How genetics is revealing skin colour biology is more than skin-deep

Students of a school in Rameswaram, Tamil Nadu, wave at the camera, April 18, 2018.
| Photo Credit: Church of the King/Unsplash

Skin, with its wide spectrum of textures, hues, and histories, has long captivated the imagination of poets and storytellers. It has served as a canvas for the expression of beauty, identity, and cultural symbols. The diversity of skin colour across human populations is a product of human genetics, the migration of peoples, and the complex interplay between genes and the environment.

Together with its colour, skin opens a window into the underlying human pathophysiology, and not just because it’s the largest organ, and has as a result been the subject of many scientific and medical investigations as well. The natural colour of human skin and changes therein help clinicians diagnose a number of medical conditions. For example, genetic defects can result in the absence of pigmentation by birth, such as albinism; partial or complete depigmentation can also result in disorders like vitiligo. A number of drugs, including antimalarials and chemotherapy agents, also cause skin pigmentation.

But for all of skin’s significance and wonder, its colour has also been the basis of social hierarchies, racism, and other forms of discrimination. Recognising the biological basis of skin and celebrating the diversity of skin colour could instead foster a deeper appreciation of human differences and promote inclusivity.

What is the effect of ultraviolet radiation?

The pigment melanin determines the colour of skin. It is produced by cells called melanocytes. A number of genes and factors influence the type and size of melanin particles as well as its production, transport, and distribution.

Scientists widely believe exposure to ultraviolet light from the Sun has been the dominant driver of skin colour throughout history. Across geographies, colours have also displayed a close connection to the latitude, which in turn is correlated with ultraviolet exposure. There is also consensus that lighter skin colour across higher latitudes is the result of humans adapting to produce vitamin D — again, a process induced by ultraviolet light. Skin pigmentation also protects nutrients like folate from being broken down by ultraviolet radiation.

This said, systematic approaches to understand and document skin colour have been only of recent interest. In 1735, the Swedish biologist Carl Linnaeus classified humans into four ‘varieties’ based on skin colour. The Austrian anthropologist and explorer Felix von Luschan designed a scale with which to compare skin colour in the 19th century. The scale has 36 colours and is used to this day.

Dark-skinned humans evolved from apes around 1.2 million years ago by shedding body hair and adapting to ultraviolet radiation. Skin colour is also one of the more striking phenotypes (attributes produced by genes’ interactions with the environment) in humans, being closely related to their migration and adaptation as they moved out of Africa around 100,000 years ago.

Researchers have found genes associated with the melanocortin 1 receptor, a protein associated with the creation of light skin, in the DNA of Neanderthals from Spain and Italy but not from Croatia, and not in Denisovans.

Which genes are involved in skin colour?

As for modern-day human skin colour: the prevailing hypothesis is that it’s the result of natural selection across a few genes. Two of these, SLC24A5 and SLC45A2, are the most well-studied. They affect skin colour in modern Eurasians. Other genes like MC1R, TYRP1, and OCA2 affect that of East Asians. And all of them show signals of natural selection.

Researchers widely believe Europeans and East Asians adapted to have lighter skin through independent processes. Some evidence has been found for natural selection in Europeans around 11,000-19,000 years ago. A 2015 study led by Harvard Medical School, together with several international organisations, suggested Europeans became mostly light-skinned by at least 4,000-6,000 years ago. Later, the admixture of global populations plus local adaptations resulted in the large diversity of skin colour we observe today.

There are many exceptions to this general rule, however. For example, the Inuit people who have inhabited Alaska for more than five centuries, have darker yellowish brown skin compared to other populations at the same latitude. This has been a puzzling exception for many years. Researchers have hypothesised a high vitamin D intake and high ultraviolet exposure due to longer days have combined to create this anomaly.

How does skin colour vary?

Human genetic conditions like albinism — which results in partial or complete loss of pigment of the skin — provide insights into the biology of skin pigmentation and how society addresses people with rare conditions. Around one in 20,000 individuals around the world are estimated to have this condition, but the prevalence could be 20-times higher among the Tonga people of Africa and 120-times higher among the Guna people of South America. Individuals with albinism are highly predisposed to developing skin cancers, not to mention also having to suffer regressive social attitudes.

The latest advances in genomics are improving our understanding of the biology of skin pigmentation. In a paper published in the journal Nature Genetics in January 2024, researchers at the University of Pennsylvania used genome editing and chromosomal conformational capture to identify the regulators of a number of genes involved in skin pigmentation. They identified the mechanisms by which mutations in the regulatory regions of four genes could affect pigmentation and its variability. They also identified a new gene, CYB561A3, that regulates skin pigmentation. This work expanded the repertoire of genes we know to be involved in the processes driving pigmentation diversity.

By exploring the scientific and genetic underpinnings of skin colour diversity, we gain insights into the biological processes and our shared evolutionary history as well as confront the complexities of social norms, privilege, and prejudice. Embracing diversity prepares us to embrace the rich heritage of humankind and inspires us to strive for more harmonious living.

The authors are senior consultants at the Vishwanath Cancer Care Foundation and adjunct professors at Indian Institute of Technology, Kanpur. All opinions expressed are personal.