The story of our skin – pigmentation genes and global diversity
Pigmentation genes are now one of the fastest-growing areas of research. Just three decades ago, our knowledge of skin colour was very limited – it was believed that only a few single genes were responsible for it.
Meanwhile, over the past 20 years a true revolution has taken place, leading to the discovery of dozens of genetic variants that influence pigmentation. These findings reveal how human migrations, climate, and UV radiation have shaped our skin over thousands of years.
Today, genetic research not only uncovers the history of evolution but also helps us understand health differences between populations and opens the way toward personalized medicine of the future.
The journey that changed skin colour
When the first humans left Africa and began to settle new continents, their bodies faced entirely new challenges. The most important of these was the amount of sunlight – specifically UV radiation. Over thousands of years, it was UV exposure that shaped skin colour, creating an extraordinary palette of shades: from the darkest tones in Africa to the very lightest in Northern Europe.
Let’s recall – why did this matter?
Dark skin protected DNA from excessive UV radiation and reduced the risk of skin cancer. Light skin, on the other hand, enabled the synthesis of vitamin D in conditions of limited sunlight. This balance between protection and the benefits of the sun is one of the most striking examples of evolutionary adaptation.
Skin as a record of genes
The colour of human skin has fascinated scientists for centuries, but only genetics has begun to reveal the mechanisms behind this remarkable diversity. Skin pigmentation is not a matter of chance – it is the result of specific genes that, over thousands of years of evolution, helped our ancestors adapt to their environments.
Genes, the genome, and the great revolution in knowledge
Humans possess around 20,000–25,000 genes, of which about 19,000 code for proteins (Ensembl, NCBI 2024). Back in the 1990s, scientists believed that this number had to be much higher – even over 100,000. The breakthrough came with the Human Genome Project (HGP), completed in 2003. For the first time, the entire human genome was mapped, and the exact number of genes was determined.
Gene vs. genome – what’s the difference?
A gene is a fragment of DNA that contains the instructions for building a specific protein or RNA molecule. The genome, on the other hand, is the entirety of an organism’s genetic material – all the genes together with the non-coding sequences that regulate their activity.
The Human Genome Project showed that what defines humans is not the sheer number of genes, but the interactions between them, the environment, and evolution. Against this backdrop, the group of pigmentation genes stands out as a small portion of our DNA that has had a profound impact on human history.
Although more than 20 years have passed since the HGP, research on pigmentation genes and their influence on health is still in a phase of rapid development. Every year, discoveries emerge – additional gene variants linked to skin colour, as well as their roles in immunity or vitamin D metabolism. Scientists agree: this is only the beginning of understanding the highly complex puzzle in which genes, environment, and lifestyle intertwine to create our unique story written in the skin.
MC1R – the gene of red hair, freckles, and melanoma risk
One of the best-studied genes associated with pigmentation is MC1R (Melanocortin 1 Receptor), often called the “red hair gene.” Mutations in this gene determine whether melanocytes produce more eumelanin (the dark pigment with strong protective effects) or pheomelanin (the lighter pigment, less effective at blocking UV radiation). Individuals carrying MC1R variants are more likely to have fair skin, red hair, and freckles – a phenotype particularly sensitive to UV exposure.
MC1R variants, common in Northern Europe, increase the risk of skin cancers, including melanoma (Garcia-Borron et al., Photochemistry and Photobiology, 2014). This is why people with red hair and very fair skin are considered a high-risk group.
In the future, genetic analysis of MC1R may become part of cancer prevention strategies, helping to identify individuals who require more frequent dermatological screenings or stricter sun protection measures.
SLC24A5 and other genes that “lightened” Europe
A major breakthrough came with a 2005 Science publication, which identified a mutation in the SLC24A5 gene as a key factor in the lightening of European skin. A small change – the substitution of a single amino acid – produced a dramatic phenotypic effect.
- SLC45A2 – the “lightening” gene for skin and hair
The SLC45A2 gene is responsible for transport processes within melanosomes, and its mutations cause a significant reduction in pigmentation – clinically known as oculocutaneous albinism type 4 (OCA4). Beyond albinism, its variants are also associated with differences in skin shade between populations, particularly in Europe. - TYR – the key enzyme in melanin production
Tyrosinase, encoded by the TYR gene, catalyses the reactions that initiate melanin synthesis (converting tyrosine to dopaquinone). Mutations in TYR result in oculocutaneous albinism type 1 (OCA1), characterised by a significant or total lack of pigmentation. - OCA2/HERC2 – how blue eyes emerged
A variant in intron 86 of the HERC2 gene (rs12913832) is the main determinant of blue eyes. It works by suppressing the expression of OCA2. This is the only widely spread genetic factor influencing eye color across human populations.
Ancient DNA studies further reveal that about 7,000 years ago, inhabitants of Europe (for example, the La Braña individual from Spain) had dark skin but light eyes. Light skin only appeared on the continent later, disproving the myth that Europeans have “always” been fair-skinned.
Genes of Africa – the richness of diversity
The diversity of pigmentation genes has its roots in Africa – it was there that nature experimented most boldly:
- MFSD12 – the African foundation of pigmentation
The MFSD12 gene was identified in African populations as one of the most important factors differentiating skin tone (Crawford et al., Science, 2017). Its variants influence the production of eumelanin and pheomelanin, modulating the intensity of pigmentation. Interestingly, some MFSD12 alleles found today in East African populations are linked to lighter skin tones — similar to those seen in Europe and Asia. This demonstrates that pigmentation diversity in Africa is greater than often assumed, and that light skin is not an exclusively European “invention,” but appeared convergently in multiple regions of the world. - DDB1/TMEM138 – genes of UV protection
The DDB1/TMEM138 gene cluster is involved in repairing DNA damaged by UV radiation. Variants of these genes that emerged and spread in Africa are associated with lighter pigmentation, especially in areas with moderate sunlight. This explains why naturally lighter skin tones are found in East African populations — resembling those of Europeans or Asians (Crawford et al., 2017). These genes are a strong example of how the environment — in this case, UV radiation — shapes the evolution of pigmentation. - OCA2 – one gene, many roles
The OCA2 gene is best known for its role in oculocutaneous albinism type 2 (OCA2), but population studies show that it also accounts for more subtle variations in skin and eye color. Mutations in OCA2 explain much of the natural variation in pigmentation within Africa, and some variants are also shared with Eurasian populations. This highlights how human evolutionary history was full of migrations and genetic exchange, making the global “map of pigmentation” impossible to neatly divide by continent. - Albinism is an extreme example
A striking example of disrupted pigmentation is albinism, caused by mutations in genes such as TYR, OCA2, or SLC45A2. People with albinism have little to no melanin, which not only affects appearance but also dramatically increases the risk of skin cancer under strong UV exposure. In Africa, where UV levels are very high, individuals with albinism are among the most vulnerable populations – their average life expectancy is reduced (WHO, 2022). This example clearly shows how genes and the environment interact in determining health outcomes.
Asia and convergent evolution
One of the most fascinating phenomena in human evolution is convergent evolution – a process in which similar traits emerge independently in different populations. This is exactly what happened with light skin. Both Europeans and East Asians evolved lighter pigmentation compared to African populations, but the underlying genetic mechanisms are different.
In European populations, genes such as SLC24A5 and SLC45A2 played a key role, while in East Asians, other genes became more important, including OCA2, KITLG, and DDB1/TMEM138 (Crawford et al., Science, 2017). This shows that evolution can “invent” different solutions leading to the same outcome – in this case, lighter skin, which better adapts the body to limited UV radiation and makes vitamin D synthesis more efficient.
Genetic studies also indicate that lighter pigmentation appeared multiple times independently in human history, making it one of the best-documented examples of convergence in human evolution (Jablonski & Chaplin, PNAS, 2010).
It is a striking reminder that nature can find diverse ways to solve the same challenge – here, how to ensure sufficient vitamin D production in environments with less sunlight.
Polygenicity – how many genes determine skin colour?
Skin colour is not the result of a single “tanning gene.” It is the outcome of an entire network – dozens of genes working together to influence not only the amount and type of melanin but also the size, number, and distribution of melanosomes. Researchers have already identified over 20–30 key genes, and genomic analyses suggest that in different populations, more than 100 regions of DNA may be involved (Liu et al., Molecular Ecology, 2024). This is why Europeans, Africans, and Asians each have different “genetic recipes” for skin colour – even though the end result, lighter or darker pigmentation, may appear similar.
Genes and vitamin D metabolism – toward personalised medicine
Skin pigmentation is also closely linked to vitamin D metabolism. Studies (Rivera-Paredes et al., Scientific Reports, 2024) show that variants in genes such as SLC24A5 or MFSD12 can be associated with lower levels of vitamin D in the body.
This means that two people with a similar phototype may respond very differently to the same dose of supplementation. This is the direction of nutrigenomics – the science of how our genes influence the body’s response to nutrients and supplements. In the future, vitamin D dosage may be tailored not only to age and body weight but also to an individual’s genetic profile.
Conclusion – genes, sunlight, and the future of personalisation
The history of skin colour is not just a story of the past, migrations, and evolution. It is also a dynamic, fast-growing field of science, where new genes and mechanisms are discovered every year. Thanks to genomic research, we now know that pigmentation is a polygenic trait, and the body’s response to sunlight and vitamin D synthesis is shaped by a complex interaction of genes, environment, and lifestyle.
More and more, science is pointing toward personalisation – a future where both UV exposure and vitamin D supplementation can be tailored to individual needs: genotype, skin phototype, and vitamin D metabolism rate. This means that our knowledge of skin and its colour is not a closed chapter, but a fascinating story still unfolding, opening new possibilities for staying healthy in harmony with light.
Sources:
– Ensembl Genome Browser, Human Gene Counts (2024)
– National Centre for Biotechnology Information (NCBI), Human Genome Resources (2024)
– International Human Genome Sequencing Consortium. (2004). Finishing the euchromatic sequence of the human genome. Nature, 431, 931–945.
– Garcia-Borron JC, Abdel-Malek Z, Jiménez-Cervantes C. (2014). MC1R, the cAMP pathway, and the response to solar UV: extending the horizon beyond pigmentation. Photochemistry and Photobiology, 90(1), 10–20.
– Lamason RL, et al. (2005). SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science, 310(5755), 1782–1786.
– Crawford NG, et al. (2017). Loci associated with skin pigmentation identified in African populations. Science, 358(6365), eaan8433.
– World Health Organization (2025). A.25 Sunscreen, broad-spectrum – prevention of skin cancer in people with albinism. WHO Expert Committee on Selection and Use of Essential Medicines.
– Jablonski NG, Chaplin G. (2010). Human skin pigmentation as an adaptation to UV radiation. PNAS, 107(Suppl 2), 8962–8968.
– Liu F, et al. (2024). Skin colour: A window into human phenotypic evolution and environmental adaptation. Molecular Ecology, 33(4), 939–957.
– Rivera-Paredez B, Hidalgo-Bravo A, López P, … Velázquez-Cruz R. (2024). Skin pigmentation–related gene variants influence serum 25(OH)D levels and vitamin D deficiency — evidence from a Mexican population study.