Melanin

Throughout antiquity, skin coloration has had a tremendous impact on humanity, causing various health effects along with discrimination and racism of ethnic groups. Melanin is a pigment that has been naturally selected to help humans adapt to different geographical regions and selective pressures. Variations in skin coloration, the amount of melanin in the skin, are related to the amount of ultraviolet (UV) radiation and nutrient synthesis in the body. A common misconception is that differences in skin pigmentation have a biological basis in distinguishing among “races.” Today, we now understand that with a high correlation between latitude and UV levels, most variations in skin coloration are due to differences among geographical regions.

Evolution of Skin Coloration

Many anthropologists believe that the earliest hominids were covered in dark black hair with low or unpigmented underlying skin. Various models have been produced to show human evolution and the adaptations that favor increased levels of melanin in the skin. During the transitional period, it was thought that the need for thermoregulation led to a decrease in body hair and a subsequent increase in sweat glands. Because the brain is heat sensitive, these mechanisms allowed for increased activity in growth. In response to a decrease in hair covering, the body adapted by increasing melanin production in the skin to protect against the harmful UV radiation. Throughout human evolution, skin pigmentation has continuously varied and adapted depending on the selective pressures. As a result, skin pigmentation cannot be used to track or determine evolutionary development of humans today.

Melanin Production

Melanin is a pigment that helps to determine skin, hair, and eye color. It is also found in the medulla, the zona reticularis of the adrenal gland, the inner ear, and the substantia nigra of the brain. The production of melanin depends on the enzyme tyrosinase that converts the amino acid (building block of protein) tyrosine into dopaquinone. The dopaquinone molecule is then transformed into a variety of colored pigments. It is the Golgi organelles of the melanocytes that package melanin into vesicles called melanosomes. These vesicles are then shipped into the cell processes (extensions) of the melanocyte, where the processes are ingested by keratinocytes (cells of the epidermis that produce keratin). Thus, the melanin has been transferred from the melanocytes into the keratinocytes of the epidermis (outermost) layer of the skin.

There are a few different types of melanin in the human body. Eumelanin is the most abundant type and is found in skin and hair. Pheomelanin is less common but is responsible for the reddish tone in red hair and is also found in skin. Lastly, neuromelanin is found in the substantia nigra region of the brain and is a dopamine by-product.

Genetic Polymorphism and Natural Selection

Skin pigmentation is one of the most variable human characteristics; however, little is known about its genetic and evolutionary paths. Skin color is a polygenic trait that is controlled by the interaction of multiple genes on different locations of chromosomes (strands of DNA that carry genetic information). The large variations of skin pigmentation among different populations are most likely due to natural selection. Depending on the geographical region, different selective pressures, such as vitamin D synthesis, nutrient breakdown, and photoprotection from UV radiation, would change the amount of melanin produced in the body. Researchers have found that although decreased melanin levels have increased risk for skin cancer, most cases do not take effect until later in life and seldom cause death; thus, they have less of an influence on reproductive success.

Melanin and UV Radiation

In the skin, melanin functions as a filter for UV radiation by means of absorbing and scattering the electro-magnetic radiation produced by the sun. The amount of protection is dependent on the amount of UV radiation that is able to pass through the earth’s atmosphere (e.g., clouds, ozone, dust particles) to reach the body surface along with the location and density of melanin in the skin. Thus, deeply melanized skin provides protection against UV radiation, which is the primary cause of skin cancer. With ultraviolet-B (UVB) radiation causing sunburns that damage sweat glands, immediate negative effects on thermoregulation occur. Thus, the high density of melanin in darker skin is able to provide enhanced photoprotection along with more efficient recovery from growth inhibitory effects of UVB exposure. In addition, melanin has the free radical ability to absorb any carcinogenic or toxic compounds produced by photochemical reactions.

One of the benefits of UV radiation is its involvement in the synthesis of vitamin D. Because vitamin D is necessary for uptake of calcium and phosphate minerals from the intestines, it is vital for normal bone metabolism and skeletal growth along with nerve and muscle functioning. So long as humans are exposed to sufficient sunlight, UV photons are able to synthesize pre-vitamin D that is subsequently transformed into vitamin D at body temperature. Melanin has the ability to block the absorption of UV light that is needed to make vitamin D. Lighter skinned humans with low to moderate levels of melanin in their skin absorb more UV light; thus, they are able to synthesize more vitamin D. These individuals are at higher risk for developing skin cancer, especially when residing in areas of high UV radiation such as near the equator. On the other hand, there are also people who live in northern regions with low annual UV exposure. These individuals are at risk for having a vitamin D deficiency and must make sure that they compensate by ingesting enough vitamin D in their diets to be absorbed by their intestines. A deficiency of this vitamin may cause bone disorders such as rickets (bowed bones and inflamed joints), osteomalacia (softening of bones), and osteoporosis (reduction in quantity of bone tissue). These may lead to immobilization, bone deformities, or even death.

Another molecule that is affected by UV light is folate. The photosensitivity of the folate molecule leads to complications because it is readily degraded by UV light. Folate is produced in the body from folic acid, an essential nutrient involved in nucleotide (building blocks of DNA and RNA) formation, and has been found to play crucial roles in red blood cell and bone marrow development. Defective and deficient folate levels have been linked to spermatogenesis (production of sperm) and various neural tube defects during embryo development. Thus, to inhibit the breakdown of folate, humans have adapted by increasing melanin formation in the skin to enhance reproductive success.

Within the eye, the color of the iris varies among humans and is dependent on the amount of brown or black pigment and the scattering of light caused by the tissue of the iris. For example, in some forms of albinism, the pupil appears to be red because there is no melanin pigment to absorb light, thereby causing the light to reflect off the blood vessels in the back of the eye. Furthermore, similar to the reason why the sky is blue and not black as in outer space, blue-eyed individuals are due to light scattering off the iris tissue.

Melanin also determines hair color. Near the base of the hair follicle, the bulb matrix contains melanocytes that produce and transfer melanin to keratinocytes in the outer portion of the hair follicle. Depending on the type of melanin and the amount of brown, black, and red pigment, various shades of hair color can be produced.

Skin Coloration

Skin color is determined by a number of factors, including genetic makeup, hormone levels, carotene levels, and amount of sun exposure. Depending on the location of pigments and the amount of sunlight reaching the human skin, absorbed UV light not only darkens melanin pigments but also stimulates melanin production.

In addition, the reddish tone that is often visible when a human blushes or is angry is caused by an increase in blood flow through the skin, whereas a pale color in the skin is evident from decreased blood flow that occurs during a heart attack. Furthermore, cyanosis or decreased oxygen blood levels cause a dark bluish or purplish coloration of the skin.

During pregnancy, melanin production is affected by the hormones estrogen and melanocyte-stimulating hormone (MSH). The MSH is able to darken the skin by binding to receptors on melanocytes to stimulate melanin production. This is the reason for the darkening of the nipples, areolae (bumpy region surrounding the nipple), and genitalia.

Lastly, a yellow pigment called carotene is a good source of vitamin A and can be found in plants such as carrots. Because carotene is a fat-soluble compound, excess amounts accumulate in the epidermis and fat cells, causing the skin to develop a yellowish color.

Diseases and Complications

Some people inherit specific genes that cause them to be unable to produce tyrosinase, a necessary enzyme for melanin production. This condition, known as albinism, causes little or no production of melanin pigment in these people’s eyes, skin, and hair. Aside from risk of isolation and vision problems, so long as sun-protective methods are used, albinos live normal life spans. This is clearly visible when looking at the Hopi Indian tribe. It has been suggested that the extremely high rate of albinism in this tribe, 1 in 200 people, is due to a mating advantage that is favorable and selected for “culturally.”Albinism is a recessive trait that occurs in 1 in 17,000 people in the United States. Other diseases, such as Addison’s, cause increased pigmentation by increasing the secretion of adrenocorti-cotropic hormone and MSH.

Because skin cancer is the most common of all cancers, awareness of skin protection methods has become extremely important. The majority of cases with skin cancer are attributed to UV radiation from the sun. Thus, the people with the highest risk are those who are fair-skinned and live in areas of the world where high amounts of UV radiation penetrate the earth.

The most frequent type of skin cancer is basal cell carcinoma. Fortunately, this type rarely metastasizes (spreads to other areas of the body) and can be cured by radiation or removal. Squamous cell carcinoma is more life threatening because it may metastasize, but it usually remains a localized keratinized tumor (a swelling or growth) in the epidermis. Last, although malignant melanoma is a less common form of skin cancer, it often arises from melanocytes that are within moles and may become life threatening. Although higher melanin skin levels lower the risk of skin cancer, they still occur in all skin colors around the world. The most effective means of preventing sunburn and skin cancer is by limiting sun exposure and using effective sunscreens that block both UVA and UVB radiation.

The fields of medicine and anthropology have made great strides toward uncovering our evolutionary past. Melanin plays a vital role, whether directly or indirectly, in human health, history, and evolution. Depending on the particular geographical region, selective pressures have allowed humans to adapt so as to enhance their reproductive success. With technological improvements, the scientific world will continue to make discoveries to improve our understanding of melanin and its effects on the human body. For example, recent studies have shown correlations between multiple sclerosis and skin pigmentation. Further research will enable our health care system to have a better understanding of factors affecting these diseases that will enable improved preventive measures and more effective treatments. With increased knowledge, dedication, and opportunity, new cures for these diseases and cancers might develop in the near future.

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