Quote: Fisher defining epistasis

People often complain that R. A. Fisher wrote in a hard-to-read style; unnecessarily verbose and indirect. Either I don’t tend to mind, or I find that the style makes me read with greater care. In either case, there are select passages from his writings that stand out as very clear to me. His description of epistasis and dominance as deviations from additivity, in his famous 1918 paper (p. 404), is one of them:

The steps from recessive to heterozygote and from heterozygote to dominant are genetically identical, and may change from one to the other in passing from father to son. Somatically the steps are of different importance, and the soma to some extent disguises the true genetic nature. There is in dominance a certain latency. We may say that the somatic effects of identical genetic changes are not additive, and for this reason the genetic similarity of relations is partly obscured in the statistical aggregate. A similar deviation from the addition of superimposed effects may occur between different Mendelian factors. We may use the term Epistacy to describe such deviation, which although potentially more complicated, has similar statistical effects to dominance. If the two sexes are considered as Mendelian alternatives, the fact that other Mendelian factors affect them to different extents may be regarded as an example of epistacy.

The terms we use today are familiar by use. A biologist doesn’t necessary consider how idiosyncratic is the genetic use of term “additive”. When I read a passage like this, it brings to mind a long-ago time when the select group of people using a term all had read the same papers. I wonder how many geneticists still read Fisher during their training. I can tell you this: the bound volume of the Proceedings of the Royal Society of Edinburgh in our library didn’t look like it’s been picked up for 30 years. I mean, serious dust on the cover.

I wrote last month about how Fisher invented “variance”, and noted the very useful property that the variance is a sum of contributions from different causes. It seems remarkable that Fisher could arrive at statistical framework for identifying the interactions of multiple genes on a trait, at a time when only a relative handful of “Mendelian factors” had yet been found.

Now that we are able to find Mendelian factors in whole-genome association studies, it’s remarkable that Fisher’s framework is so often forgotten!

References:

Fisher RA. 1918. The correlation between relatives on the supposition of Mendelian inheritance. Proc R Soc Edinburgh 52:399-433.