Epistasis

![Quantitative trait values after two mutations either alone (Ab and aB) or in combination (AB). Bars contained in the grey box indicate the combined trait value under different circumstances of epistasis. Upper panel indicates epistasis between beneficial mutations (blue).[5][6] Lower panel indicates epistasis between deleterious mutations (red).[7][8]](/uploads/202501/11/Epistasis_bars4136.png)
![Since, on average, mutations are deleterious, random mutations to an organism cause a decline in fitness. If all mutations are additive, fitness will fall proportionally to mutation number (black line). When deleterious mutations display negative (synergistic) epistasis, they are more deleterious in combination than individually and so fitness falls with the number of mutations at an increasing rate (upper, red line). When mutations display positive (antagonistic) epistasis, effects of mutations are less severe in combination than individually and so fitness falls at a decreasing rate (lower, blue line).[7][8][9][10]](/uploads/202501/11/Synergistic_versus_antagonistic_epistasis.svg4136.png)

Epistasis is the phenomenon of the effect of one gene being dependent on the presence of one or more 'modifier genes', the genetic background. Thus, epistatic mutations have different effects in combination than individually. It was originally a concept from genetics but is now used in biochemistry, computational biology and evolutionary biology. It arises due to interactions, either between genes, or within them, leading to non-additive effects. Epistasis has a large influence on the shape of evolutionary landscapes, which leads to profound consequences for evolution and evolvability of phenotype traits.