A genome-wide genetic screen uncovers determinants of human pigmentation

Abstract

Skin color, one of the most diverse human traits, is determined by the quantity, type, and distribution of melanin. In this study, we leveraged the light-scattering properties of melanin to conduct a genome-wide screen for regulators of melanogenesis. We identified 169 functionally diverse genes that converge on melanosome biogenesis, endosomal transport, and gene regulation, of which 135 represented previously unknown associations with pigmentation. In agreement with their melanin-promoting function, the majority of screen hits were up-regulated in melanocytes from darkly pigmented individuals. We further unraveled functions of KLF6 as a transcription factor that regulates melanosome maturation and pigmentation in vivo, and of the endosomal trafficking protein COMMD3 in modulating melanosomal pH. Our study reveals a plethora of melanin-promoting genes, with broad implications for human variation, cell biology, and medicine.

Skin colour: A window into human phenotypic evolution and environmental adaptation

“…Structural variants (SVs) are also a significant source of genomic variation that involve changes in multiple or even thousands of bases that can have a significant impact on the genome (Alkan et al, 2011). Therefore, SVs may also serve as tion by regulating the pH of melanosomes (Bajpai et al, 2023). This study provides new evidence to improve the genetic map of melanin synthesis, and further analysis of the molecular evolutionary process of these genes will provide more information on the evolution of human skin colour.…”

A single-cell transcriptome atlas of Lueyang black-bone chicken skin

“…Inhibiting MITF transcription results in decreased melanin synthesis ( Yuan et al, 2016 ). TYR is the rate-limiting enzyme and key enzyme for melanin synthesis ( Bajpai et al, 2023 ). Cho et al (2021) conducted molecular analysis of TYR and found that abnormal transcription of TYR leads to the recessive white feather phenotype.…”