Eye color is one of the most visually distinctive human traits, varying widely across individuals and populations.

While once thought to be a simple trait controlled by a single gene, modern genetic research reveals that eye color results from the complex interaction of multiple genes regulating pigment production and distribution in the iris.

Genetic Determinants of Pigmentation

At the core of eye color variation is melanin, the pigment responsible for most coloration in human skin, hair, and eyes. Within the iris, specialized cells called melanocytes produce melanin, which is stored in cellular structures known as melanosomes. The quantity, type, and distribution of melanin within the iris determine its color: high melanin levels lead to brown eyes, intermediate amounts yield green or hazel eyes, and low amounts result in blue eyes.

Genetic control over melanin production involves numerous genes participating in melanogenesis, the biochemical pathway synthesizing melanin from the amino acid tyrosine. Key genes include TYR, which encodes the enzyme tyrosinase critical for melanin synthesis, and TYRP1, regulating pigment type and distribution.

Major Genes Influencing Eye Color

Among the genes implicated in eye color variation, two on chromosome 15—OCA2 and HERC2—are particularly influential. The OCA2 gene encodes the P protein, essential for melanin production and melanosome maturation. Variants in OCA2 influence the amount of pigment synthesized, strongly affecting eye color.

HERC2 contains regulatory elements controlling OCA2 gene expression. A single nucleotide polymorphism (SNP) within HERC2 acts as a switch to modulate OCA2 activity. For example, a specific mutation leads to reduced OCA2 expression, lowering melanin and producing blue eyes. This regulatory relationship explains why small genetic changes can cause significant differences in eye color.

Additional genes such as SLC24A4 and ASIP also modulate melanin levels and contribute to subtle variations between green, hazel, and brown eyes. These genes affect melanosome biology, pigment transport, or the balance between eumelanin (brown-black pigment) and pheomelanin (red-yellow pigment), further diversifying eye color.

Complex Inheritance Patterns Beyond Simple Mendelian Models

Traditional inheritance models once classified brown eyes as dominant over blue eyes, but this simplified view fails to account for observed genetic complexity. Eye color is a polygenic trait, influenced by multiple interacting genes. This interplay results in incomplete dominance, epistasis, and variable expressivity.

Consequently, children with two blue-eyed parents can have green or brown-eyed offspring if they inherit combinations of alleles from other genes increasing melanin production. This phenomenon illuminates the complexity of genetic interactions shaping pigmentation beyond basic dominant-recessive paradigms.

Environmental and Epigenetic Influences

While genes provide the blueprint for eye color, environmental factors and epigenetic modifications can influence pigment expression. For instance, exposure to light over time can darken iris pigmentation.

Epigenetic mechanisms—chemical modifications affecting gene expression without altering DNA—may also modulate melanocyte activity or melanin synthesis. Though these influences are generally subtle, they contribute to the dynamic nature of eye color throughout life.

Health Implications of Genetic Variants in Eye Color

Some genetic mutations affecting pigmentation genes cause disorders such as oculocutaneous albinism, characterized by severely reduced melanin production and very light eye color combined with vision impairments. Additionally, heterochromia, the presence of two different eye colors in the same person, results from mosaic expression or genetic mosaicism in pigmentation genes.

Dr. Rick A. Sturm — board-certified ophthalmologist, "Eye color is complex and is controlled by 16 different genes, not just the single gene that we all previously learned about in high school."

Eye color is shaped by a complex genetic network primarily governing melanogenesis and pigment distribution in the iris. Key genes like OCA2 and HERC2 regulate melanin quantity and type, generating the wide range of colors observed from brown to blue. The polygenic nature of this trait explains inheritance patterns that defy simple Mendelian rules, revealing intricate gene interactions that produce individual variation.