Epistasis

Epistasis is a phenomenon in genetics in which the effect of a mutation on a trait is dependent on the presence or absence of mutations at different loci (locations on the genome), that may be on the same gene (intragenic) or on different genes, called modifier genes. In evolutionary genetics, epistasis occurs when the combined effect of two mutations is different from what you would expect by simply adding their individual effects together. This definition can be expanded to more than two loci to study higher-order epistasis, which plays an important role in shaping evolutionary trajectories.

The term epistasis was introduced in 1907 to describe the discrepancy between the prediction of segregation ratios based on the action of individual genes and the actual outcome of a dihybrid cross, and is now widely used in biochemistry, computational biology and evolutionary biology. While the nuanced meaning of the term now differs between researchers studying genetics at a functional, compositional, or at a statistical level, it still describes gene interactions at various levels.

History

Understanding of epistasis has changed considerably through the history of genetics and so too has the use of the term. The term was first used in 1907 by William Bateson and his collaborators Florence Durham and Muriel Wheldale Onslow. In early models of natural selection devised in the early 20th century, each gene was considered to make its own characteristic contribution to fitness, against an average background of other genes. Some introductory courses still teach population genetics this way. Because of the way that the science of population genetics was developed, evolutionary geneticists have tended to think of epistasis as the exception.