Friday, February 8, 2008

What causes two different colored eyes?

In the context of discussing pedigrees, some great questions were asked in class concerning the inheritance of eye color: "Why do some people's eyes change color?" "Why is it common for some dogs to have two different colored eyes - one blue, one brown?" and "What are the genes that code for eye color anyway?"

Let's start with the basic genetics first. Color in your body, regardless of whether it's in the skin, hair, or eyes, is caused by the production of melanin. Melanin is a dark pigment produced by special cells called melanocytes. Within these cells are special organelles that actually product the melanin. What determines color is not how many of these organelles are present, but rather their activity levels. With the exception of albinos (people who have inherited two faulty copies of the genes for melanin production), we all have melanin producing cells, but some produce more melanin than others, resulting in darker hair, eyes, or skin.

Genetics of Eye Color

Eye color isn't a simple one-gene-locus-two-allele system like the conditions we've been discussion so far. In fact, scientists aren't entirely sure which genes are involved in eye color, but a recent paper just published seems to have located one gene that may be involved in making eyes blue or brown (called OCA2). There is almost certainly another gene that codes for green or blue eyes (called gey). What do these genes do? They tell the cells in the stroma of the iris (the part that actually has color!) to make melanin. If the OCA2 gene is working properly, lots of melanin is made, and you get brown eyes. If you have one working OCA2 gene and one broken gene, melanin still gets made. It takes inheriting two nonworking copies of OCA2 to get blue eyes. It appears that this mutation causing improperly functioning OCA2 probably popped up in a person living about 6-10,000 years ago.

But wait, what about green eyes? Well, we have to take into account what's going on with that gey gene too. It probably works like this: Let B = functional OCA2, and b = nonfunctional OCA2. Let G = functional gey, and b = nonfunctional gey. Remember, G makes eyes green. The two genes work together to produce pigments for the eyes. Take a look at how this is likely to occur with the table below relating genotypes to phenotypes.

BB bb = Brown
BB Gb = Brown
BB GG = Brown
Bb bb = Brown
Bb Gb = Brown
Bb GG = Brown
bb GG = Green
bb Gb = Green
bb bb = Blue

Notice that both B and G are dominant to b, but B is dominant to G. (See this post from Ask a Geneticist for more about how this works).

How to get two different colored irisis (Heterochromia Iridis)
Having two differently colored eyes is fairly rare in humans (there are a few famous cases, like David Bowie and Keiffer Sutherland), but more common in dogs and cats. How does this happen? Basically, something goes wrong and one iris does not get the "signal" to turn its melanin production on. Trauma is a pretty common cause for this - which accounts for David Bowie's heterochromia (he was hit in a fight). So the genes are still there, they just aren't getting the signals to function anymore. If trauma occurs during development, the specialized pigment cells, melanocytes, may die off and not be replaced.

Another way is to have a condition which prevents the melanocytes from migrating to the right place. Waardenburg's is a well known condition in which this happens. There are 4 genes responsible for this syndrom, and they control for development of the face and ears, among other things. If these genes aren't functioning properly, melanocytes that are produced in the fetus don't get the proper directions to migrate into the eyes, or even into hair follicles. People with this condition also usually have a lock of white hair and hearing loss. It turns out that because of inbreeding in dogs, Waardenburg's is fairly common, hence the typical association of different colored eyes and hearing loss in dogs.

Last, but perhaps most intriguing, is the possibility that one has two different functioning genes in each eye. There are two ways this can happen: Mosaicism and Chimerism. I had guessed in class that mosaicism may be responsible: this is when a gene mutates (a mistake occurs during DNA replication) early on in development. All the mitotic daughter cells of that mutated cell will also contain the mutation, but other cells will still have the normal gene. Hence, the body contains a "mosaic" of cells with normal genes and with mutated genes. Sounds weird, but it's extremely common - in fact, we're all mosaics! Our body has trillions of cells, and every time they divide, there's a chance for mistakes in replication. Some environmental factors can actually cause mutations, like sunlight or chemicals. But even so, mutations are pretty rare, and there'd be only a few mutated cells in your body at any one time.

Chimerism is really fascinating, and pretty rare: this is when the cells of two different people fuse! So a chimera is actually two people's DNA in one body! How can this occur? If a mother releases two eggs instead of one at a time, and both are fertilized by dad's sperm, you normally get two different people developing - fraternal twins. Occasionally, those two fertilized eggs (zygotes) will fuse into one, but both sets of DNA are still there. Because this happens so early in development, for the most part, the slight differences in DNA won't cause big differences in the person's body parts (one leg won't be significantly longer than the other!) since the cells are being coordinated with the same signals. A very famous case involving chimerism and paternity disputes can be read here.

For more information, try these:

about heterochromia iridis:

OCA2 in the news:

Mosaicism and Chimerism:

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