Can you explain the genetics of an individual with one blue eye and one brown eye?

June 28, 2007

A curious adult from Tennessee asks:

"I read an article on this site that said 'Blue eyes are caused by changes in the OCA2 gene' and found it extremely interesting. I have another combination to throw into the mix. Can you explain the genetics of an individual with one blue eye and one brown eye? David Bowie is one of these individuals."

Great question. Different colored eyes are pretty rare in people, although it is more common in some animals. For example, dogs like Siberian Huskies, cats, and horses often have different colored eyes.

But this sort of thing obviously happens in people too. Some are even famous like Christopher Walken or Kiefer Sutherland.

Different colored eyes, or heterochromia, comes about differently than other eye colors. It tends to happen when something has gone a bit wrong in making eye color. Or if the body happens to shut off a gene in only some cells of the body (Click here to learn more about this possibility.)

Heterochromia can be the result of too much or too little pigment in the iris (or part of the iris) of one eye. This can be because of genetics, disease, or injury.

Eye color and melanocytes

See, eye color usually comes from the amount of pigment in the front part of the iris of the eye (called the stroma). Little or no pigment gives blue eyes, some pigment gives green and lots of pigment gives brown eyes.

The pigment is actually made in special cells called melanocytes. If anything happens that affects the health of the melanocytes in an eye, then that eye will look blue. No melanocytes means little or no pigment which means blue eyes.

Puppy with heterochromia
If melanocytes don’t migrate to a certain area during development, that area will not have pigment, causing white spots or light-colored eyes. (Image: Wikimedia Commons)

Another way to end up with different colored eyes is if each eye has a different set of eye color genes. This isn't that common but we'll go over it as well.

So how can one eye end up without any melanocytes? There are a number of ways that all have to do with how sensitive a melanocyte is.

Once melanocytes are made in a developing fetus, they need to migrate to the right spots such as skin and eyes. If something affects their growth or their ability to travel, then they can die off.

To end up happily making pigment in the right place, melanocytes need a variety of signals from other cells. This network of cells is pretty easily disrupted. If anything happens during development to disturb the melanocytes in their migration to just one eye, the result could be someone with a different colored left and right eye.

Genetic Conditions

Disruptions during development are not the only way to keep melanocytes from traveling and/or surviving. Another way is if someone has something called Waardenburg syndrome.

People with Waardenburg syndrome have mutations in certain genes that cause some melanocytes to get lost on their way to where they are supposed to go. This means that people with Waardenburg syndrome can end up with an eye that didn't get any melanocytes (and so is blue). Or a patch of hair or skin that ends up white because melanocytes couldn't find their way there. 

Sometimes someone can end up with one eye that has two different colors. Because some melanocytes made it to the right place and some didn't. 

There are changes in several genes that can cause Waardenburg syndrome. Mutations in any one of them will disrupt the normal development of melanocytes. This isn't surprising given how complex it is to make a cell and have it travel to the right spot. Something that complicated is going to be controlled by lots of genes. 

So lost or destroyed melanocytes explains a lot of heterochromia. But probably not all of it. 

Child with heterochromia
This child’s heterochromia is caused by Waardenburg Syndrome. (Image: Wikimedia Commons)

Genetic Chimerism and Mosaicism

Another possibility is if each eye has a different set of eye color genes. There are a couple of ways this could happen.

Let's focus on the OCA2 gene for this. OCA2 is a key eye color gene. Certain versions of this gene make lots of pigment and so lead to brown eyes. Other versions make no pigment and lead to an eye color other than brown. (These other versions don't necessarily give blue eyes because there are other eye color genes besides OCA2 -- click here to learn more).

So one way that someone could end up with different colored eyes is if the OCA2 genes were different in each eye. For example, imagine that the right eye has a brown version of OCA2 and so is brown. And that the left eye does not have a brown version and so is green or blue.

As I said, there are a couple of ways this could happen. One is something called chimerism. This is essentially where two fertilized eggs fuse together to create a single person. If each fertilized egg has a different set of eye color genes, then a chimera can end up with two different colored eyes (click here to learn more about chimerism).

The other way is something called mosaicism. What happens is that a gene gets changed early on in a single cell. All cells that develop out of that mutated cell are now subtly different from the rest of the cells in the body. If that subtle difference is in an eye color gene, then you may end up with two different colored eyes (click here  to learn more).

Both of these conditions result in each eye possibly having a different set of eye color genes. And so result in a person with two different colored eyes.

However, neither of these scenarios are as common as damaged melanocytes. And there are other ways to end up with different colored eyes too.

Eye Injury

Sometimes deposition of foreign material or blood as a result of injury to the eye can cause an iris to look darker. And sometimes the use of certain eye drops can stimulate the melanocytes to make more pigment. Both of these can explain some cases of heterochromia.

So, have we explained David Bowie's eyes yet? Believe it or not, no.

We know his eye color is the result of a barroom fight. But the injury didn't affect melanocytes or deposit blood in the iris. Instead, his eye color change comes from a permanently enlarged pupil that makes his eye look dark.

David Bowie
One of David Bowie’s eyes appears darker than the other because of a permanently enlarged pupil. (Image: Flickr)

The size of the pupil is controlled by muscles in the iris. The muscles are controlled by nerves from the brain to the eye. Damage to the nerve that normally constricts the pupil produces an abnormally large pupil.

I don't know the explanation for the other famous people I brought up earlier. Nor do I know why actress Kate Bosworth has one blue eye and one hazel eye. Or why lead singer Tim Mcllrath of Rise Against has one brown eye and one blue eye. Or why actress Jane Seymour has one brown eye and one green eye. But we've learned there are lots of ways to end up with this rare condition.

Some are genetic like Waardenburg syndrome or chimerism and mosaicism. And some are the result of injury either in the womb or, as in the case of David Bowie, in a bar. 


Author: Dr. Azita Alizadeh

When this answer was published in 2007, Azita was a postdoctoral fellow in the Department of Genetics, studying the genetics of cat and hamster pigmentation in Greg Barsh’s laboratory. Azita wrote this answer while participating in the Stanford at The Tech program.

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