Simplified Explanation:

Labradors come in three different colors due to two different genes. In this lesson, find out how epistasis works as one phenotype is controlled by the products from
two or more genes.

Exceptions to your day are just a part of life. I'm sure there are times in your day when you say to yourself, 'Well, I was going to do this but then this other thing
happened and now my plans are changed,' right? It probably happens a lot; what happens at the beginning of your day will affect what happens at the end of your day.
This cause and effect is a normal part of life. In this lesson, we're going to talk about a genetic concept that involves occasions when the phenotype of one gene
depends on a second gene because these two genes control a common phenotype.

To better understand what we're about to discuss, let me tell you a story. You are out of milk. This is a problem, because you need milk in your coffee. So you decide
to head out to the store and buy some. Simple enough, right? But to get to the store you need to do a few things first. First, you need to get your keys. Second, you
need to drive your car to the store. And next, you need to buy the milk.

Now, let's say you can't find your keys. Ugh. So if you can't find your keys, this makes it impossible to start your car and then you can't go to the store to get your
milk. Your car is in the driveway; it's ready to go, but you are keyless. Therefore, you don't end up getting any milk.

In genetics, epistasis occurs when two or more different gene loci contribute to the same phenotype, but not additively. Epistasis is often described as occurring when
one gene locus masks or modifies the phenotype of a second gene locus. The term epistatic describes the relationship between the genes in epistasis.

In our out-of-milk example, we can think of having milk as the final phenotype. There are actually three things that need to happen that influence having milk, which
are like our 'genes' in epistasis. These are epistatic to each other. First, we have to find our keys. Second, we have to drive our car to the store, and third we need to
buy the milk. If the first step never happens because there was a mistake (in this scenario, we can't find our keys - so we can call this a mutation) then the second step
and anything after it also cannot happen. Therefore, the mutation in the first step masked or modified the second step from ever happening. No milk in your coffee this
morning!

Epistasis Examples

Epistasis can occur in scenarios other than a step-wise progression, but this is the most common example. Another way to look at this is that a product, like coat color
in some animals, is controlled by a pigment (P). Different genes contribute to the steps needed to make P from a precursor molecule. In order to get to P, all these
steps have to be fully functional. If there is a mutation in one of these genes, the reaction cannot take place and the phenotype, or in this case, the production of
pigment resulting from coat color, is affected.

Another common epistatic interaction between genes can occur when two genes produce proteins that have the same role. In this case, a precursor is converted by two
different gene products into a phenotype of colored wheat kernels. Here, if there is a mutation in one gene so that the resulting protein wasn't functional, the other
protein from the second gene could take over. However, if you have mutations in both genes so that both were not functional, the wheat kernels are colorless. Here,
mutations in both genes would modify the phenotype of color, making this another example of epistasis.

Epistasis in Coat Color

I started this lesson by saying that life is full of exceptions. I'd like to show you that epistasis is an example of why you might get an exception to a basic genetic
principle.

You've probably seen, petted, or even owned a Labrador before. These dogs come in three colors: Black, chocolate brown, and yellow. The color behind these dogs'
coats is due to epistasis.

An Analogy for Genes Working Together

Like workers in an assembly line, proteins work together to carry out processes.

Epistasis involves not genes so much as the proteins they code for. (So do dominant and recessive, for that matter.) Genes with epistatic relationships tend to code for
proteins that work together in the same processes. An analogy might be easier to understand.

Lets say workers A, B, and C carry out the steps for painting a design on a poster. Like genes, a, b, and c are the instructions.
Worker A puts paint into the tray; a tells it how.
Worker B adds dye to the paint; b tells it what color.
Worker C paints a design on the poster; c tells it what design.

If we put ourselves in a position like that of researchers trying to learn about a genetic pathway, the instructions and the workers would be invisible. The only part of
the process that we would get to see is the output: the poster, which is like the phenotype.

Now imagine how different versions of the instructions would change the output. For example, b could say to add red dye. From looking at the output, we can tell that
the instructions for B have changed. Add blue and add red are like different alleles of b. And if a version of c said to draw a square, we could start to figure out
that color and shape are controlled by different instructions.

This is not epistasis (well get to that soon). Its genes working together to control an output.

Adding Epistasis

This version of a is epistatic to b and c: it hides their output.

This version of c is epistatic to a and b: it hides their output.

Epistasis typically applies to a certain allele, or version, of a gene. Epistasis depends on how the protein allele codes for actually functions. In our analogy, epistasis
depends on what the workers do in our process.

Now well add epistasis to our example. Lets say a version (or allele) of a is broken so that it contains no instructions. Worker A wouldnt be able to put paint into the
tray, and we would end up with a blank postereven though workers B and C are still doing their jobs.

This broken version of a is epistatic to b and c: the final product (a blank poster) shows no evidence of what B and C have been told to do. We cant tell if Bs
instructions said to add red or blue, or if Cs said to draw a circle or a square.

The important aspect of epistasis is that it doesnt just influence the phenotype, it hides the output of another gene or genes.

Now lets imagine that a is working, but c is broken. This version, or allele, of c is epistatic to a and b: the output shows no evidence of what A and B are doing.
Even though the output is again a blank poster, the cause is different than when a was broken.

Because of its role in the process, no allele of b can be epistatic to a or c . Changing the color of the dye, or even adding no dye at all, cannot hide what workers A and
C are doing.

Epistasis in Pigeon Feather Color

Like in the analogy above, proteins often work together like workers in an assembly line to carry out the processes that make our bodies function. The instructions for
building proteins are found in genes. Differences in genes, which pass from parent to child, lead to differences in proteins. Different proteins make our cells and
bodies function differently. Its the foundation of individual variation.

Looking at epistatic relationships offers clues that help us understand how genes and proteins function. Feather color in pigeons is a great example. Making and
distributing feather pigments is a complex, multi-step process involving many proteins. Variations in these proteins generate a lot of diverse feather colors and
patterns. Pigeonetics touches on a few of these variations (including pattern, spread, color, recessive red, and dilute), but there are many more.

White feather color, for example, tends to be epistatic to other colors. White feathers have no pigments, and like in our analogy above, they can come about in many
different ways. In other words, white has multiple genetic causes.

White feather color can come about by breaking any one of a number of genes that control pigment production or distribution. If melanocytes are missing a protein
they need to migrate to the skin or mature, feathers will be white. Another way to make white is to disrupt a protein that carries out an early step in the melanin
assembly line.

The recessive red page describes the molecular interactions of some of the proteins involved in making melanin pigments.

This chart shows just some of the components involved in making melanin pigments in pigeon feathers. Variations in the proteins that carry out any of these steps can influence feather color.