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Skin color diversity is the most variable and noticeable phenotypic trait in humans resulting from constitutive pigmentation variability. This paper will review the characterization of skin pigmentation diversity with a focus on the most recent data on the genetic basis of skin pigmentation, and the various methodologies for skin color assessment. Then, melanocyte activity and amount, type and distribution of melanins, which are the main drivers for skin pigmentation, are described. Paracrine regulators of melanocyte microenvironment are also discussed. Skin response to sun exposure is also highly dependent on color diversity. Thus, sensitivity to solar wavelengths is examined in terms of acute effects such as sunburn/erythema or induced-pigmentation but also long-term consequences such as skin cancers, photoageing and pigmentary disorders. More pronounced sun-sensitivity in lighter or darker skin types depending on the detrimental effects and involved wavelengths is reviewed.

Skin pigmentation is a classic example of a polygenic trait that has experienced directional selection in humans. Genome-wide association studies have identified well over a hundred pigmentation-associated loci, and genomic scans in present-day and ancient populations have identified selective sweeps for a small number of light pigmentation-associated alleles in Europeans. It is unclear whether selection has operated on all of the genetic variation associated with skin pigmentation as opposed to just a small number of large-effect variants. Here, we address this question using ancient DNA from 1,158 individuals from West Eurasia covering a period of 40,000 y combined with genome-wide association summary statistics from the UK Biobank. We find a robust signal of directional selection in ancient West Eurasians on 170 skin pigmentation-associated variants ascertained in the UK Biobank. However, we also show that this signal is driven by a limited number of large-effect variants. Consistent with this observation, we find that a polygenic selection test in present-day populations fails to detect selection with the full set of variants. Our data allow us to disentangle the effects of admixture and selection. Most notably, a large-effect variant at SLC24A5 was introduced to Western Europe by migrations of Neolithic farming populations but continued to be under selection post-admixture. This study shows that the response to selection for light skin pigmentation in West Eurasia was driven by a relatively small proportion of the variants that are associated with present-day phenotypic variation.

Direct sun exposure is one of the most aggressive factors for human skin. Sun radiation contains a range of the electromagnetic spectrum including UV light. In addition to the stratospheric ozone layer filtering the most harmful UVC, human skin contains a photoprotective pigment called melanin to protect from UVB, UVA, and blue visible light. This pigment is a redox UV-absorbing agent and functions as a shield to prevent direct UV action on the DNA of epidermal cells. In addition, melanin indirectly scavenges reactive oxygenated species (ROS) formed during the UV-inducing oxidative stress on the skin. The amounts of melanin in the skin depend on the phototype. In most phenotypes, endogenous melanin is not enough for full protection, especially in the summertime. Thus, photoprotective molecules should be added to commercial sunscreens. These molecules should show UV-absorbing capacity to complement the intrinsic photoprotection of the cutaneous natural pigment. This review deals with (a) the use of exogenous melanin or melanin-related compounds to mimic endogenous melanin and (b) the use of a number of natural compounds from plants and marine organisms that can act as UV filters and ROS scavengers. These agents have antioxidant properties, but this feature usually is associated to skin-lightening action. In contrast, good photoprotectors would be able to enhance natural cutaneous pigmentation. This review examines flavonoids, one of the main groups of these agents, as well as new promising compounds with other chemical structures recently obtained from marine organisms.

Acne vulgaris is a common inflammatory disease. Among patients with darker skin phototypes (Fitzpatrick III–VI), the inflammatory processes of acne stimulate excess melanogenesis and abnormal melanin deposition, leading to pigmentary sequelae known as post-inflammatory hyperpigmentation and post-inflammatory erythema in all skin tones, although post-inflammatory hyperpigmentation is more common in darker skin and post-inflammatory erythema in lighter skin. These pigmentary alterations can be long lasting and are often more distressing to patients than the active acne lesions. This article discusses what is known about acne-related pigmentation, much of which is extrapolated from general study of nonspecific pigment deposition. Because dyspigmentation poses both a significant clinical concern to patients and a therapeutic challenge to clinicians, we formed a working group consisting of pigmentary experts with the aim of increasing awareness and education of acne-related pigmentary sequelae.

Many chameleons, and panther chameleons in particular, have the remarkable ability to exhibit complex and rapid colour changes during social interactions such as male contests or courtship. It is generally interpreted that these changes are due to dispersion/aggregation of pigment-containing organelles within dermal chromatophores. Here, combining microscopy, photometric videography and photonic band-gap modelling, we show that chameleons shift colour through active tuning of a lattice of guanine nanocrystals within a superficial thick layer of dermal iridophores. In addition, we show that a deeper population of iridophores with larger crystals reflects a substantial proportion of sunlight especially in the near-infrared range. The organization of iridophores into two superposed layers constitutes an evolutionary novelty for chameleons, which allows some species to combine efficient camouflage with spectacular display, while potentially providing passive thermal protection. Colour change in many vertebrates originates from pigment dispersion or aggregation. Here, Teyssier et al . show that chameleons rapidly shift colour through a physical mechanism involving a lattice of nanocrystals in dermal iridophores, a second and deeper iridophore layer strongly reflects near-infrared light.

The production of melanin pigments by melanocytes and their quantity, quality, and distribution play a decisive role in determining human skin, eye, and hair color, and protect the skin from adverse effects of ultraviolet radiation (UVR) and oxidative stress from various environmental pollutants. Melanocytes reside in the basal layer of the interfollicular epidermis and are compensated by melanocyte stem cells in the follicular bulge area. Various stimuli such as eczema, microbial infection, ultraviolet light exposure, mechanical injury, and aging provoke skin inflammation. These acute or chronic inflammatory responses cause inflammatory cytokine production from epidermal keratinocytes as well as dermal fibroblasts and other cells, which in turn stimulate melanocytes, often resulting in skin pigmentation. It is confirmed by some recent studies that several interleukins (ILs) and other inflammatory mediators modulate the proliferation and differentiation of human epidermal melanocytes and also promote or inhibit expression of melanogenesis-related gene expression directly or indirectly, thereby participating in regulation of skin pigmentation. Understanding of mechanisms of skin pigmentation due to inflammation helps to elucidate the relationship between inflammation and skin pigmentation regulation and can guide development of new therapeutic pathways for treating pigmented dermatosis. This review covers the mechanistic aspects of skin pigmentation caused by inflammation.

An antitumour tan? Fair-skinned individuals suffer an increased risk of skin cancer and often have a weak tanning response. D'Orazio et al . have developed a genetically defined mouse model of skin 'fairness' based on the Mc1r gene (for melanocortin 1 receptor), which is implicated in fair-skinned humans. UV-induced pigmentation (tanning) in these mice was found to involve keratinocyte expression of melanocyte stimulating hormone. 'Sunless tanning' induced by topical application of a small molecule that mimics this enhanced melanocortin 1 receptor signalling can stimulate pigmentation and thereby protect mice with light skin from DNA damage and cancer formation. A small molecule that mimics enhanced melanocortin 1 receptor signalling in response to ultraviolet light can stimulate pigmentation and thereby protect mice with light skin from DNA damage and cancer formation. Ultraviolet-light (UV)-induced tanning is defective in numerous ‘fair-skinned’ individuals, many of whom contain functional disruption of the melanocortin 1 receptor (MC1R) 1 , 2 , 3 . Although this suggested a critical role for the MC1R ligand melanocyte stimulating hormone (MSH) in this response, a genetically controlled system has been lacking in which to determine the precise role of MSH–MC1R. Here we show that ultraviolet light potently induces expression of MSH in keratinocytes, but fails to stimulate pigmentation in the absence of functional MC1R in red/blonde-haired Mc1r e/e mice. However, pigmentation could be rescued by topical application of the cyclic AMP agonist forskolin, without the need for ultraviolet light, demonstrating that the pigmentation machinery is available despite the absence of functional MC1R. This chemically induced pigmentation was protective against ultraviolet-light-induced cutaneous DNA damage and tumorigenesis when tested in the cancer-prone, xeroderma-pigmentosum-complementation-group-C-deficient genetic background. These data emphasize the essential role of intercellular MSH signalling in the tanning response, and suggest a clinical strategy for topical small-molecule manipulation of pigmentation.

Skin color varies among human populations and is thought to be under selection, with light skin maximizing vitamin D production at higher latitudes and dark skin providing UV protection in equatorial zones. To identify the genes that give rise to the palette of human skin tones, Crawford et al. applied genome-wide analyses across diverse African populations (see the Perspective by Tang and Barsh). Genetic variants were identified with likely function in skin phenotypes. Comparison to model organisms verified a conserved function of MFSD12 in pigmentation. A global genetic panel was used to trace how alleles associated with skin color likely moved across the globe as humans migrated, both within and out of Africa. Science , this issue p. eaan8433 ; see also p. 867 Genome-wide analysis of 2000 Africans identifies and functionally characterizes pigmentation loci. Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5 , MFSD12 , DDB1 , TMEM138 , OCA2 , and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in South Asian and Australo-Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of ultraviolet response genes under selection in Eurasians.

Many cephalopods escape detection using camouflage 1 . This behaviour relies on a visual assessment of the surroundings, on an interpretation of visual-texture statistics 2 – 4 and on matching these statistics using millions of skin chromatophores that are controlled by motoneurons located in the brain 5 – 7 . Analysis of cuttlefish images proposed that camouflage patterns are low dimensional and categorizable into three pattern classes, built from a small repertoire of components 8 – 11 . Behavioural experiments also indicated that, although camouflage requires vision, its execution does not require feedback 5 , 12 , 13 , suggesting that motion within skin-pattern space is stereotyped and lacks the possibility of correction. Here, using quantitative methods 14 , we studied camouflage in the cuttlefish Sepia officinalis as behavioural motion towards background matching in skin-pattern space. An analysis of hundreds of thousands of images over natural and artificial backgrounds revealed that the space of skin patterns is high-dimensional and that pattern matching is not stereotyped—each search meanders through skin-pattern space, decelerating and accelerating repeatedly before stabilizing. Chromatophores could be grouped into pattern components on the basis of their covariation during camouflaging. These components varied in shapes and sizes, and overlay one another. However, their identities varied even across transitions between identical skin-pattern pairs, indicating flexibility of implementation and absence of stereotypy. Components could also be differentiated by their sensitivity to spatial frequency. Finally, we compared camouflage to blanching, a skin-lightening reaction to threatening stimuli. Pattern motion during blanching was direct and fast, consistent with open-loop motion in low-dimensional pattern space, in contrast to that observed during camouflage. The cuttlefish Sepia officinalis uses high-dimensional skin patterns for camouflage, and the pattern matching process is not stereotyped—each search meanders through skin-pattern space, decelerating and accelerating repeatedly before stabilizing.

Skin pigmentation is a complex, conspicuous, highly variable human trait that exhibits a remarkable correlation with latitude. The evolutionary history and genetic basis of skin color variation has been the subject of intense research in the last years. This article reviews the major hypotheses explaining skin color diversity and explores the implications of recent findings about the genes associated with skin pigmentation for understanding the evolutionary forces that have shaped the current patterns of skin color variation. A major aspect of these findings is that the genetic basis of skin color is less simple than previously thought and that geographic variation in skin pigmentation was influenced by the concerted action of different types of natural selection, rather than just by selective sweeps in a few key genes.