Although blue is the second-most common eye color worldwide, it is still relatively uncommon, only seen in around 8 to 10% of people. But that percentage becomes all the more impressive when you consider how young this trait is among humans.
All blue eyes today can be traced back to a single common ancestor that spontaneously developed the mutation for this eye color, according to researchers at the University of Copenhagen (UoC). The mutation spread from this ancestor across the globe over the last 6 to 10 millennia.
"Originally, we all had brown eyes," said lead author Professor Hans Eiberg from the UoC Department of Cellular and Molecular Medicine. "But a genetic mutation affecting the OCA2 gene in our chromosomes resulted in the creation of a switch which literally turned off the ability to produce brown eyes."
For the study, the team used genetic material from the Copenhagen Family Bank belonging to three generations of people of Danish descent to identify the genetic mutation that results in blue eyes. Only families that included members who had blue and brown eyes were used in the study (both parents and offspring), and families whose irises show blue- and green-spot segregation were excluded; all in all, 100 families were included in the analysis. Out of these, 45 families had at least one individual with brown eyes, and 55 were composed exclusively of blue-eyed members. Two individuals born with heterochromia (who have eyes of different colours) were also included in the analysis. Genetic material from individuals from Turkey and two from Jordan was also used in the study.
Each participant filled out a questionnaire asking them to determine their own eye color from four categories -- brown, blue, gray, and green --, whether brown spots or peripupillary rings were present on their irises, and what color their hair was (red, black, brown, or blonde) when they were between the ages of 20 and 30.
The team then examined the DNA and mitochondrial DNA of participants in order to determine the mutation that is most likely responsible for blue eyes. They found that this is a mutation that affects an allele known as the OCA2 gene.
The team explains that OCA2 genes encode the synthesis pathway for a so-called P protein. This compound is involved in the production of melanin inside the body -- the pigment that gives the colour of our hair, skin, and of the irises in our eyes.
The mutation that results in blue eyes doesn't completely turn off the production of melanin, however. The genetic 'switch' that the team mentions is located in genes adjacent to OCA2. Once switched, this genetic mechanism works only to reduce the amount of melanin secreted in the body, essentially diluting the pigmentation of the iris from hues of brown to shades of blue. If the OCA2 gene is completely inhibited in an individual, the team explains, they would completely lack pigmentation, resulting in the condition known as albinism.
There is significant variation in iris melanin levels within people with green and brown eyes, the team explains. However, blue-eyed individuals show very little variation in iris melanin levels between each other, the team explains. These differences are also notable in their genome: while there is considerable individual variation in the genes that encode melanin levels in people with brown or green eyes, blue-eyed individuals are very similar. This similarity, they say, suggests that all blue-eyed individuals share a common ancestor. Based on the study and comparison of the participants' mitochondrial DNA (which is inherited only on the maternal side and can be used to track the passing of generations in the genome), that common ancestor lived sometime between 6- to 10,000 years ago, they add.
The mutation that results in blue eyes is neither positive or negative, the team explains -- it confers no evolutionary advantage or disadvantage and doesn't impact an individual's chances of survival. In this, it resembles a host of other mutations affecting hair colour, baldness, freckles, or those producing 'beauty marks'.
"[Such a mutation] simply shows that nature is constantly shuffling the human genome, creating a genetic cocktail of human chromosomes and trying out different changes as it does so," says Professor Eiberg.
The paper "Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression" has been published in the journal Human Genetics.