Eye color happens because of the amount of the pigment melanin found in the eye. Not anywhere in the eye but in a very special place, the stroma of the iris.
Lots of melanin here gives brown eyes and less melanin gives green. Little or no melanin in the stroma of the iris gives blue eyes.
In terms of eye color, OCA2 comes in two versionsbrown (B) and blue (b). The brown version works in the stroma, the blue version does not. Since the blue version doesn't work there, no melanin builds up. So these folks have blue eyes.
Now OCA2 isn't just involved in eye color. When it is completely broken, we end up with something called P-gene related oculocutaneous albinism. This is a form of albinism more common in Africans than in Caucasians.
So to have blue eyes without albinism, OCA2 has to work everywhere except the stroma. The new paper identifies DNA changes that presumably do this to the OCA2 gene.
But how can a DNA change cause a gene to work in some places but not in others? By affecting whether a cell can read the gene or not.
A gene really is just a recipe for making a protein. Just like a real recipe, if no one reads it and follows the directions, nothing gets made. So cells need to read a gene for it to have any effect.
The first step in reading a gene is finding it. This might seem silly until we remember that only 2-3% of our DNA is genes. The cell can't waste its precious energy reading all of this DNA. So it has devised a way to find the start of genes.
The start of a gene is marked in a certain way, sort of like sentences are when we write. In English, we know where a sentence starts because it starts with a capital letter and comes after a period (or exclamation point or question mark). The same sort of thing is true in cells.
Not punctuation and capital letters, of course. But the start of a gene is marked. One way a cell marks a gene is to plop some proteins on the DNA nearby. These proteins tell the cell where the start of a new gene is.
And different kinds of cells have different sets of proteins. That is what makes a lung cell different from a muscle cell. Or the stroma different from the rest of the eye.
One type of protein that can vary from cell to cell is the kind that marks the start of a gene. So the stroma might have a different marker protein for OCA2 than the rest of the cells of the body.
This is sort of like the different ways different languages have to mark the start of a sentence. In English, the start of a question is a capital letter. In Spanish, it is an upside down question mark and a capital letter.
But why do changes in the DNA affect these marker proteins? Because the marker proteins know where to sit based on the DNA.
Let's say there is a gene X. At the start of gene X is a series of DNA letters that looks like this:
Now there is a protein found in the stroma that likes to sit on AGTC. There is one of these in front of gene X so the protein sits there. This protein tells the cell that this is a gene and to start reading.
Now imagine that someone has this DNA in front of gene X:
Now our protein has nowhere to sit and so is not in front of gene X. The result is that the cell doesn't recognize the start of gene X anymore so gene X is not turned on in this cell.
But this change would not affect another protein that likes GACTG. It can still sit on the DNA and mark the gene for the cell. So any cell that has this protein could still turn gene X on.
This is presumably what is happening with OCA2 and blue eyes. The 3 identified changes are outside of the part of the gene that is read. So the changes may cause a protein in the stroma to no longer sit on the DNA. Now the machinery in the stroma cells doesn't see the gene and you have blue eyes.
This is at least the theory. The next step will be to show how the gene isn't being read in the stroma. Stay tuned.