Shades of complexity: New perspectives on the evolution and genetic architecture of human skin

Abstract

Like many highly variable human traits, more than a dozen genes are known to contribute to the full range of skin color. However, the historical bias in favor of genetic studies in European and European‐derived populations has blinded us to the magnitude of pigmentation's complexity. As deliberate efforts are being made to better characterize diverse global populations and new sequencing technologies, better measurement tools, functional assessments, predictive modeling, and ancient DNA analyses become more widely accessible, we are beginning to appreciate how limited our understanding of the genetic bases of human skin color have been. Novel variants in genes not previously linked to pigmentation have been identified and evidence is mounting that there are hundreds more variants yet to be found. Even for genes that have been exhaustively characterized in European populations like MC1R, OCA2, and SLC24A5, research in previously understudied groups is leading to a new appreciation of the degree to which genetic diversity, epistatic interactions, pleiotropy, admixture, global and local adaptation, and cultural practices operate in population‐specific ways to shape the genetic architecture of skin color. Furthermore, we are coming to terms with how factors like tanning response and barrier function may also have influenced selection on skin throughout human history. By examining how our knowledge of pigmentation genetics has shifted in the last decade, we can better appreciate how far we have come in understanding human diversity and the still long road ahead for understanding many complex human traits.

Nutrigenomics of Vitamin D

“…More than 30 genes are known to influence the pigmentation of melanocytes, but single nucleotide polymorphisms (SNPs) affecting the genes KITLG (encoding for a ligand of the receptor tyrosine kinase KIT), TYRP1 (a tyrosine converting enzyme), SLC24A5 , and SLC45A2 (both are ion transporters) had the main impact on skin lightening during the past 10–30,000 years [21,22]. Interestingly, Neanderthals and modern Europeans and Asians evolved light skin independently from each other.…”

Prediction of skin color, tanning and freckling from DNA in Polish population: linear regression, random forest and neural network approaches

“…Several candidate gene loci have been identified to be presumably associated with skin pigmentation traits in people of European ancestry as well as to differ among geographical populations. Only recently, a profound and much broader discussion on the genetic background of human pigmentation diversity has emerged (Quillen et al 2019 ).…”

Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer

“…Since there is evidence that pigmentation genes, such as MC1R and ASIP, have been shaped by natural selection [29,30], polymorphic variants in them may act, in part, by affecting how they are epigenetically regulated to optimize a response to an environment with reduced sunlight.…”