A common high school science experiment involves anchoring one end of a rubber band to a desk and then attaching a small weight to the other end. The weight stretches the rubber band, and adding another weight causes the rubber band to dangle even lower. More weights can be added, and each one pulls the rubber band a little further towards the floor. Now, instead imagine attaching the weights t...

Evolutionary biologists have identified several factors that could explain the widespread phenomena of sex and recombination. One hypothesis is that host-parasite interactions favor sex and recombination because they favor the production of rare genotypes. A problem with many of the early models of this so-called Red Queen hypothesis is that several factors are acting together: directional sele...

Background Epistatic interactions among genomic loci are expected to explain a large fraction of the heritability of complex diseases and phenotypic traits of living organisms. Although epistasis detection methods are continually being developed, the current state of the art is exhaustive search methods, which become infeasible when the number of analyzed loci is large. Results We develop a nov...

We use the ancestral influence graph (AIG) for a two-locus, two-allele selection model in the limit of a large population size to obtain an analytic approximation for the probability of ultimate fixation of a single mutant allele A. We assume that this new mutant is introduced at a given locus into a finite population in which a previous mutant allele B is already segregating with a wild type a...

7 8 The nature of epistasis has important consequences for the evolutionary significance of sex and recombination. Recent efforts to find negative epistasis as source of negative linkage disequilibrium and associated long-term sex advantage have yielded little support. Sign epistasis, where the sign of the fitness effects of alleles varies across genetic backgrounds, is responsible for ruggedne...

There has been growing evidence that cooperative interactions and configurational rearrangements underpin protein functions. But in spite of vast genetic and structural data, the information-dense, heterogeneous nature of protein has held back the progress in understanding the underlying principles. Here we outline a general theory of protein that quantitatively links sequence, dynamics and fun...

The line value of a genotype is defined as the expected value of all lines that can be derived from this genotype. Specific genetic effects are defined for this value: only additive and additive by additive epistatic effects are necessary. There is no dominance effect for such a value. A general expression for the covariances between related lines is given. From a design with several lines per ...

The relative contributions of additive versus non-additive interactions in the regulation of complex traits remains controversial. This may be in part because large-scale epistasis has traditionally been difficult to detect in complex, multi-cellular organisms. We hypothesized that it would be easier to detect interactions using mouse chromosome substitution strains that simultaneously incorpor...

The fitness effects of a mutation can depend, sometimes dramatically, on genetic background; this phenomenon is often referred to as "epistasis." Epistasis can have important practical consequences in the context of antimicrobial resistance (AMR). For example, genetic background plays an important role in determining the costs of resistance, and hence in whether resistance will persist in the a...

Many bacterial lineages lack seemingly essential metabolic genes. Previous work suggested selective benefits could drive the loss of biosynthetic functions from bacterial genomes when the corresponding metabolites are sufficiently available in the environment. However, the factors that govern this "genome streamlining" remain poorly understood. Here we determine the effect of plasticity and epi...