Green eyes are one of the rarest eye colors in humans, only occurring in around 2% of the global population. The genetics behind green eyes have been studied for decades, and research has shown that there are a few key genes involved in producing this eye color. In this article, we will explore the key questions around green eye genetics:
What causes green eyes?
Green eyes are caused by a combination of factors. The main determining gene is the OCA2 gene, also known as the HERC2 gene. This gene codes for a protein involved in the production of melanin, the pigment that gives color to our hair, skin and eyes. The level and type of melanin present determines our eye color.
In green eyes, there is a reduced amount of melanin present compared to brown eyes. The melanin that is present contains more of the yellowish pheomelanin pigment rather than the brown/black eumelanin pigment. This results in an eye color that appears more green or hazel.
How is eye color inherited?
Eye color is a polygenic trait, meaning that multiple genes influence the final eye color. The main gene involved is OCA2, but other modifier genes also have an effect. Since multiple genes are involved, the inheritance of eye color does not follow simple Mendelian inheritance.
In general, brown eye color is considered dominant over green and blue eyes. This means that if one parent has brown eyes and the other has green eyes, the child is more likely to end up with brown eyes. However, the other modifier genes can sometimes result in a child having a different eye color than either parent.
What are the key genes involved in green eye color?
Here are the main genes involved in determining green eye color:
OCA2
The OCA2 gene provides instructions for making the P protein which is involved in melanin production. Specific variations in this gene reduce the amount of melanin pigment made, leading to lighter eye colors like green, hazel and blue.
HERC2
The HERC2 gene regulates the expression of the OCA2 gene through a mechanism involving a transcription factor protein. Certain mutations in HERC2 can switch off OCA2 expression, resulting in reduced melanin production.
SLC24A4
The SLC24A4 gene codes for a protein that transports calcium and potassium ions into melanocytes – the cells that produce melanin. Variants in this gene affect melanin composition and can contribute to green/hazel eye color.
TYR
The TYR gene provides instructions for making the enzyme tyrosinase, which is crucial for melanin production. Mutations in TYR can reduce enzyme activity leading to less melanin pigment in the eyes.
The Main Gene – OCA2
The OCA2 gene plays the most significant role in determining green eye color. Let’s explore the genetics of this key gene in more detail:
What is the OCA2 gene?
The oculocutaneous albinism II (OCA2) gene provides instructions for making the P protein which is involved in melanin production. This gene is located on chromosome 15 and is composed of over 300,000 base pairs of DNA code.
The P protein acts as an ion transporter, moving ions across cell membranes. It helps regulate pH and ion levels within melanocytes, which are crucial for melanin synthesis.
How do variants in OCA2 lead to green eyes?
There are a few key genetic variants in the OCA2 gene that can lead to green eye color:
rs1800401
This variant involves a cytosine (C) to adenine (A) change in the DNA sequence of OCA2. The C allele results in normal melanin production, while the A allele reduces melanin levels.
Individuals with two copies of the A allele (A/A genotype) tend to have lighter eye colors like green/hazel. Those with only one copy (A/C genotype) may also have green/hazel eyes depending on other gene variants.
rs7495174
This single nucleotide polymorphism (SNP) involves a T to C transition. The T allele is associated with decreased melanin production compared to the C allele. People with one or two copies of the T variant are more likely to have green/hazel eyes.
rs6497268
This variant consists of a G to A substitution, with the A allele correlated with lighter eye pigmentation. Having two copies of the A allele is linked to higher chances of green/hazel eye color.
How common are these OCA2 variants?
The allele frequencies of these OCA2 variants differ across populations. Here is a table summarizing the frequencies:
| Variant | Allele | European Frequency | African Frequency | Asian Frequency |
|---|---|---|---|---|
| rs1800401 | A allele | 0.79 | 0.06 | 0.04 |
| rs7495174 | T allele | 0.71 | 0.34 | 0.27 |
| rs6497268 | A allele | 0.65 | 0.21 | 0.18 |
As shown, the variants linked to lighter eye colors like green and hazel are much more common among Europeans compared to other populations. This correlates with the higher prevalence of lighter eye colors in European populations.
Modifier Genes
In addition to OCA2, several other genes influence the final eye color by modifying the amount and type of melanin produced:
HERC2
The HERC2 gene is adjacent to OCA2 on chromosome 15 and regulates its expression. Specific mutations in HERC2 disrupt a transcription factor binding site required for OCA2 activation. When OCA2 is switched off, melanin production is dramatically reduced leading to lighter eye colors.
SLC24A4
Variants in this gene affect the composition of melanin, leading to increased production of pheomelanin which causes green/hazel eyes. The protein encoded by SLC24A4 exchanges calcium and potassium ions in melanocytes, which impacts melanogenesis.
TYR
Mutations in TYR lead to oculocutaneous albinism type 1. Being homozygous for dysfunctional TYR mutations results in complete lack of melanin. Heterozygous carriers may have some TYR activity, allowing for small amounts of melanin and green eye color.
IRF4
This gene regulates pigmentation by interacting with the melanogenesis pathway. Variants linked to less IRF4 expression are associated with lighter eye colors.
MLPH
The protein product of MLPH delivers melanin granules to keratinocytes. Mutations can cause coating defects of melanin granules leading to diluted pigmentation in the eyes.
Population Genetics of Green Eyes
The prevalence of green eyes varies substantially between populations around the world:
Europe
Green eyes are most common in European populations, with frequencies highest in countries like Ireland, Scotland and northern Germany. This correlates with the increased frequency of OCA2/HERC2 variants in Europeans.
| Country | % with Green Eyes |
|---|---|
| Ireland | 86% |
| Scotland | 30% |
| England | 19% |
| Germany | 16% |
| Netherlands | 10% |
| France | 9% |
Americas
In the United States and Canada, green eyes occur in around 2% of the population. They are somewhat more common among those of recent European ancestry:
| Ancestry | % with Green Eyes |
|---|---|
| European | 2.4% |
| Hispanic | 1.7% |
| African | 0.6% |
| Asian | 0.2% |
Africa and Asia
Green eyes are extremely rare among native populations in Africa and Asia. The OCA2/HERC2 alleles linked to green eyes are very uncommon in these regions. Hazel eyes are somewhat more common than pure green.
The Future of Green Eye Genetics
Advances in DNA sequencing and genome editing technologies may shed further light on green eye genetics:
High-Resolution DNA Analysis
Emerging sequencing techniques allow high-precision mapping of genetic variants influencing eye color. This can aid identification of novel alleles in OCA2, HERC2 and other pigmentation genes.
Functional Testing in Cell Lines
Using CRISPR genome editing, specific mutations can be introduced into human melanocyte cell lines in vitro to functionally test their effects on melanin production and eye color.
Gene Therapy
In the distant future, directly manipulating eye color genes through gene therapy injections into the iris may provide a way to shift eye color. However, major hurdles remain both scientifically and ethically.
Risks of Engineering Eye Color
While understanding green eye genetics can be intellectually fascinating, some warn strongly against using this knowledge for cosmetic genetic manipulation. The effects of artificially tinkering with such complex traits are impossible to fully predict.
Conclusion
In summary, green eye color arises from an intricate interplay of genetics and melanin biochemistry. While OCA2 seems to be the master regulator, changes in over a dozen genes influence the final eye shade. Advancing knowledge of these genetic factors may reveal new insights into the biological mechanisms behind this rare and striking eye color. However, many unknowns remain around how different alleles ultimately translate into the palette of human eye phenotypes we see today.
