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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.

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.

Melanized fungi are known for their remarkable resilience to environmental stress, largely attributed to the protective properties of melanin. In this study, we establish the black yeast Exophiala viscosa as a non-pathogenic, genetically tractable model for the scalable production and functional analysis of DHN-melanin (allomelanin). Cultivation in flasks and bioreactors yielded up to 8.6 g/L of melanin, with the majority tightly incorporated into the cell wall as “melanin ghosts”. Chemical analyses including FTIR, XPS, ssNMR, and EPR confirmed the identity of the pigment as allomelanin and revealed a structural association with chitin. Gene deletions of Pks1, Arp2, and Abr2 validated the DHN-melanin biosynthetic pathway and enabled the generation of pigment-deficient mutants. Functional assays demonstrated that melanin contributes significantly to UV and cold tolerance, while offering limited protection against γ-radiation, suggesting that other pigments,such as carotenoids, may also play a protective role. The unique redox properties, structural integrity, and scalability of melanin production in E. viscosa highlight its potential for bio-derived materials used in radiation shielding, environmental remediation, and thermal regulation. This work establishes E. viscosa as a promising chassis for melanin biomanufacturing and a valuable model for studying fungal melanins in the context of materials science and environmental resilience. Key points • Cultivation of E. viscosa in rich medium yielded up to 8.6 g/L of melanin. • Chemical and genetic analyses identified the pigment as allomelanin. • Melanin enhanced the tolerance of fungal cells to UV radiation and low temperatures.

Butterfly wing patterns are a model system for studying the evolution and development of adaptive traits. Zhang et al. combine RNA-seq and CRISPR/Cas9... Despite the variety, prominence, and adaptive significance of butterfly wing patterns, surprisingly little is known about the genetic basis of wing color diversity. Even though there is intense interest in wing pattern evolution and development, the technical challenge of genetically manipulating butterflies has slowed efforts to functionally characterize color pattern development genes. To identify candidate wing pigmentation genes, we used RNA sequencing to characterize transcription across multiple stages of butterfly wing development, and between different color pattern elements, in the painted lady butterfly Vanessa cardui. This allowed us to pinpoint genes specifically associated with red and black pigment patterns. To test the functions of a subset of genes associated with presumptive melanin pigmentation, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in four different butterfly genera. pale, Ddc, and yellow knockouts displayed reduction of melanin pigmentation, consistent with previous findings in other insects. Interestingly, however, yellow-d, ebony, and black knockouts revealed that these genes have localized effects on tuning the color of red, brown, and ochre pattern elements. These results point to previously undescribed mechanisms for modulating the color of specific wing pattern elements in butterflies, and provide an expanded portrait of the insect melanin pathway.

As a main part of pigmentation disorders, skin depigmentation diseases such as vitiligo and achromic naevus are very common and get more attention now. The pathogenesis of depigmentation includes melanocyte dysfunction and loss, which are possibly caused by heredity, autoimmunity and oxidative stress. Among them, oxidative stress plays a key role; however, few clinical treatments can deal with oxidative stress. As reported, Cistanche deserticola polysaccharide (CDP) is an effective antioxidant; based on that, we evaluated its role in melanocyte and further revealed the mechanisms. In this study, we found that CDP could promote melanogenesis in human epidermal melanocytes (HEMs) and mouse melanoma B16F10 cells, it also induced pigmentation in zebrafish. Furthermore, CDP could activate mitogen‐activated protein kinase (MAPK) signal pathway, then up‐regulated the expression of microphthalmia‐associated transcription factor (MITF) and downstream genes TYR, TRP1, TRP2 and RAB27A. Otherwise, we found that CDP could attenuate H2O2‐induced cytotoxicity and apoptosis in melanocytes. Further evidence revealed that CDP could enhance NRF2/HO‐1 antioxidant pathway and scavenge intracellular ROS. In summary, CDP can promote melanogenesis and prevent melanocytes from oxidative stress injury, suggesting that CDP helps maintain the normal status of melanocytes. Thus, CDP may be a novel drug for the treatment of depigmentation diseases. Cistanche deserticola polysaccharide (CDP) promotes melanogenesis in human epidermal melanocytes via activating mitogen‐activated protein kinase (MAPK) signal pathway, then up‐regulates the expression of MITF, TYR, TRP1, TRP2, and RAB27A. Otherwise, CDP can attenuate H2O2‐induced oxidative stress in melanocytes via enhancing NRF2/HO‐1 antioxidant pathway and scavenge intracellular ROS.

Behavioral impulsivity is common in various psychiatric and metabolic disorders. Here we identify a hypothalamus to telencephalon neural pathway for regulating impulsivity involving communication from melanin-concentrating hormone (MCH)-expressing lateral hypothalamic neurons to the ventral hippocampus subregion (vHP). Results show that both site-specific upregulation (pharmacological or chemogenetic) and chronic downregulation (RNA interference) of MCH communication to the vHP increases impulsive responding in rats, indicating that perturbing this system in either direction elevates impulsivity. Furthermore, these effects are not secondary to either impaired timing accuracy, altered activity, or increased food motivation, consistent with a specific role for vHP MCH signaling in the regulation of impulse control. Results from additional functional connectivity and neural pathway tracing analyses implicate the nucleus accumbens as a putative downstream target of vHP MCH1 receptor-expressing neurons. Collectively, these data reveal a specific neural circuit that regulates impulsivity and provide evidence of a novel function for MCH on behavior. Impulsive behaviour is common in various neuropsychiatric disorders. Here, the authors identify a pathway from the lateral hypothalamus to the ventral hippocampus and the role of melanin-concentrating hormone signaling in these neurons in specifically regulating impulsivity.

Background Blackness and growth traits are regarded as crucial economic traits in black-bone chicken production. In order to meet consumers’ demand for black-bone chickens, it is necessary to study the mechanisms of body weight growth and melanin deposition in black-bone chickens. The genetic variations in growth traits, blackness traits, breast muscle transcriptome, and metabolism were compared between the Yanjin black-bone (YJ) chicken group ( n  = 20) and Jinling Partridge black-bone (JL) chicken group ( n  = 20). In addition, very high-melanin content (HB) individuals ( n  = 6) and very low-melanin content individuals (LB) ( n  = 6) were selected from the JL chicken group to investigate the melanin synthesis mechanism. Results Comparison between the breast muscle transcriptomes of YJ chickens and JL chickens, as well as between HB and LB of JL chickens, revealed that 81 common differentially expressed genes (DEGs) were significantly enriched in melanosomes, pigment particles, and melanogenesis pathways. Among them, four candidate genes, namely TYRP1, KIT, PRKCB and EDNRB2 , may be significantly associated with melanin production in black-bone chicken breast muscle. Also, 2 of the marker metabolites among the 16 common differential metabolites (DMs) identified, namely tetrahydrobiopterin (BH 4 ) and N-acetylneuraminic acid, significantly contribute to melanin synthesis in the breast muscle of black-bone chickens. Conclusion Our research presents complex regulatory networks of DEGs and DMs in melanin synthesis pathways. The results establish a basis for raising black-bone chickens with optimal melanin levels and offer a theoretical framework for investigating the mechanisms of melanin formation in these hens.

Abstract Plumage pigmentation plays critical roles in survival and reproductive success in birds, from providing camouflage and thermoregulation to mediating elaborate mating displays. The genetic and developmental origins of diverse plumage pigmentation patterns remain incompletely understood, in part, due to limited intraspecific variation and high levels of genetic divergence between distantly related species. Domestic avian species are more tractable models for understanding the genetic architecture of plumage pigmentation, but the relevance of domestic phenotypes to plumage patterns observed in the wild is not clear. Here, we used comparative genomic approaches to examine coding variation in EDNRB2, a candidate gene associated with loss of plumage melanin in several species, in representative genomes from a diverse array of wild and domestic birds. We found widespread coding variation in EDNRB2 and in other pigmentation genes with limited pleiotropic roles in development. We also found that EDNRB2-mediated melanin loss may play a critical role in establishing bright non-melanin plumage colors. This work highlights EDNRB2 as a key candidate gene for mediating the development of both interspecific and intraspecific plumage variation and demonstrates the applicability of findings in domestic species to understanding avian plumage patterning more broadly.

Strong ultraviolet (UV) radiation at high altitude imposes a serious selective pressure, which may induce skin pigmentation adaptation of indigenous populations. We conducted skin pigmentation phenotyping and genome-wide analysis of Tibetans in order to understand the underlying mechanism of adaptation to UV radiation. We observe that Tibetans have darker baseline skin color compared with lowland Han Chinese, as well as an improved tanning ability, suggesting a two-level adaptation to boost their melanin production. A genome-wide search for the responsible genes identifies GNPAT showing strong signals of positive selection in Tibetans. An enhancer mutation (rs75356281) located in GNPAT intron 2 is enriched in Tibetans (58%) but rare in other world populations (0 to 18%). The adaptive allele of rs75356281 is associated with darker skin in Tibetans and, under UVB treatment, it displays higher enhancer activities compared with the wild-type allele in in vitro luciferase assays. Transcriptome analyses of gene-edited cells clearly show that with UVB treatment, the adaptive variant of GNPAT promotes melanin synthesis, likely through the interactions of CAT and ACAA1 in peroxisomes with other pigmentation genes, and they act synergistically, leading to an improved tanning ability in Tibetans for UV protection.

The lateral hypothalamus (LH) controls energy balance. LH melanin-concentrating-hormone (MCH) and orexin/hypocretin (OH) neurons mediate energy accumulation and expenditure, respectively. MCH cells promote memory and appropriate stimulus-reward associations; their inactivation disrupts energy-optimal behaviour and causes weight loss. However, MCH cell dynamics during wakefulness are unknown, leaving it unclear if they differentially participate in brain activity during sensory processing. By fiberoptic recordings from molecularly defined populations of LH neurons in awake freely moving mice, we show that MCH neurons generate conditional population bursts. This MCH cell activity correlates with novelty exploration, is inhibited by stress and is inversely predicted by OH cell activity. Furthermore, we obtain brain-wide maps of monosynaptic inputs to MCH and OH cells, and demonstrate optogenetically that VGAT neurons in the amygdala and bed nucleus of stria terminalis inhibit MCH cells. These data reveal cell-type-specific LH dynamics during sensory integration, and identify direct neural controllers of MCH neurons. Hypothalamic neurons expressing melanin-concentrating-hormone (MCH) maintain body weight by orchestrating behaviour and metabolism, but little is known about their intrinsic regulation. Here, Gonzalez and colleagues reveal their behaviour-related dynamics during wakefulness, and map their brain-wide neural inputs.