Is there a difference between the terms “molecular epistasis” and “genetic epistasis”? Many worm papers seem to use these terms
synonymously, but some papers use the phrase “genetic and molecular epistasis” which to me implies that they are not the same
thing. I am asking because I am trying to understand a comment: “You are relying heavily on molecular epistasis with very little use
of genetic epistasis.” Please point me toward a source that explains how to use the term “molecular epistasis” correctly. Thanks.
For interpreting a finding of epistasis in pathway construction, you sometimes see two alternative interpretations that I’ve seen called “biochemical epistasis” and “regulatory epistasis”, and these might be relevant to the point at issue:
For purposes of illustration, let’s say you’ve got two genes, gene-1 and gene-2, with null mutations in each, distinguishable phenotypes, and gene-1(null) is epistatic to gene-2(null) (the double mutant looks like gene-1(null) rather than like gene-2(null) or a combination). Let’s say the readout is color: wild-type is pink, the gene-1(null) mutant is white, and the gene-2(null) mutant is red.
The more commonly encountered interpretation would be the regulatory (or “genetic”?) one, in which gene-2 acts on gene-1, something like so:
gene-2 —| gene-1 —> conversion of white substrate to red pigment
In this pathway, loss of gene-2 causes a level of gene-1 activity higher than in the wild type, but has no effect if there is no gene-1 to have its activity increased.
Alternatively, you could have a biochemical (“molecular”?) pathway in which a substrate is modified by the product of gene-1 to form an intermediate product that then acts as a substrate for the product of gene-2. Thus, in the gene-1(null) mutant or in the double mutant the first substrate would accumulate, while in the gene-2(null) mutant the intermediate product would accumulate. This pathway could take the following form:
white substrate --[GENE-1]–> red intermediate --[GENE-2]–> pink pigment
As you can see, the same set of data gives very different pathways if interpreted in these different ways. And, of course, the term epistasis gets used in still more confusing ways. Whether this reply is actually relevant to your situation, however, is quite beyond me. Couldn’t you ask for clarification?
I have seen ‘molecular epistasis’ used to mean an interaction between two genes inferred from a molecule-based assay. For example, (circa 1986) in the Drosopihla embryo, in situ hybridization assay of engraied expression in various mutant embryos was used to infer that engrailed was regulated by pair rule genes.
-Paul Sternberg (I will change my user name to not be initials at some point)