Eye color



Eye color is a polygenic phenotypic character and is determined by the amount and type of pigments in the eye's iris. Humans and other animals have many phenotypic variations in eye color, as blue, brown, gray, green, and others. These variations constitute phenotypic traits.

The genetics of eye color are complicated, and 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 incorrect. 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 irides 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 colors can range from the most common color, brown, to the least common, green. Eye color 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, 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 color
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 does the perception of eye color.

Eye colors range from the darkest shades of brown to the lightest tints 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 skink species: Corucia zebrata is black, and the autosomal dominant color is yellow-green.

Changes in eye color
In all populations, children are most commonly born with unpigmented eyes. However, most babies who have European ancestry have light-colored eyes before the age of one. 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, in theory eye color can be changed. Most eye changes happen when the infant is around one year old, although it can happen up to three years of age. Observing the iris of an infant from the side using only transmitted light with no reflection from the back of the iris, it is possible to detect the presence or absence of low levels of melanin. An iris that appears blue under this method of observation is more likely to remain blue as the infant ages. An iris that appears golden contains some melanin even at this early age and is likely to turn green or brown as the infant ages.

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.

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.

 Light eyes Eyes light and light mixed are 16–12 in Martin scale.  Very light-mixed (blue with gray or green or green with gray) Light-mixed (light or very light-mixed with small admixture of brown pigment)  Mixed eyes Dark eyes 
 * Light: Gray, blue, green. 16–15 in Martin scale.
 * Light-mixed: 14–12 in Martin scale.
 * Mixed: 12–6 in Martin scale. Mixture of light eyes (blue, gray or green) with brown pigment when light and brown pigment are the same level.
 * 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 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. Even though amber is considered to be like gold, some people have russet or copper colored amber eyes which many people mistake for hazel, though hazel tends to be duller and contains green with red/gold flecks, like mentioned above. Amber eyes may also contain amounts of very light gold-ish gray, found in animals like wolves.

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. Many animals such as canines, domestic cats, owls, eagles, pigeons and fish have amber eyes as a common color, whereas in humans this color occurs less frequently.

Blue
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 outer surface of the iris of a blue-eyed person is 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 that lie between the two layers.

Distribution
Blue eyes are most common in the Baltic Sea region, Northern, Eastern and Central Europe, and to a lesser degree in Southern Europe. Blue eyes are also found in parts of the Middle East, most notably in Iran, Afghanistan ([the Indo-Iranian Nuristani people);  as well as in the Levant, especially amongst the Jewish population of Israel. Many modern Israeli Jews are of European Ashkenazi origin, among whom this trait is common (53.7% of Ukrainian Jews have blue eyes ).

A 2009 study suggested that blue eyes were present in Siberia during the Bronze Age; 15 of 25 Andronovo culture specimens (60%) from the Krasnoyarsk area had blue (or green) eyes.

Y-Chromosome DNA testing performed on ancient Scythian skeletons dating to the Bronze and Iron Ages in the Siberian Krasnoyarsk region found that all but one of 11 subjects carried Y-DNA R1a1, with blue or green eye color and light hair common, suggesting mostly European origin of that particular population.

In Estonia, 99% of people have blue eyes, stated Hans Eiberg from the Department of Cellular and Molecular Medicine at the University of Copenhagen. In Denmark 30 years ago, only 8% of the population had brown eyes, though through immigration, today that number is about 11%. In Germany, about 75% have blue eyes.

A 2002 study found that 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 are continuing to become less common among American children, with only one out of every six or 16.6% of the total population, and 22.3% of the white population having blue eyes.

Genetics
In humans, 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). In 2008, new research suggested that people with blue eyes have a single common ancestor. Scientists tracked down a genetic mutation that leads to blue eyes. "Originally, we all had brown eyes," said Eiberg. 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 probably living in the northwestern part of the Black Sea region (around modern Romania) 6,000–10,000 years ago during the Neolithic revolution. 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 are rare in mammals; one example is the quite recently-discovered Blue-eyed Spotted Cuscus (Spilocuscus wilsoni). The trait is hitherto known only from a single primate other than humans – Sclater's Lemur (Eulemur flavifrons) of Madagascar. While some cats and dogs have blue eyes, this is usually due to another mutation which is associated with deafness. But in cats alone, there are three known mutations which produce blue eyes – the one found in Siamese cats does not have adverse health effects, while the others – that of blue-eyed white cats and the Ojos Azules breed – are assiociated with congenital neurological disorders.

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 is most common in East Asia, Southeast Asia, South Asia, West Asia, Oceania, Africa, Americas, etc.

Light or medium-pigmented brown eyes are common in Europe, Iran, Afghanistan, Armenia, Pakistan and Northern India, as well as some parts of the Middle East. Light-pigmented brown eyes are sometimes referred to as "honey eyes".

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 are most common in Northern and Eastern Europe. Gray eyes can also be found in parts of North West Africa (Aurès Mountains) among the Algerian Shawia people and in the Middle East, most notably in Iran, Afghanistan ([the Indo-Iranian Nuristani people), and Pakistan (the Kalasha, another Indo-Iranian people);   Under magnification, gray eyes exhibit small amounts of yellow and brown color in the iris. Ultimately, there are at least two things that 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.

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 other genes. Green eyes were present in south Siberia during the Bronze Age. They are most common in Northern and Central Europe. They can also be found in Southern Europe and North Africa. In Iceland, 89% of women and 87% of men have either blue or green eye color. A study of Icelandic 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's anterior border layer. Hazel eyes often appear to shift in color from a brown to a green. Although hazel mostly consists of brown and green, the dominant color in the eye can either be brown/gold or green. This is how many people mistake hazel eyes to be amber and vice versa. 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. In some hazel eyed individuals, the iris may exhibit some scant blue color within the more prominent brown/gold/green coloring.

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.

Red and violet
The eyes of people with severe forms of albinism may appear red under certain lighting conditions owing to the extremely low quantities of melanin, allowing the blood vessels to show through. In addition, flash photography can sometimes cause a "red-eye effect", in which the very bright light from a flash reflects off the back of the eyeball, which is abundantly vascular, causing the pupil to appear red in the photograph.

Although the deep blue eyes of some people such as Elizabeth Taylor can appear violet at certain times, true violet-colored eyes only occur due to albinism.

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. However, a study in 2000 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. Yellowing of the whites of the eyes in people with darker pigmented skin is often due to melanin 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.

Wilson's disease
Wilson's disease involves a mutation of the gene coding for the enzyme ATPase7B, which prevents copper within the liver from entering the Golgi apparatus in cells. Instead, the copper accumulates in the liver and in other tissues, including the iris of the eye. This results in the formation of Kayser-Fleischer rings, which are dark rings that encircle the periphery of the iris.

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 iris 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 a 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 genetic, such as chimerism, Horners Syndrome and Waardenburg syndrome.

A chimera can have two different colored eyes just like any two siblings can—because each cell has different eye color genes. A mosaic can have two different colored eyes if the DNA difference happens to be in an eye color gene.

There are many other possible reasons for having two different colored eyes. For example, David Bowie has the appearance of different eye colors due to an injury that caused one pupil to be permanently dilated. Another idea about how this can happen is if an early viral infection while in the womb turns an eye color gene on or off in just one eye. Occasionally it can be a sign of a serious disease.

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 pigmentation in one eye. On occasion, the condition of having two different-colored eyes is caused by blood staining the iris after sustaining injury.