The Molecular Basis of Epistasis PART 1

Written By Vaishnavi Kolluru

Thanks @selena for the article idea!!

Epistasis is a type of non-allelic inheritance, where two gene products interact to produce a new modified phenotype. They produce phenotypic ratios that sum to 16, similar to a dihybrid cross. However, the difference is that dihybrid crosses track the transmission of 2 genes that control different traits, while epistasis' 2 genes control one trait.

There are 6 kinds of epistasis: simple dominant, simple recessive, inhibitory dominant, duplicate dominant, duplicate recessive, and polymeric inheritance. I'll cover the first three kinds in this article, and the next three next week. Each kind of epistasis has a characteristic F2 generation ratio, and a logically-derivable molecular pathway to explain the pattern. If you can memorize/understand these, you'll be pretty good on most USABO-level epistasis questions. Note: in the images below, pretend the boxes are filled with the letters of a dihybrid cross. Here they are for your reference:

Also note: when I say "B_" it means BB or Bb (the underscore is a blank to denote unknown allele).

Also, gene products are the things that do the actions. Genes themselves don't do much in the context of epistasis. We assume recessive genes produce no product/nonfunctional product, while dominant genes produce a functional product that participates in the molecular interaction. There are probably exceptions to this, but eh. It's a good enough model to understand this concept.

1) Dominant Epistasis

12:3:1

AA or Aa masks any allele of B/b. The yellow boxes all have a dominant A, so whether B is dominant or not, it doesn't matter; we still get the yellow phenotype. Between the pink and green, however, the aa has no control over phenotype as it's recessive. So, aaB_ has the pink phenotype due to a dominant B, while aabb has the green phenotype due to a recessive b. 

The B gene codes for an enzyme converting the green compound to a pink product. The A gene codes for an enzyme converting any starter substance to yellow.

2) Recessive (Supplementary) Epistasis

9:3:4

Either recessive genotype masks the other's. aa masks B_, while bb masks A_. For aabb, one recessive genotype is "stronger" than the other. In the case of the image above, bb's masking dominates aa. 

This is called "supplementary" epistasis, as one gene supplements the other's function. In our case, gene B needs dominant gene A to create a wild-type yellow phenotype. However, when B doesn't have A's product, we get a pink phenotype. When B is not there at all, nothing can happen, so we have a blue phenotype (which is presumably the starter situation).

3) Inhibitory Dominant Epistasis

13:3

The inhibitory gene (in this case, gene A) turns any B gene phenotype into the recessive version (it inhibits the dominant version by inactivating/degrading the product of gene B). Any bb is already recessive, so the presence or absence of the inhibitory A gene product doesn't make a difference. 

So those are the first three (of six) kinds of epistasis. Stay tuned for part 2!

Here's some stuff to read:

Vaishnavi Kolluru
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