Eye color is a polygenic phenotypic character and is determined by the amount and type of pigments in the eye's iris.

Humans and animals have many phenotypic variations in eye color, as blue, brown, green and others. These variations constitute phenotypic traits.

The genetics of eye color are complicated and eye color is determined by multiple genes. Some of the eye color genes include EYCL1 (a green/blue eye color gene located on chromosome 19), EYCL2 (a brown eye color gene) and EYCL3 (a brown/blue eye color gene located on chromosome 15). The once-held view that blue eye color is a simple recessive trait has been shown to be wrong. The genetics of eye color are so complex that almost any parent-child combination of eye colors can occur.

In human eyes, these variations in color are attributed to varying ratios of eumelanin produced by melanocytes in the iris. The brightly colored eyes of many bird species are largely determined by other pigments, such as pteridines, purines, and carotenoids.

Three main elements within the iris contribute to its color: the melanin content of the iris pigment epithelium, the melanin content within the iris stroma, and the cellular density of the iris stroma. In eyes of all colors, the iris pigment epithelium contains the black pigment, eumelanin. Color variations among different irises are typically attributed to the melanin content within the iris stroma. The density of cells within the stroma affects how much light is absorbed by the underlying pigment epithelium. OCA2 gene polymorphism, close to proximal 5′ regulatory region, explains most human eye-color variation.

Genetic determination of eye color

Eye colours can range from the most common colour, brown, to the least common, green. Rare genetic mutations can even lead to unusual eye colours: black, red, or the appearance of violet. Eye colour is an inherited trait influenced by more than one gene. These genes are being sought using associations to small changes in the genes themselves and in neighboring genes. These changes are known as single nucleotide polymorphisms or SNPs. The actual number of genes that contribute to eye color is currently unknown, but there are a few likely candidates. A study in Rotterdam (2009) found that it was possible to predict the color of eyes with more than 90% accuracy for brown and blue, using just six SNPs (from six genes).

The gene OCA2 ( ), when in a variant form the gene causes the pink eye color and hypopigmentation common in human albinism. (The name of the gene is derived from the disorder it causes, oculocutaneous albinism type II.) Different SNPs within OCA2 are strongly associated with blue and green eyes as well as variations in freckling, mole counts, hair and skin tone. The polymorphisms may be in an OCA2 regulatory sequence, where they may influence the expression of the gene product, which in turn affects pigmentation. A specific mutation within the HERC2 gene, a gene that regulates OCA2 expression, is partly responsible for blue eyes. Other genes implicated in eye color variation are: SLC24A4 and TYR.

Blue eyes with a brown spot, green eyes and gray eyes are caused by an entirely different part of the genome. As Eiberg said: "The SNP rs12913832 [of the Herc2 gene] is found to be associated with the brown and blue eye color, but this single DNA variation cannot explain all the brown eye color variation from dark brown over hazel to blue eyes with brown spots."

Classification of colors

Iris color can provide a large amount of information about an individual and a classification of various colors may be useful in documenting pathological changes or determining how a person may respond to various ocular pharmaceuticals. Various classification systems have ranged from a basic light or dark description to detailed gradings employing photographic standards for comparison. Others have attempted to set objective standards of color comparison.

As the perception of color depends on viewing conditions (e.g., the amount and kind of illumination, as well as the hue of the surrounding environment), so is the perception of eye color.

Eye colors range from the darkest shades of brown to the lightest shades of blue. To meet the need for standardized classification, at once simple yet detailed enough for research purposes, Seddon et al. developed a graded system based on the predominant iris color and the amount of brown or yellow pigment present. There are three pigment colors that determine, depending on their proportion, the outward appearance of the iris: brown, yellow, and blue. Green irises, for example, have blue and some yellow. Brown irises contain mostly brown. Eye color in animals other than Homo sapiens are differently regulated. For example, instead of blue as in humans, autosomal recessive eye color in the skunk Corucia zebrata is black, and the autosomal dominant color is yellow-green.

Changes in eye color throughout life

In European populations, children are most commonly born with unpigmented (blue) eyes. As the child develops, melanocytes, cells found within the iris of human eyes (as well as skin and hair follicles) slowly begin to produce melanin. Because melanocyte cells continually produce pigment, eye color, in theory, can be changed.

Changes (lightening or darkening) of eye colors during puberty, early childhood, pregnancy, and sometimes after serious trauma (like heterochromia), do represent cause for plausible argument to state that some eyes can or do change, based on chemical reactions and hormonal changes within the body. Most eye changes happen when the infant is around one year old, although it can happen up to 3 years of age.

Studies on Caucasian twins, both fraternal and identical, have shown that eye color over time can be subject to change, and major demelanization of the iris may also be genetically determined. Most eye color changes have been observed or reported in the Caucasian population with hazel eyes.

Eye color chart (Martin-Schultz scale)

Carleton Coon created this chart by the Martin-Schultz scale often used in physical anthropology.

1. Light eyesEyes light and light mixed are 16-12 in Martin scale.

   Light: Grey, blue, green.

   Light-mixed:

   1. Very light-mixed (blue with grey or green or green with grey)
   2. Light-mixed (light or very light-mixed with small admixture of brown pigment)
2. Mixed eyes

   Mixed: 12-6 in Martin scale. Mixture of light eyes (blue, grey or green) with brown pigment when light and brown pigment are the same level.

3. Dark eyes

   Dark-mixed: 6-4 in Martin scale. Brown with small admixture of light pigment.

   Dark: 4-1 in Martin scale. Brown (light brown and dark brown) and very dark brown (almost black).

Amber

Amber eyes are of a solid color and have a strong yellowish/golden and russet/coppery tint. This might be due to the deposition of the yellow pigment called lipochrome in the iris (which is also found in green and violet eyes). Amber eyes should not be confused with hazel eyes; although hazel eyes may contain specks of amber or gold, they usually tend to comprise many other colors, including green, brown and orange. Also, hazel eyes may appear to shift in color and consist of flecks and ripples; while amber eyes are of a solid gold hue.

The eyes of some pigeons contain yellow fluorescing pigments known as pteridines. The bright yellow eyes of the Great Horned Owl are thought to be due to the presence of the pteridine pigment xanthopterin within certain chromatophores (called xanthophores) located in the iris stroma. In humans, yellowish specks or patches are thought to be due to the pigment lipofuscin, also known as lipochrome.

Blue

In 2008, new research revealed that people with blue eyes have a single common ancestor. Scientists tracked down a genetic mutation that leads to blue eyes. The mutation occurred between 6,000 and 10,000 years ago; researchers state that before then, blue eyes did not exist. "Originally, we all had brown eyes", said Hans Eiberg from the Department of Cellular and Molecular Medicine at the University of Copenhagen. The mutation affected the OCA2 gene, which is involved in the production of melanin, the pigment that gives color to our hair, eyes and skin. Eiberg stated, "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:

The genetic switch is located in the gene adjacent to OCA2 and rather than completely turning off the gene, the switch limits its action, which reduces the production of melanin in the iris.

In effect, the turned-down switch diluted brown eyes to blue.

If the OCA2 gene had been completely shut down, our hair, eyes and skin would be melanin-less, a condition known as albinism.

Blue eyes contain low amounts of melanin within the iris stroma; longer wavelengths of light tend to be absorbed by the underlying iris pigment epithelium, and shorter wavelengths are reflected and undergo Rayleigh scattering. The type of melanin present is eumelanin. The inheritance pattern followed by blue eyes is considered similar to that of a recessive trait (in general, eye color inheritance is considered a polygenic trait, meaning that it is controlled by the interactions of several genes, not just one). Eiberg and colleagues showed in a study published in Human Genetics that a mutation in the 86th intron of the HERC2 gene, which is hypothesized to interact with the OCA2 gene promoter, reduced expression of OCA2 with subsequent reduction in melanin production. The authors concluded that the mutation may have arisen in a single individual in the Near East or around the Black Sea region 6,000-10,000 years ago during the Neolithic revolution.

Blue eyes are most common in Northern Europe and Central Europe and to a lesser degree in Southern Europe, North America and southern Central Asia; Afghanistan is a notable example. They're also found in parts of North Africa, West Asia, and South Asia, in particular the northern areas of India and Pakistan.It can rarely occur as far south as Sri Lanka. Moreover, blue/green/gray eyes can be found within the population of East Asia, especially among Chinese, even Han Chinese,[73673], allegedly due to the constant wars and raids between Chinese Empire and Indo-European Turk nomads from Eurasia Steppe . Those conflicts could result in tens of thousands of people, mainly women and children, being captured and brought back to the victor's society. There are few scientific studies of light-color eyed Han Chinese.

A 2002 study found the prevalence of blue eye color among Caucasians in the United States to be 33.8 percent for those born from 1936 through 1951 compared with 57.4 percent for those born from 1899 through 1905. Blue eyes have become increasingly rare among American children with only 1 out of every 6 – 16.6 percent which is 49.8 million out of 300 million (22.4% of white Americans) of the total United States population having blue eyes. The plunge in the past few decades has taken place at a remarkable rate. A century ago, 80 percent of people married within their ethnic group. Blue eyes were routinely passed down, especially among people of Western and Northern European ancestry. In the 1930s, eugenicists used the disappearance of blue eyes as a rallying cry to support immigration restrictions. They went so far as to map the parts of the country with the highest and lowest percentage of blue-eyed people.

The outer surface of the iris of a blue eyed person is actually clear, lacking the outer layer of pigmentation that is found in brown eyes. Their color is caused by the inner layer of pigmentation and the semi-opaque fibrous tissues which lay between the two layers.

Brown

Brown eyes are dominant in humans and, in many parts of the world it is nearly the only iris color present. It is less common in countries around the Baltic Sea and in Scandinavia. Dark pigment of brown eyes are most common in East Asia , Africa and the Americas. In humans brown eyes contain large amounts of melanin within the iris stroma, which serves to absorb light at both shorter and longer wavelengths. Brown eyes are the most common eye color, with over half of the world's population having them.

Gray

Gray eyes have less melanin than blue eyes, even though they are considered a darker shade of blue (like blue-green). Gray eyes are most common in European Russia, Finland and the Baltic States . It can also be found to a lesser extent in parts of India. Under magnification, gray eyes exhibit small amounts of yellow and brown color in the iris. Ultimately there are at least two things that could determine gray eye color. The first is the amount of melanin made and the second is the density of the proteins in the stroma.

A gray iris may indicate the presence of a uveitis. However, other visual signs make a uveitis obvious. Gray iris color, as well as blue, are at increased risk of uveal melanoma.

Visually, gray eyes often tend to appear to change between the shades of blue, green and gray; this is because gray eyes are extremely light, as mentioned before. The color change for gray eyes is usually influenced by the lighting and the colors in the surroundings (such as clothes, makeup, etc.).

Green

Green eyes are the product of low to moderate amounts of melanin and probably represent the interaction of multiple variants within the OCA2 and in other genes. Green eyes are most common in Northern and Central Europe. They can also be found in parts of South Asia, West Asia, and North Africa. In Iceland, 89% of women and 87% of men have either blue or green eye color. A study of Icelander and Dutch adults found green eyes to be much more prevalent in women than in men. Among European Americans, green eyes are most common among those of Celtic and Germanic ancestry, about 16%.

Hazel

Hazel eyes are due to a combination of Rayleigh scattering and a moderate amount of melanin in the iris' anterior border layer. Hazel eyes often appear to shift in color from a light brown to a dark golden-green. A number of studies using three-point scales have assigned hazel to be the medium-color between the lightest shade of blue and darkest shade of brown. Hazel mostly consists of Brown and Green. The dominant color in the eye can either be green or light brown/gold. This can sometimes produce a multicolored iris, i.e., an eye that is light brown/amber near the pupil and charcoal or dark green on the outer part of the iris (and vice versa) when observed in sunlight. Hazel is commonly found in Europe, the Middle East, Americas, Central Asia, and parts of South Asia.

Definitions of the eye color hazel vary: it is sometimes considered to be synonymous with light-brown or gold, as in the color of a hazelnut shell. In North America, hazel is often used to describe eyes that appear to change color.

Red

The eyes of people with albinism may appear red under certain lighting conditions owing to the extremely low quantities of melanin, allowing the blood vessels to show through.

Medical implications

Those with lighter iris color have been found to have a higher prevalence of age-related macular degeneration (ARMD) than those with darker iris color; lighter eye color is also associated with an increased risk of ARMD progression. An increased risk of uveal melanoma has been found in those with blue, green or gray iris color. Additionally, an August 2000 study suggests that people with dark brown eyes are at increased risk of developing cataracts, and therefore should protect their eyes from direct exposure to sunlight.

Eye color may also be symptomatic of disease. Aside from the iris, yellowing of the whites of the eyes is associated with jaundice and symptomatic of liver disease, including cirrhosis, hepatitis and malaria.

Aside from the above factors, yellowing of the whites of the eyes in people with darker pigmented skin is often due to melonin being present in the whites of the eyes. However, any sudden changes in the color of the whites of the eyes should be addressed by a medical professional.

Anomalous conditions

Aniridia

Aniridia is a congenital condition characterized by an extremely underdeveloped iris which appears absent on superficial examination.

Ocular albinism and eye color

Normally, there is a thick layer of melanin on the back of the iris. Even people with the lightest blue eyes, with no melanin on the front of the iris at all, have dark brown coloration on the back of it, to prevent light from scattering around inside the eye. In those with milder forms of albinism, the color of the irises is typically blue, but can vary from blue to brown. In severe forms of albinism, there is no pigment on the back of the iris, and light from inside the eye can pass through the iris to the front. In these cases, the only color seen is the red from the hemoglobin of the blood in the capillaries of the iris. Such albinos have pink eyes, as do albino rabbits, mice, or any other animal with total lack of melanin. Transillumination defects can almost always be observed during an eye examination due to lack of iridial pigmentation. The ocular albino also lacks normal amounts of melanin in the retina as well, which allows more light than normal to reflect off the retina and out of the eye. Because of this, the pupillary reflex is much brighter in the albino, and this can increase the red eye effect in photographs.

Heterochromia

Heterochromia (also known as a heterochromia iridis or heterochromia iridium) is an ocular condition in which one iris is a different color from the other iris (complete heterochromia), or where the part of one iris is a different color from the remainder (partial heterochromia or sectoral heterochromia). It is a result of the relative excess or lack of pigment within an iris or part of an iris, which may be inherited or acquired by disease or injury. This uncommon condition usually results due to uneven melanin content. A number of causes are responsible, including genetics such as chimerism, Horners Syndrome and Waardenburg syndrome. A common cause in females with heterochromia is X-inactivation, which can result in a number of heterochromatic traits, such as calico cats. Trauma and certain medications, such as some prostaglandin analogues can also cause increased or decreased pigmentation in one eye. On occasion, the condition of having two different colored eyes is caused by blood staining the iris after sustaining injury.

See also

• Iridology
• Hair color
• Human skin color
• Xanthophore
• List of Mendelian traits in humans

References

External links

• Genetics of eye color
• Eye Color and Human Diseases
• Various links on human eye color