1160 PERSPECTIVES P ropagating bacteria in a lab for thousands of generations may seem tedious, or even irrelevant, to most evolutionary biologists. Nonetheless, such experiments provide an opportunity to deduce quantitative principles of evolution and directly test them in controlled environments. Combined with modern sequencing technologies , as well as theory, recent microbial experiments ha...

Mice lacking the gene for the IL-1R antagonist (IL-1ra) show abnormal development and homeostasis as well as altered responses to infectious and inflammatory stimuli. A reduction in the level of IL-1 signaling, either by deletion of the receptor or increased expression of IL-1ra, does not affect development or homeostasis, but does alter immune responses. In this study we use genetic epistasis ...

Epistasis arising from physiological interactions between gene products often contributes to species differences, particularly those involved in reproductive isolation. In social organisms, phenotypes are influenced by the genotypes of multiple interacting individuals. In theory, social interactions can give rise to an additional type of epistasis between the genomes of social partners that can...

The missing heritability exhibited by late-onset Alzheimer's disease is unexplained and has been partly attributed to epistatic interaction. Methods available to explore this are often based on logistic regression and allow for determination of deviation from an expected outcome as a result of statistical epistasis. Three such methodologies including Synergy Factor and the PLINK modules, -epist...

Genetic epidemiologists strive to determine the genetic profile of diseases. Epistasis is the interaction between two or more genes to affect phenotype. Due to the often non-linearity of the interaction, it is difficult to detect statistical patterns of epistasis. Combinatorial methods for detecting epistasis investigate a subset of combinations of genes without employing a search strategy. The...

Identification of genetic loci in complex traits has focused largely on one-dimensional genome scans to search for associations between single markers and the phenotype. There is mounting evidence that locus interactions, or epistasis, are a crucial component of the genetic architecture of biologically relevant traits. While discussion about the best way to identify models for complex traits is...

Linkage disequilibrium (LD) plays a central role in current and proposed methods for mapping complex disease genes. LD-based methods work best when there is a single susceptibility allele at any given disease locus, and generally perform very poorly if there is substantial allelic heterogeneity. The extent of allelic heterogeneity at typical complex disease loci is not yet known, but prediction...

Epistasis, the interaction among genes, is ubiquitous among common, complex, and multifactorial diseases. Therefore it has become necessary to develop methods to detect epistasis, the motivation for one such method, multifactor dimensionality reduction (MDR). We introduce the algorithm of MDR, its strengths and weaknesses, and finally illustrate the results of applying MDR to alcoholism. We com...

Epistatic interactions, manifested in the effects of mutations on the phenotypes caused by other mutations, may help uncover the functional organization of complex biological networks1–3. Here, we studied system-level epistatic interactions by computing growth phenotypes of all single and double knockouts of 890 metabolic genes in Saccharomyces cerevisiae, using the framework of flux balance an...

Epistasis has substantial impacts on evolution, in particular, the rate of adaptation. We generated combinations of beneficial mutations that arose in a lineage during rapid adaptation of a bacterium whose growth depended on a newly introduced metabolic pathway. The proportional selective benefit for three of the four loci consistently decreased when they were introduced onto more fit backgroun...