance for structural and evolutionary biology. The origin…

Populations and Evolution · Quantitative Biology 2024-04-08 Jorge A. Vila

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…

Populations and Evolution · Quantitative Biology 2023-12-05 Juan Li , Claudia Bank

We introduce a data-driven epistatic model of protein evolution, capable of generating evolutionary trajectories spanning very different time scales reaching from individual mutations to diverged homologs. Our in silico evolution…

Biomolecules · Quantitative Biology 2024-09-30 Leonardo Di Bari , Matteo Bisardi , Sabrina Cotogno , Martin Weigt , Francesco Zamponi

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…

Genomics · Quantitative Biology 2014-06-04 Chris H. Chandler , Sudarshan Chari , Ian Dworkin
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