Skin color is one of the most noticeable and distinctive features of human appearance. The shade of our skin is determined by the amount and type of melanin pigments produced by specialized cells in the skin called melanocytes. Melanin pigments play a vital protective role by absorbing harmful ultraviolet radiation from the sun. The two main types of melanin – eumelanin and pheomelanin – also give skin its varied pigmentation across populations. Understanding the biology of skin color sheds light on human evolution and diversity.
Melanocytes
Melanocytes are dendritic (branching) cells located in the basal layer of the epidermis, the outermost layer of the skin. Melanocytes produce melanin within specialized organelles called melanosomes. The melanosomes are then transferred to neighboring skin cells called keratinocytes. Keratinocytes are the most abundant cells in the epidermis and they endow skin with its color and photoprotection capabilities. Humans have about 1,500 melanocytes per square millimeter of skin.
Melanocytes originate from unpigmented precursor cells called melanoblasts that migrate out from the neural crest during embryonic development. Melanoblasts extensively proliferate and migrate throughout the developing skin and hair follicles. Upon reaching their destinations in the skin and hair, the melanoblasts differentiate into mature melanin-producing melanocytes.
Functions of Melanocytes
- Produce melanin pigments within melanosomes
- Transfer melanin to surrounding keratinocytes to color skin and hair
- Protect skin from UV radiation by melanin absorption
- Determine skin color and pigmented patterns
Keratinocytes
Keratinocytes represent over 90% of the cells in the epidermis, the outermost layer of skin. As keratinocytes move from the basal layer of the epidermis towards the surface, they progressively mature and produce more and more keratin proteins. The keratin proteins provide mechanical strength and waterproofing properties to skin, hair, and nails. In the process of maturation, keratinocytes also receive melanin pigments from melanocytes in the basal layer.
Keratinocytes phagocytose (engulf) the melanosome packages released by melanocytes. The melanin pigments are then arranged around the nucleus of the keratinocytes, protecting their DNA from UV radiation. As the keratinocytes reach the skin surface, they eventually die and flake off as part of normal skin turnover. The melanin pigments break down and are washed away with the shed keratinocytes.
Functions of Keratinocytes
- Provide barrier protection for the skin
- Produce keratin proteins for structural support
- Receive and distribute melanin pigments
- Allow melanin to protect nuclei from UV damage
- Shed skin approximately every 4 weeks
Melanin Pigments
There are two main types of melanin produced by melanocytes: the brown-black eumelanin and the red-yellow pheomelanin. Both eumelanin and pheomelanin are formed from the amino acid tyrosine in a series of biochemical reactions.
Eumelanin polymers efficiently absorb photons across the entire UV spectrum, providing more photoprotection. Pheomelanin has a reduced ability to absorb UV radiation and may even contribute to UV-induced damage when present at high levels.
The ratio of eumelanin to pheomelanin produced determines the color of the skin and hair. Higher levels of eumelanin result in brown and black hues, while higher levels of pheomelanin confer yellow and red hues.
Eumelanin
- Brown and black pigment
- Provides efficient photoprotection from UV radiation
- Higher levels produce darker skin and hair
Pheomelanin
- Red and yellow pigment
- Less efficient at UV absorption
- Higher levels produce red hair and freckles
Genetics of Skin Pigmentation
Human skin color is remarkably diverse across global populations. This phenotypic diversity arises largely due to natural selection of genetic variants that control melanin production and distribution. Some of the key genes involved in determining normal skin pigmentation include:
MC1R
The melanocortin 1 receptor (MC1R) gene plays a major role in controlling melanin type. Variants in MC1R result in increased pheomelanin production, leading to pale skin and red hair phenotypes. MC1R variants may have been selected in northern latitude human populations to allow UVB-induced vitamin D synthesis.
OCA2
The oculocutaneous albinism II (OCA2) gene encodes a melanosomal transmembrane protein involved in the most common form of albinism, a disorder of melanin deficiency. Genetic variations reducing OCA2 expression are associated with decreased eumelanin production and hypopigmentation.
SLC24A5
The solute carrier family 24 member 5 (SLC24A5) gene encodes a protein in melanosomes that imports calcium. A variant of SLC24A5 is nearly fixed in European populations and thought to deplete calcium stores needed for eumelanin synthesis. This results in a switch from dark to lighter skin pigmentation.
TYR
The tyrosinase (TYR) gene encodes the rate-limiting enzyme that catalyzes the first step of melanin production from tyrosine. Mutations in TYR result in oculocutaneous albinism type 1, characterized by severe hypopigmentation.
Additionally, melanin distribution patterns also have a strong genetic component mediated by signaling factors like alpha-melanocyte-stimulating hormone that induce melanin synthesis after UV exposure (tanning).
Diseases Associated with Melanocytes
As the cells responsible for melanin synthesis, melanocytes are central to pigmentation disorders and melanoma skin cancer progression.
Vitiligo
Vitiligo is an autoimmune disease characterized by patchy loss of skin color due to destruction of melanocytes. It affects about 1% of people globally. Both genetic and environmental factors contribute to vitiligo susceptibility.
Albinism
Albinism comprises a group of genetic disorders that impair melanin production, resulting in hypopigmented skin, hair, and eyes. Oculocutaneous albinism affects about 1 in 20,000 people worldwide.
Melanoma
Melanoma is a cancer derived from transformed melanocytes containing oncogenic mutations. Melanoma accounts for only 4% of skin cancers but causes the majority of skin cancer deaths due to its metastatic potential.
Role of Melanocytes in Skin Color Evolution
Skin color has undergone adaptive evolution in humans related to geographic ultraviolet radiation levels and vitamin D requirements. Comparisons of indigenous populations provide insights into this process.
| Population | Location | Skin Color |
|---|---|---|
| Khoisan | Southern Africa | Light brown |
| San Bushmen | Namibia, Botswana | Yellowish brown |
| Bantu | Sub-Saharan Africa | Mid to dark brown |
| Nilotic | Eastern Africa | Dark brown |
| North Africans | Algeria, Egypt | Olive to brown |
| Indigenous Australians | Australia | Brown to black |
| Andaman Islanders | Andaman Islands | Dark brown |
| South Asians | India, Pakistan | Brown |
| Northern Europeans | Scandinavia, British Isles | Pale white |
| Southern Europeans | Spain, Italy | Olive white |
Indigenous sub-Saharan Africans have the highest levels of eumelanin-rich dark skin pigmentation due to intense UV exposure near the equator. Northern Europeans have the lightest skin coloration due to positive selection of depigmenting alleles that maximized vitamin D production under lower UVB levels.
Conclusion
In summary, melanocytes and keratinocytes are the two most important cell types that determine skin color through melanin synthesis, transfer, and distribution. The type and quantity of melanins produced by melanocytes, which are under complex genetic control, give rise to diversity of human skin tones. The melanin pigments also provide a selective advantage by protecting against UV radiation in equatorial regions. Further research continues to uncover new genetic loci and adaptive influences that sculpted the palette of human skin pigmentation during our evolutionary journey out of Africa.
