New genes that regulate melanin production in humans identified

Melanin, the pigment that imparts color to human skin, is synthesized within specialized structures called melanosomes, which reside within pigment-producing cells known as melanocytes. Although the quantity of melanocytes remains uniform across all individuals, the extent of melanin production varies, giving rise to the diverse range of human skin tones.

In a groundbreaking endeavor, researchers harnessed the power of CRISPR-Cas9 technology to manipulate genes within melanocytes. Their objective was to discern the factors governing disparate melanin levels. Through a systematic process, they systematically deactivated more than 20,000 genes in millions of melanocytes, meticulously observing the resultant impact on melanin synthesis.

To distinguish the melanocytes that exhibited reduced melanin due to gene manipulation from the unaffected cells, an ingenious method was developed. This method, designed by Bajpai, utilized in vitro cell cultures. It relied on a novel technique to gauge and quantify the melanin-producing activity of melanocytes. By subjecting these cells to light, the researchers gauged whether the light was absorbed or scattered by the melanin present.

The scattering of light would be more pronounced in cells abundant with melanin-producing melanosomes, whereas cells with lower melanin content would exhibit minimal scattering. Employing a process known as side-scatter of flow cytometry, the researchers effectively separated cells with distinct melanin levels. Subsequently, these isolated cells were subjected to thorough analysis, revealing the identity of genes that influence melanin production. This method unveiled both previously identified and novel genes pivotal in regulating melanin synthesis in humans.

An astonishing 169 genes with diverse functionalities emerged as contributors to melanin production. Remarkably, 135 of these genes had not been previously associated with pigmentation. Furthermore, the researchers elucidated the roles of two newfound genes: KLF6 and COMMD3. The KLF6 gene, responsible for DNA-binding proteins, was shown to induce a reduction in melanin production in humans and animals, affirming its significance in melanin synthesis across species. Meanwhile, the COMMD3 protein was found to govern melanin synthesis by modulating the acidity levels of melanosomes.

In a historical context, greater pigmentation evolved to shield against the adverse effects of ultraviolet radiation, especially for populations living near the equator or exposed to prolonged sunlight. However, as human populations migrated to regions with reduced sunlight exposure, a diminished requirement for melanin emerged. Consequently, melanosomes produced less melanin, facilitating increased absorption of sunlight.

The implications of this research extend to safeguarding individuals with lighter skin tones from melanoma or skin cancer. By targeting the newfound melanin genes, it becomes conceivable to develop drugs for treating pigmentation disorders like vitiligo.

Additionally, the innovative technological processes pioneered by the research team hold the potential to uncover genes regulating melanin production in other organisms, including fungi and bacteria. Such knowledge could aid in combatting pathogenic microbes, ultimately leading to effective disease interventions.

Dr. Bajpai, a key contributor to this study, undertook his role during his tenure as a professor at the University of Oklahoma. It’s noteworthy that a segment of this research was conducted during his postdoctoral research fellowship at Stanford University.

The culmination of their efforts has been documented in the article titled “A genome-wide genetic screen uncovers determinants of human pigmentation,” published in the esteemed journal Science.

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