“OCA2 and HERC2 are the two candidate genes- located on chromosome 15, decides different shades of eye colour. The brown eye is commonest while the blue eye is rarest eye colour in the world.”
Genes form proteins and regulate gene expression. Various eye colour genes located on different chromosomes control colour pattern and inheritance of eye colour.
Yes, the eye colouration is regulated by genes!
The eye colour is a unique characteristic of an organism. A molecule named “Melanin” is responsible for various eye colour pattern. And as it is a protein, it is encoded by a gene or genes. But before discussing the present topic let quickly go through some basics.
Genetic material- DNA/RNA is the basis of all life on earth. It stores, transfer and express information, encoded into bases. Structurally, DNA is almost similar in all made up of sugar, phosphate and nitrogenous bases (A, T, G and C).
However, the amount and function vary.
A functional stretch of DNA is known as a gene, genes are located on chromosomes. Every functional or structural protein is formed by genes. Their expression is regulated by it as well. However, the amount of non-functional DNA is higher in a genome. Anyway coming to the point.
Scientists believe that besides making proteins and gene regulation, genes also performs other functions too. For instance, it governs the behaviour pattern as well.
“More than 150 various genes play a role in deciding eye colour.”
Various genes are associated with determining several eye colour shades. The OCA2 and HERC2 are two genes play an important role in deciding the colour but aren’t only, although.
Let’s start with the basic structure of the eye. The pupil- smaller black dot in the middle of the eye is surrounded by the structure called iris. The melanin forms the layer of the iris which helps in passing light from the outer layer.
The melanin is a kind of protein formed with the help of the TYR gene. Located on chromosome 11, the TYR gene forms the tyrosinase enzyme which stimulates melanin production from melanocytes.
The melanocytes are specialised melanin-producing cells, stores the protein in compartments called melanosomes. Numbers of melanocytes are nearly the same in all, however, the amount of melanin and number of melanocytes decides the eye colour.
Thus, in short, the quality and quantity of melanin is the major factor to determine which eye colour shade is formed.
Take a look at the interesting fact!
With the melanin, the fibrous tissues situated in the iris forms the ‘unique pattern’ for a person. The pattern is uncommon for an individual just like our DNA fingerprint or fingerprint of thumb. Iris scanning is now used for personal identification in various fields.
Notably, it isn’t related to eye colour.
Inheritance of eye colour genes:
Genes follow a distinct Mendelian pattern of inheritance. In the case of monogenic inheritance, the pattern in even more clear. Here, in deciding the eye colour, during the entire process, various genes are involved. So a clear inheritance pattern is not observed. Then how the eye colour genes are inherited and what is their inheritance pattern?
Unlike single gene traits, the eye colouration is a polygenic trait- governed by various genes, located on different chromosomes.
In past, it was believed that the eye colour genetics follow Mendelian inheritance pattern. As the brown shade eye is very much common, it was considered as a dominant trait. While the less common shade blue eye was considered as a recessive trait.
But after the discovery of the molecular structure of a gene, the hypothesis is proven wrong.
Besides, OCA2 and HERC2 genes, TYR, TYRP1, ASIP, SLC24A4, SLC24A5, SLC45A2, IRF4 and TPCN2 are involved in eye colouration as well. As it is polygenic, it is now clear that the eye colour genes do not follow any distinct inheritance pattern.
Interestingly, the parent’s eye colour and related genes play a significant role in deciding their child’s iris colour.
Genes for eye colour:
The gene is located on chromosome 15 which encodes a protein known as “P protein.” The P protein is responsible for the pigmentation and production of melanin from melanocytes. It also helps in the transport of molecules across melanosomes.
The exact mechanism and function of P protein are still unknown. The P protein is also known as Melanocyte-specific transporter protein. Mutations in the OCA2 gene can cause serious health issues like Oculocutaneous albinism, melanoma, Prader-Willi syndrome and Angelman syndrome.
We will discuss some of the genetic conditions associated with it later on in this section.
Very nearer to the OCA2 gene on chromosome 15, the HERC2 gene is located. The present gene is directly not involved in deciding the eye colour, instead, it regulates the OCA2 gene expression.
The region known as 86 intron near the HERC2 gene controls OCA2 gene activity in melanocytes. Various dark and light coloured eyeshades are developed by this “on/off switch.”
The HERC2 gene belongs to the family HERC found in E3 ubiquitin-protein ligases. Scientists have less knowledge regarding the gene function in eye colouration.
Both the present gene explained above are considered as candidate genes for various eye colour shades. Various other genes associated with the pathway are explained below.
Tyrosinase enzyme is encoded by the TYR gene located on chromosome 14. The tyrosinase enzyme is located on melanocytes and helps in the synthesis of melanin. In the beginning, it converts amino acid tyrosine into dopaquinone to melanin.
Apart from the iris, it is also present in skin, hair follicles and retina. Mutation in TRY gene can cause genetic disorders like Oculocutaneous albinism and Melanoma.
The TYRP1 gene located on chromosome 9 forms a protein called tyrosinase-related protein 1. Although the clear function of the enzyme is unknown, yet it is believed that the protein located within melanocytes stabilizes the tyrosinase enzyme.
SLC24A4, SLC45A2 and SLC24A5:
The genes encode various proteins of the family potassium-dependent sodium/calcium exchanger protein. The proteins are involved in the pigmentation process.
The two-pore segment channel 2 gene encodes putative cation-selective ion channel protein. It is located on chromosome 11. Mutation in the present gene can possibly cause melanoma.
The Agouti Signalling Protein gene encodes a paracrine signalling protein, located on chromosome 20. A type of signalling molecule induces the production of pheomelanin- yellow pigmentation in melanocytes. The clear function of the ASIP gene in deciding the eye colour is still unknown.
Interferon regulatory factor 4 gene constructs transcriptional factor interferon regulatory factors. The gene is located on chromosome 6 and is involved in a defence system. It protects our body from pathogenic attack.
The specific function of the IRF4 gene in eye colouration is still not clear yet it is believed that it helps in tryptophan synthesis pathway. It is involved in pigmentation too, especially blue eye colouration.
Genetics of eye colour:
As we said above, the eye colour genes are polygenetic, various genes are involved in various pathways of colouration. Thus it does not follow any distinct pattern of inheritance. OCA2 and HERC2 are the two most common while TRY and TRYA2 are two least common genes linked to eye colour development.
Both the genes are located on chromosome 15 nearer to each other. One of the amino acid tyrosine of the melanin is synthesised by the tyrosine kinase (encoded by TYR). The product is transported by the product of the OCA2 gene- P protein to the melanin.
Interestingly, the HERC2 gene regulated the gene expression of OCA2 by the intronic sequence located near it. The DNA sequences (which do not encode any protein) functions as a promoter to the OCA2 gene.
Read more on gene regulation: DNA To Protein- A Brief Overview Of Gene Expression
Various gene mutations within the HERC2 or OCA2 gene causes severe genetic defects such as Oculocutaneous albinism and melanoma.
Besides OCA2, TYR and TYRP1 are two candidate gene indulge in a present genetic condition. A pigmentation abnormality Oculocutaneous albinism is of various types. However, it follows autosomal recessive inheritance pattern.
A group of condition the OA is associated with abnormal pigmentation of hair, skin and eye. Individuals with this genetic condition look very fair.
Their skin is sensitive to long term sun exposure, sometime, it may results in skin cancer as well.
An individual with the present genetic condition has a vision problem, involuntary eye movements and other problems related to the eye. It occurs 1 in 20,000 people worldwide.
Two recessive autosomal alleles are required to cause it, however, an individual with a single mutant copy remains normal.
Melanoma is a kind of skin cancer begins with melanocytes. Prolonged exposure to the sun causes melanoma.
Various genes are involved in it however, not only genetic factors but the environmental interaction also play an important role in developing tumours in various bodily parts.
Melanoma tumours also form in eyes as well. UV light is the major causative agent of it.
In the majority of cases, the genetic factor follows an autosomal dominant pattern of inheritance.
Some eye colour facts:
- A person may have two different eye colour, those are known as heterochromia.
- Brown eye colour is most common in the world.
- Most babies born with blue eye shade! However, as Melanie level varies with age, their eye colour changes.
- All eye colour shades are originally evolved from the brown eye colour, scientists assume.
- Only 5% of the world’s population has hazel or amber eyeshade. Contrary, brown and blue eye colour is present in 79% and 10% of the world’s population, respectively.
Scientifically it is proved that the brown eye colour is predominantly observed in our ancestors as well. Thus we can say the brown colour allele has ancestry roots.
Notably, due to the adverse environment, some mutations happen in the candidate gene governing brown eye. A new allele of the blue eye was originated.
Various eye colour shades are originated from the interaction between these two alleles.
You have noticed various eye colours like brown, hazel, green, blue, grey and red. Among these, the brown eye colour is most common while the blue or green eyeshades are most rare.
The genetic basis of eye colouration is not defined well till date. Still, it is regulated by genetic factors. The role of OCA2 and HERC2 genes is distinct and well studied.
Conclusively, we can say that the amount of melanin, various alleles of OCA2 and activity of the HERC2 gene collectively decides the shade of eye.
“A person with green or blue eyes are lucky” is just a myth. Eye colour does not determine one’s fate, it’s just a gene variation.
White, D., Rabago-Smith, M. Genotype-phenotype associations and human eye color. J Hum Genet 56, 5–7 (2011). https://doi.org/10.1038/jhg.2010.126