Grey eyes are a rare and intriguing eye color, resulting from low levels of melanin in the iris. The genetics behind grey eyes are complex, involving multiple genes that control melanin production and distribution. While no single “grey eye gene” has been identified, certain genetic factors are known to increase the likelihood of having grey eyes.
The Basics of Eye Color
Eye color is determined by the amount and type of melanin pigment in the iris. Melanin comes in two forms:
– Eumelanin – Brown/black melanin
– Pheomelanin – Red/yellow melanin
People with brown or black eyes have a lot of eumelanin in their irises, while people with blue eyes have very little melanin of any kind. Green and hazel eyes fall in between, with moderate amounts of both eumelanin and pheomelanin.
Grey eyes have only small amounts of melanin in the iris, causing the light to scatter and produce a greyish appearance. But what controls melanin production and distribution in the first place? The key lies in our genes.
Genetic Factors for Grey Eyes
At least 16 different genes influence eye color, affecting the amount and ratio of eumelanin and pheomelanin produced. The key genes involved in grey eyes appear to be:
HERC2 – This gene regulates OCA2 and determines the overall amount of melanin produced. Certain mutations of HERC2 are associated with lighter eye colors.
OCA2 – The P gene. Controls melanin production and distribution. Altered versions reduce melanin levels and increase the likelihood of grey eyes.
SLC24A4 – regulates calcium ions that affect melanin synthesis. Variants of this gene linked to low melanin and light eye colors.
SLC45A2 – The MATP gene. Helps regulate OCA2. Certain mutations cause low melanin levels.
TYR – Controls conversion of tyrosine into melanin. Mutations linked to reduced pigmentation.
These 5 key genes work together to regulate melanin production in the iris. Mutations in one or more of these genes can disrupt melanin synthesis, reducing overall levels and resulting in grey eyes.
The HERC2 Gene
The HERC2 gene on chromosome 15 has a strong association with grey eyes. This gene helps control the expression of OCA2, regulating melanin production.
A specific mutation in HERC2 known as rs12913832 substantially reduces its expression, which in turn lowers OCA2 activity. This leads to a sharp decrease in melanin synthesis in the iris, increasing the chances of having grey eyes.
Research shows that almost all people (98-99%) with grey eyes have this HERC2 mutation, compared to only around 10% of the general population. Having two copies of the mutated HERC2 allele makes grey eyes much more likely.
The OCA2 Gene
The OCA2 gene on chromosome 15 encodes the P protein, which is critical for eumelanin synthesis and melanosome maturation. Disrupting OCA2 can significantly reduce brown/black melanin levels.
Certain mutations in OCA2, such as rs1800407, have been associated with grey, hazel, and blue eye colors. These mutations hinder the P protein’s structure and function, limiting melanin production.
Like HERC2, having two copies of mutated OCA2 alleles greatly increases the chances of having light eyes. In fact, nearly everyone with grey eyes has at least one copy of the rs1800407 variant.
Other Genes Involved
While HERC2 and OCA2 play the biggest roles, other genes also influence melanin levels and distribution:
– The SLC24A4 gene helps regulate melanogenesis by controlling calcium ion concentrations in melanocytes. Certain variants reduce calcium levels, inhibiting melanin production.
– The SLC45A2 gene regulates OCA2 activity and melanin metabolism. Mutations can impair melanin synthesis, decreasing brown/black pigmentation.
– The TYR gene is critical for converting tyrosine into melanin. Disrupted TYR function reduces pigment synthesis.
Together with HERC2 and OCA2, variants of these genes combine to lower overall melanin production and increase the chances of grey eyes. Most people with grey eyes have mutations in several of these genes.
Polygenic Inheritance
Grey eyes are polygenic, meaning multiple genes work together to produce the phenotype. As a result, the inheritance patterns are complex and less predictable than for single-gene traits.
In general, having more mutated grey eye alleles from both parents increases the likelihood of having grey eyes. However, it’s also possible to inherit several variants but still not develop grey eyes due to other genetic and environmental factors.
This polygenic mode of inheritance helps explain why parents with blue eyes can have children with grey eyes, and vice versa. There are many possible allele combinations that can result in low melanin and light eye colors.
Prevalence of Grey Eyes
Only around 1-2% of the global population has grey eyes. They are most common in Northern and Eastern Europeans, especially in countries like Finland and the Baltic states, where up to 10-30% of people have grey eyes.
In the U.S., grey eyes are encontered more frequently among Whites of Northern European ancestry and are particularly concentrated in the Northeast and Great Lakes regions. Still, they remain very rare overall, occurring in less than 5% of American Whites.
Worldwide, grey eyes are substantially less common than blue eyes (8-10% globally) and green eyes (2% globally). However, they stand out for their uniquely light and muted coloration.
Other Factors Affecting Eye Color
Although genetics play the dominant role in determining melanin levels, other factors can also influence eye color:
– Thickness of the stroma – The stroma is the collagen-rich tissue beneath the iris that affects how light scatters. A thicker stroma makes eyes appear lighter.
– Iris pigmentation patterns – Melanin is not distributed uniformly across the iris, which affects the overall color.
– Eye layers – More transparent outer layers cause eyes to appear lighter.
– Environmental factors – Trauma, medications, and sun exposure may slightly alter melanin production.
These secondary factors can cause genetically blue/grey eyes to appear slightly darker or lighter. But genetics remain the primary determinant controlling melanin levels and distribution.
Conclusion
Grey eyes arise from low levels of melanin in the iris stroma caused by genetic variations affecting pigment production and distribution. The main genes involved are HERC2, OCA2, SLC24A4, SLC45A2, and TYR.
Mutations in these genes combine to reduce overall melanogenesis and alter melanin ratios, increasing the odds of grey eyes. While the inheritance patterns are complex, grey eyes typically require inheriting several low-melanin alleles from both parents. They represent a striking example of polygenic inheritance in humans.
| Gene | Function | Grey Eye Mutations |
|---|---|---|
| HERC2 | Regulates OCA2 expression | rs12913832 |
| OCA2 | Controls melanin production | rs1800407 |
| SLC24A4 | Regulates calcium for melanin synthesis | Multiple variants |
| SLC45A2 | Regulates OCA2 activity | Multiple variants |
| TYR | Converts tyrosine into melanin | Multiple variants |