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Trends Genet. 2011 Aug;27(8):323-31. doi: 10.1016/j.tig.2011.05.007. Epub 2011 Jun 22.

Molecular mechanisms of epistasis within and between genes.

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European Molecular Biology Laboratory-Centre for Genomic Regulation (EMBL-CRG) Systems Biology, the Catalan Institute of Research and Advanced Studies (ICREA), Centre for Genomic Regulation and the Pompeu Fabra University (UPF), c / Dr Aiguader 88, Barcelona 08003, Spain.


'Disease-causing' mutations do not cause disease in all individuals. One possible important reason for this is that the outcome of a mutation can depend upon other genetic variants in a genome. These epistatic interactions between mutations occur both within and between molecules, and studies in model organisms show that they are extremely prevalent. However, epistatic interactions are still poorly understood at the molecular level, and consequently difficult to predict de novo. Here I provide an overview of our current understanding of the molecular mechanisms that can cause epistasis, and areas where more research is needed. A more complete understanding of epistasis will be vital for making accurate predictions about the phenotypes of individuals.

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