RESUMEN

Corn snakes are emerging models for animal colouration studies. Here, we focus on the Terrazzo morph, whose skin pattern is characterized by stripes rather than blotches. Using genome mapping, we discover a disruptive mutation in the coding region of the Premelanosome protein (PMEL) gene. Our transcriptomic analyses reveal that PMEL expression is significantly downregulated in Terrazzo embryonic tissues. We produce corn snake PMEL knockouts, which present a comparable colouration phenotype to Terrazzo and the subcellular structure of their melanosomes and xanthosomes is also similarly impacted. Our single-cell expression analyses of wild-type embryonic dorsal skin demonstrate that all chromatophore progenitors express PMEL at varying levels. Finally, we show that in wild-type embryos PMEL-expressing cells are initially uniformly spread before forming aggregates and eventually blotches, as seen in the adults. In Terrazzo embryos, the aggregates fail to form. Our results provide insights into the mechanisms governing colouration patterning in reptiles.

Asunto(s)

Pigmentación de la Piel , Animales , Pigmentación de la Piel/genética , Serpientes/embriología , Serpientes/genética , Serpientes/metabolismo , Melanosomas/metabolismo , Regulación del Desarrollo de la Expresión Génica , Mutación , Cromatóforos/metabolismo , Fenotipo , Embrión no Mamífero/metabolismo , Análisis de la Célula Individual/métodos , Color , Piel/metabolismo , Piel/embriología , Piel/citología

RESUMEN

BACKGROUND: Melanin in the black-bone chicken's body is considered the material basis for its medicinal effects and is an economically important trait. Therefore, improving the melanin content is a crucial focus in the breeding process of black-bone chickens. Luning chickens are black-bone chickens, with black beaks, skin, and meat. To investigate the genetic diversity and molecular mechanisms of melanin deposition in Luning chickens, we conducted whole-genome resequencing to analyze their breeding history and identify candidate genes influencing their black phenotype, along with transcriptome sequencing of dorsal skin tissues of male Luning chickens. RESULTS: Population structure analysis revealed that Luning chickens tend to cluster independently and are closely related to Tibetan chickens. Runs of homozygosity analysis suggested potential inbreeding in the Luning chicken and Tibetan chicken population. By combining genetic differentiation index (Fst) and nucleotide diversity (θπ) ratios, we pinpointed selected regions associated with melanin deposition. Gene annotation identified 540 genes with the highest Fst value in LOC101750371 and LOC121108313, located on the 68.24-68.58 Mb interval of chromosome Z. Combining genomic and transcriptomic data, we identified ATP5E, EDN3, and LOC101750371 as candidate genes influencing skin color traits in black-bone chickens. CONCLUSIONS: This study characterized the evolutionary history of Luning chickens and preliminarily excavated candidate genes influencing the genetic mechanism of pigmentation in black-bone chickens, providing valuable insights for the study of animal melanin deposition.

Asunto(s)

Pollos , Melaninas , Secuenciación Completa del Genoma , Animales , Pollos/genética , Pollos/metabolismo , Melaninas/metabolismo , Melaninas/genética , Pigmentación de la Piel/genética , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple

RESUMEN

AIMS: Beyond the pivotal roles of the gut microbiome in initiating physiological processes and modulating genetic factors, a query persists: Can a single gene mutation alter the abundance of the gut microbiome community? Not only this, but the intricate impact of gut microbiome composition on skin pigmentation has been largely unexplored. METHODS AND RESULTS: Based on these premises, our study examines the abundance of lipase-producing gut microbes about differential gene expression associated with bile acid synthesis and lipid metabolism-related blood metabolites in red (whole wild) and white (whole white wild and SCARB1-/- mutant) Oujiang colour common carp. Following the disruption of the SCARB1 gene in the resulting mutant fish with white body colour (SCARB1-/-), there is a notable decrease in the abundance of gut microbiomes (Bacillus, Staphylococcus, Pseudomonas, and Serratia) associated with lipase production. This reduction parallels the downregulation seen in wild-type white body colour fish (WW), as contrasting to the wild-type red body colour fish (WR). Meanwhile, in SCARB1-/- fish, there was a downregulation noted not only at the genetic and metabolic levels but also a decrease in lipase-producing bacteria. This consistency with WW contrasts significantly with WR. Similarly, genes involved in the bile acid synthesis pathway, along with blood metabolites related to lipid metabolism, exhibited downregulation in SCARB1-/- fish. CONCLUSIONS: The SCARB1 knockout gene blockage led to significant alterations in the gut microbiome, potentially influencing the observed reduction in carotenoid-associated skin pigmentation. Our study emphasizes that skin pigmentation is not only impacted by genetic factors but also by the gut microbiome. Meanwhile, the gut microbiome's adaptability can be rapidly shaped and may be driven by specific single-gene variations.

Asunto(s)

Carpas , Microbioma Gastrointestinal , Pigmentación de la Piel , Animales , Carpas/microbiología , Pigmentación de la Piel/genética , Lipasa/genética , Lipasa/metabolismo , Mutación , Metabolismo de los Lípidos , Ácidos y Sales Biliares/metabolismo , Bacterias/genética , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Bacterias/clasificación

RESUMEN

The Greying with age phenotype in horses involves loss of hair pigmentation whereas skin pigmentation is not reduced, and a predisposition to melanoma. The causal mutation was initially reported as a duplication of a 4.6 kb intronic sequence in Syntaxin 17. The speed of greying varies considerably among Grey horses. Here we demonstrate the presence of two different Grey alleles, G2 carrying two tandem copies of the duplicated sequence and G3 carrying three. The latter is by far the most common allele, probably due to strong selection for the striking white phenotype. Our results reveal a remarkable dosage effect where the G3 allele is associated with fast greying and high incidence of melanoma whereas G2 is associated with slow greying and low incidence of melanoma. The copy number expansion transforms a weak enhancer to a strong melanocyte-specific enhancer that underlies hair greying (G2 and G3) and a drastically elevated risk of melanoma (G3 only). Our direct pedigree-based observation of the origin of a G2 allele from a G3 allele by copy number contraction demonstrates the dynamic evolution of this locus and provides the ultimate evidence for causality of the copy number variation of the 4.6 kb intronic sequence.

Asunto(s)

Alelos , Variaciones en el Número de Copia de ADN , Color del Cabello , Intrones , Melanoma , Proteínas Qa-SNARE , Caballos/genética , Animales , Variaciones en el Número de Copia de ADN/genética , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo , Melanoma/genética , Melanoma/veterinaria , Melanoma/epidemiología , Intrones/genética , Color del Cabello/genética , Linaje , Masculino , Femenino , Fenotipo , Incidencia , Enfermedades de los Caballos/genética , Enfermedades de los Caballos/epidemiología , Pigmentación de la Piel/genética

RESUMEN

The ultraviolet (UV) radiation triggers a pigmentation response in human skin, wherein, melanocytes rapidly activate divergent maturation and proliferation programs. Using single-cell sequencing, we demonstrate that these 2 programs are segregated in distinct subpopulations in melanocytes of human and zebrafish skin. The coexistence of these 2 cell states in cultured melanocytes suggests possible cell autonomy. Luria-Delbrück fluctuation test reveals that the initial establishment of these states is stochastic. Tracking of pigmenting cells ascertains that the stochastically acquired state is faithfully propagated in the progeny. A systemic approach combining single-cell multi-omics (RNA+ATAC) coupled to enhancer mapping with H3K27 acetylation successfully identified state-specific transcriptional networks. This comprehensive analysis led to the construction of a gene regulatory network (GRN) that under the influence of noise, establishes a bistable system of pigmentation and proliferation at the population level. This GRN recapitulates melanocyte behaviour in response to external cues that reinforce either of the states. Our work highlights that inherent stochasticity within melanocytes establishes dedicated states, and the mature state is sustained by selective enhancers mark through histone acetylation. While the initial cue triggers a proliferation response, the continued signal activates and maintains the pigmenting subpopulation via epigenetic imprinting. Thereby our study provides the basis of coexistence of distinct populations which ensures effective pigmentation response while preserving the self-renewal capacity.

Asunto(s)

Proliferación Celular , Redes Reguladoras de Genes , Melanocitos , Pigmentación de la Piel , Pez Cebra , Melanocitos/metabolismo , Pez Cebra/genética , Animales , Humanos , Pigmentación de la Piel/genética , Pigmentación de la Piel/fisiología , Procesos Estocásticos , Diferenciación Celular/genética , Histonas/metabolismo , Acetilación , Rayos Ultravioleta , Análisis de la Célula Individual , Pigmentación/genética , Elementos de Facilitación Genéticos/genética , Epigénesis Genética , Piel/metabolismo , Piel/citología

RESUMEN

The gut microbiome plays a key role in regulating the gut-skin axis, and host genetics partially influence this regulation. The study investigated the role of gut microbiota and host genetics in the gut-skin axis, focusing on the unusual "coffee-like" color phenotype observed in TYRP1 mutant Oujiang Color Common Carp. We employed comparative high-throughput omics data from wild-type and mutant fish to quantify the influence of both genetics and gut microbes on skin transcriptomic expression and blood metabolites. We found 525 differential metabolites (DMs) and 45 distinct gut microbial genera in TYRP1 mutant fish compared to wild type. Interaction and causal mediation analyses revealed a complex interplay. The TYRP1 mutation likely triggers an inflammatory pathway involving Acinetobacter bacteria, Leukotrience-C4 and Spermine. This inflammatory response appears to be counterbalanced by an anti-inflammatory cardiovascular genetic network. The net effect is the upregulation of COMT, PLG, C2, C3, F10, TDO2, MHC1, and SERPINF2, leading to unusual coffee-like coloration. This study highlights the intricate interplay between gut microbiota, host genetics, and metabolic pathways in shaping complex phenotypes.

Asunto(s)

Carpas , Microbioma Gastrointestinal , Mutación , Pigmentación de la Piel , Animales , Carpas/genética , Carpas/microbiología , Carpas/metabolismo , Pigmentación de la Piel/genética , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Transcriptoma , Piel/metabolismo , Piel/microbiología

RESUMEN

Retrotransposons comprise about 45% of the human genome1, but their contributions to human trait variation and evolution are only beginning to be explored2,3. Here, we find that a sequence of SVA retrotransposon insertions in an early intron of the ASIP (agouti signaling protein) gene has probably shaped human pigmentation several times. In the UK Biobank (n = 169,641), a recent 3.3-kb SVA insertion polymorphism associated strongly with lighter skin pigmentation (0.22 [0.21-0.23] s.d.; P = 2.8 × 10-351) and increased skin cancer risk (odds ratio = 1.23 [1.18-1.27]; P = 1.3 × 10-28), appearing to underlie one of the strongest common genetic influences on these phenotypes within European populations4-6. ASIP expression in skin displayed the same association pattern, with the SVA insertion allele exhibiting 2.2-fold (1.9-2.6) increased expression. This effect had an unusual apparent mechanism: an earlier, nonpolymorphic, human-specific SVA retrotransposon 3.9 kb upstream appeared to have caused ASIP hypofunction by nonproductive splicing, which the new (polymorphic) SVA insertion largely eliminated. Extended haplotype homozygosity indicated that the insertion allele has risen to allele frequencies up to 11% in European populations over the past several thousand years. These results indicate that a sequence of retrotransposon insertions contributed to a species-wide increase, then a local decrease, of human pigmentation.

Asunto(s)

Proteína de Señalización Agouti , Retroelementos , Pigmentación de la Piel , Humanos , Retroelementos/genética , Proteína de Señalización Agouti/genética , Pigmentación de la Piel/genética , Mutagénesis Insercional , Alelos , Neoplasias Cutáneas/genética , Genoma Humano , Intrones/genética

Asunto(s)

Neoplasias Cutáneas , Pigmentación de la Piel , Humanos , Neoplasias Cutáneas/genética , Pigmentación de la Piel/genética , Predisposición Genética a la Enfermedad , Mutagénesis Insercional , Factores de Riesgo , Elementos Transponibles de ADN/genética

RESUMEN

Hyperpigmented dermatoses are characterized by increased skin pigmentation caused by genetic, environmental factors and inflammation, which lasts a long time and is difficult to treat. Ultraviolet (UV), especially ultraviolet B (UVB), is the primary external factor inducing skin pigmentation. However, the specific regulatory mechanisms are not fully understood. Through analysis of GEO datasets from four UV-exposed skin cell/tissue samples, we found that TRPS1 is the only gene differentially expressed in multiple datasets (GSE22083, GSE67098 and GSE70280) and highly positively correlated with the expression of key melanogenesis genes. Consistently, we observed that TRPS1 is highly expressed in sun-exposed skin tissues compared to non-exposed skin. Additionally, the expression of TRPS1 was also significantly upregulated after UVB irradiation in isolated skin tissues and melanocytes, while knockdown of TRPS1 expression inhibited the UVB-induced melanogenesis. Further research revealed that overexpression of TRPS1 increased melanin content and tyrosinase activity in MNT1 cells, as well as upregulated the expression levels of key melanogenesis genes (MITF, TYR, TYRP1, DCT). In contrast, inhibition of TRPS1 expression showed the opposite effect. Moreover, we found that TRPS1 can bind to the promoter region of MITF, inhibiting the expression of MITF can antagonize the melanogenesis induced by TRPS1. In conclusion, UVB-induced TRPS1 promotes melanogenesis by activating the transcriptional activity of MITF.

Asunto(s)

Melanocitos , Factor de Transcripción Asociado a Microftalmía , Proteínas Represoras , Pigmentación de la Piel , Rayos Ultravioleta , Humanos , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica/efectos de la radiación , Melaninas/biosíntesis , Melaninas/metabolismo , Melanocitos/metabolismo , Melanocitos/efectos de la radiación , Melanocitos/patología , Factor de Transcripción Asociado a Microftalmía/metabolismo , Factor de Transcripción Asociado a Microftalmía/genética , Regiones Promotoras Genéticas , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Piel/metabolismo , Piel/efectos de la radiación , Piel/patología , Pigmentación de la Piel/efectos de la radiación , Pigmentación de la Piel/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción Genética/efectos de la radiación , Rayos Ultravioleta/efectos adversos

RESUMEN

BACKGROUND: Neither a TYRP1-mediated highly conserved genetic network underlying skin color towards optimum defense nor the pathological tendency of its mutation is well understood. The Oujiang Color Common Carp (Cyprinus carpio var. color) as a model organism, offering valuable insights into genetics, coloration, aquaculture practices, and environmental health. Here, we performed a comparative skin transcriptome analysis on TYRP1 mutant and wild fishes by applying a conservative categorical approach considering different color phenotypes. RESULTS: Our results reveal that an unusual color phenotype may be sensitized with TYRP1 mutation as a result of upregulating several genes related to an anti-inflammatory autoimmune system in response to the COMT-mediated catecholamine neurotransmitters in the skin. Particularly, catecholamines-derived red/brown, red with blue colored membrane attack complex, and brown/grey colored reduced eumelanin are expected to be aggregated in the regenerated cells. CONCLUSIONS: It is, thus, concluded that the regenerated cells with catecholamines, membrane attack complex, and eumelanin altogether may contribute to the formation of the unusual (coffee-like) color phenotype in TYRP1 mutant.

Asunto(s)

Carpas , Redes Reguladoras de Genes , Mutación , Pigmentación de la Piel , Animales , Carpas/genética , Pigmentación de la Piel/genética , Fenotipo , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Perfilación de la Expresión Génica , Transcriptoma

RESUMEN

Southern flounder skin pigmentation is a critical phenotypic characteristic for this species' survival in the natural environment. Normal pigmentation allows rapid changes of color for concealment to capture prey and UV light protection. In contrast, highly visible hypopigmented pseudo-albinos exhibit a compromised immune system and are vulnerable to predation, sensitive to UV exposure, and likely have poor survival in the wild. Skin and brain tissue samples from normally pigmented and hypopigmented individuals were analyzed with next-generation RNA sequencing. A total of 1,589,613 transcripts were used to identify 952,825 genes to assemble a de novo transcriptome, with 99.43% of genes mapped to the assembly. Differential gene expression and gene enrichment analysis of contrasting tissues and phenotypes revealed that pseudo-albino individuals appeared more susceptible to environmental stress, UV light exposure, hypoxia, and osmotic stress. The pseudo-albinos' restricted immune response showed upregulated genes linked to cancer development, signaling and response, skin tissue formation, regeneration, and healing. The data indicate that a modified skin collagen structure likely affects melanocyte differentiation and distribution, generating the pseudo-albino phenotype. In addition, the comparison of the brain transcriptome revealed changes in myelination and melanocyte stem cell activity, which may indicate modified brain function, reduced melanocyte migration, and impaired vision.

Asunto(s)

Encéfalo , Lenguado , Hipopigmentación , Pigmentación de la Piel , Piel , Transcriptoma , Animales , Encéfalo/metabolismo , Encéfalo/patología , Piel/metabolismo , Piel/patología , Hipopigmentación/genética , Lenguado/genética , Pigmentación de la Piel/genética , Perfilación de la Expresión Génica , Rayos Ultravioleta/efectos adversos

RESUMEN

Skin pigmentation is negatively associated with circulating vitamin D (VD) concentration. Therefore, genetic factors involved in skin pigmentation could influence the risk of vitamin D deficiency (VDD). We evaluated the impact genetic variants related to skin pigmentation on VD in Mexican population. This cross-sectional analysis included 848 individuals from the Health Worker Cohort Study (ratio males to females ~ 1:3). Eight genetic variants: rs16891982 (SLC45A2), rs12203592 (IRF4), rs1042602 and rs1126809 (TYR), rs1800404 (OCA2), rs12913832 (HERC2), rs1426654 (SLC24A5), and rs2240751 (MFSD12); involved in skin pigmentation were genotyped. Skin pigmentation was assessed by self-report. Linear and logistic regression were used to assess the association between the variants of interest and VD and VDD, as appropriate. In our study, eight genetic variants were associated with skin pigmentation. A genetic risk score built with the variants rs1426654 and rs224075 was associated with lower VD levels (ß = - 1.38, 95% CI - 2.59, - 0.17, p = 0.025). Nevertheless, when examining gene-gene interactions, we observed that rs2240751 × rs12203592 were associated with VD levels (P interaction = 0.021). Whereas rs2240751 × rs12913832 (P interaction = 0.0001) were associated with VDD. Our results suggest that skin pigmentation-related gene variants are associated with lower VD levels in Mexican population. These results underscore the importance of considering genetic interactions when assessing the impact of genetic polymorphisms on VD levels.

Asunto(s)

Polimorfismo de Nucleótido Simple , Pigmentación de la Piel , Deficiencia de Vitamina D , Vitamina D , Humanos , Masculino , Femenino , México , Pigmentación de la Piel/genética , Deficiencia de Vitamina D/genética , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Vitamina D/sangre , Vitamina D/análogos & derivados , Adulto , Persona de Mediana Edad , Estudios Transversales , Predisposición Genética a la Enfermedad

RESUMEN

Reptilian skin coloration is spectacular and diverse, yet little is known about the ontogenetic processes that govern its establishment and the molecular signaling pathways that determine it. Here, we focus on the development of the banded pattern of leopard gecko hatchlings and the transition to black spots in the adult. With our histological analyses, we show that iridophores are present in the white and yellow bands of the hatchling and they gradually perish in the adult skin. Furthermore, we demonstrate that melanophores can autonomously form spots in the absence of the other chromatophores both on the regenerated skin of the tail and on the dorsal skin of the Mack Super Snow (MSS) leopard geckos. This color morph is characterized by uniform black coloration in hatchlings and black spots in adulthood; we establish that their skin is devoid of xanthophores and iridophores at both stages. Our genetic analyses identified a 13-nucleotide deletion in the PAX7 transcription factor of MSS geckos, affecting its protein coding sequence. With our single-cell transcriptomics analysis of embryonic skin, we confirm that PAX7 is expressed in iridophores and xanthophores, suggesting that it plays a key role in the differentiation of both chromatophores. Our in situ hybridizations on whole-mount embryos document the dynamics of the skin pattern formation and how it is impacted in the PAX7 mutants. We hypothesize that the melanophores-iridophores interactions give rise to the banded pattern of the hatchlings and black spot formation is an intrinsic capacity of melanophores in the postembryonic skin.

Asunto(s)

Cromatóforos , Lagartos , Pigmentación de la Piel , Animales , Lagartos/genética , Lagartos/metabolismo , Lagartos/fisiología , Cromatóforos/metabolismo , Pigmentación de la Piel/genética , Pigmentación de la Piel/fisiología , Piel/metabolismo , Melanóforos/metabolismo , Regulación del Desarrollo de la Expresión Génica

RESUMEN

Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual's genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations.

Asunto(s)

Polimorfismo de Nucleótido Simple , Autoinforme , Pigmentación de la Piel , Humanos , Brasil , Pigmentación de la Piel/genética , Masculino , Femenino , Adulto , Población Blanca/genética , Población Urbana , Población Negra/genética , Grupos Raciales/genética , Persona de Mediana Edad , Genética de Población

RESUMEN

Opsins are a class of transmembrane proteins encoded by opsin genes, and they play a variety of functional roles. Short wavelength-sensitive opsin 2 (sws2), one of the five classes of visual opsin genes, mainly senses blue light. Previous research has indicated that sws2 is essential for melanocyte formation in fish; however, its specific role in skin color differentiation remains to be elucidated. Here, we identified the sws2 gene in a prized reef-dwelling fish, Plectropomus leopardus. The full-length P. leopardus sws2 gene encodes a protein consisting of 351 amino acids, and exhibits substantial homology with other fish species. The expression of the sws2 gene was widespread across P. leopardus tissues, with high expression in eye and skin tissues. Through immunohistochemistry and in situ hybridization analyses, we discovered that the sws2 gene was primarily localized in the rod and cone cells of the retina, and epidermal cells of the skin. Furthermore, dsRNA interference was used for sws2 gene knockdown in living P. leopardus to elucidate its function in skin color differentiation. Black-color-related genes, melanin contents, and tyrosinase activity in the skin significantly decreased after sws2 knockdown (p < 0.05), but red-color-related genes and carotenoid and lutein contents significantly increased (p < 0.05). Retinoic acid injection produced the opposite results. Our results suggested that the sws2 gene influences P. leopardus skin color regulation by affecting vitamin synthesis and melanin-related gene expression levels. This study establishes a foundation for elucidating the molecular mechanisms by which sws2 regulates melanocyte formation in fish skin.

Asunto(s)

Melaninas , Piel , Tretinoina , Animales , Melaninas/biosíntesis , Melaninas/metabolismo , Tretinoina/metabolismo , Piel/metabolismo , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Pigmentación de la Piel/genética , Opsinas/metabolismo , Opsinas/genética , Regulación de la Expresión Génica

RESUMEN

Observational studies have revealed associations between various dietary factors and skin conditions. However, the causal relationship between diet and skin condition is still unknown. Data on 17 dietary factors were obtained from the UK Biobank. Data on four skin conditions were derived from the UK Biobank and another large-scale GWAS study. Genetic predictions suggested that the intake of oily fish was associated with a lower risk of skin aging (OR: 0.962, P = 0.036) and skin pigmentation (OR: 0.973, P = 0.033); Tea intake was associated with a lower risk of skin pigmentation (OR: 0.972, P = 0.024); Salad/raw vegetables intake was associated with a lower risk of keratinocyte skin cancer (OR: 0.952, P = 0.007). Coffee intake was associated with increased risk of skin aging (OR: 1.040, P = 0.028); Pork intake was associated with increased risk of skin aging (OR: 1.134, P = 0.020); Beef intake was associated with increased risk of cutaneous melanoma (OR: 1.013, P = 0.016); Champagne plus white wine intake was associated with increased risk of cutaneous melanoma (OR: 1.033, P = 0.004); Bread intake was associated with increased risk of keratinocyte skin cancer (OR: 1.026, P = 0.013). Our study results indicate causal relationships between genetically predicted intake of oily fish, tea, salad/raw vegetables, coffee, pork, beef, champagne plus white wine, and bread and skin conditions.

Asunto(s)

Dieta , Análisis de la Aleatorización Mendeliana , Neoplasias Cutáneas , Humanos , Dieta/efectos adversos , Dieta/estadística & datos numéricos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología , Envejecimiento de la Piel/genética , Pigmentación de la Piel/genética , Café/efectos adversos , Estudio de Asociación del Genoma Completo , Reino Unido/epidemiología , Té/efectos adversos , Factores de Riesgo

RESUMEN

Evidence for adaptation of human skin color to regional ultraviolet radiation suggests shared and distinct genetic variants across populations. However, skin color evolution and genetics in East Asians are understudied. We quantified skin color in 48,433 East Asians using image analysis and identified associated genetic variants and potential causal genes for skin color as well as their polygenic interplay with sun exposure. This genome-wide association study (GWAS) identified 12 known and 11 previously unreported loci and SNP-based heritability was 23-24%. Potential causal genes were determined through the identification of nonsynonymous variants, colocalization with gene expression in skin tissues, and expression levels in melanocytes. Genomic loci associated with pigmentation in East Asians substantially diverged from European populations, and we detected signatures of polygenic adaptation. This large GWAS for objectively quantified skin color in an East Asian population improves understanding of the genetic architecture and polygenic adaptation of skin color and prioritizes potential causal genes.

Asunto(s)

Estudio de Asociación del Genoma Completo , Herencia Multifactorial , Polimorfismo de Nucleótido Simple , Pigmentación de la Piel , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adaptación Fisiológica/genética , Mapeo Cromosómico , Herencia Multifactorial/genética , Sitios de Carácter Cuantitativo/genética , Pigmentación de la Piel/genética , Rayos Ultravioleta , Pueblos del Este de Asia

RESUMEN

As modern humans ventured out of Africa and dispersed around the world, they faced novel environmental challenges that led to geographic adaptations including skin colour. Over the long history of human evolution, skin colour has changed dramatically, showing tremendous diversity across different geographical regions, for example, the majority of individuals from the expansive lands of Africa have darker skin, whereas the majority of people from Eurasia exhibit lighter skin. What adaptations did lighter skin confer upon modern humans as they migrated from Africa to Eurasia? What genetic mechanisms underlie the diversity of skin colour observed in different populations? In recent years, scientists have gradually gained a deeper understanding of the interactions between pigmentation gene and skin colour through population-based genomic studies of different groups around the world, particularly in East Asia and Africa. In this review, we summarize our current understanding of 26 skin colour-related pigmentation genes and 48 SNPs that influence skin colour. Important pigmentation genes across three major populations are described in detail: MFSD12, SLC24A5, PDPK1 and DDB1/CYB561A3/TMEM138 influence skin colour in African populations; OCA2, KITLG, SLC24A2, GNPAT and PAH are key to the evolution of skin pigmentation in East Asian populations; and SLC24A5, SLC45A2, TYR, TYRP1, ASIP, MC1R and IRF4 significantly contribute to the lightening of skin colour in European populations. We summarized recent findings in genomic studies of skin colour in populations that implicate diverse geographic environments, local adaptation among populations, gene flow and multi-gene interactions as factors influencing skin colour diversity.

Asunto(s)

Polimorfismo de Nucleótido Simple , Pigmentación de la Piel , Pigmentación de la Piel/genética , Humanos , Fenotipo , Evolución Biológica , Adaptación Fisiológica/genética , Genética de Población , África , Adaptación Biológica/genética

RESUMEN

Pigmentation genes expressed in skin, body muscle and tail of Thai-flag compared with Blue, White and Red varieties of Siamese fighting fish Betta splendens were identified. In total, 22,919 new unigenes were found. Pearson correlation and PCA analysis revealed that expression profiles of genes in muscle, skin and tail across solid color variety were similar. In contrast, those in skin and red tail part of Thai-flag were closely related but they showed different expression profiles with the white tail part. Moreover, 21,347-64,965 SNPs were identified in exonic regions of identified genes. In total, 28,899 genes were differentially expressed between paired comparisons of libraries where 13,907 genes (48.12 %) were upregulated and 14,992 genes (51.88 %) were downregulated. DEGs between paired libraries were 106-5775 genes relative to the compared libraries (56-2982 and 50-2782 for upregulated and downregulated DEGs). Interestingly, 432 pigmentation genes of B. splendens were found. Of these, 297 DEGs showed differential expression between varieties. Many DEGs in melanogenesis (Bsmcr1r, Bsmcr5r, and Bsslc2a15b), tyrosine metabolism (Bstyr, Bstyrp1b and Bsdct), stripe repressor (BsAsip1 and BsAsip2b), pteridine (Bsgch2) and carotenoid (BsBco2) biosynthesis were downregulated in the Thai-flag compared with solid color varieties. Expression of Bsbco1l, Bsfrem2b, Bskcnj13, Bszic2a and Bspah in skin, muscle and tail of Thai-flag, Blue, Red and White varieties was analyzed by qRT-PCR and revealed differential expression between fish varieties and showed anatomical tissue-preferred expression patterns in the same fish variety. The information could be applied to assist genetic-based development of new B. splendens varieties in the future.

Asunto(s)

Pigmentación , Animales , Proteínas de Peces/genética , Peces/genética , Perfilación de la Expresión Génica , Músculos/metabolismo , Pigmentación/genética , Polimorfismo de Nucleótido Simple , Piel/metabolismo , Pigmentación de la Piel/genética , Cola (estructura animal) , Tailandia , Transcriptoma

RESUMEN

The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments. East Asians are ideal populations for studying skin color evolution because of the complex environment of East Asia. Here, we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase (PAH) in light-skinned Han Chinese individuals. The intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males (P < 0.05). In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for PAH. However, the derived T allele (the major allele in East Asians) of rs10778203 decreases the binding activity of transcription factors and enhancer activity. Meanwhile, the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish embryos. Furthermore, rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B (UVB) treatment. Collectively, PAH is a potential pigmentation gene that regulates skin tanning ability. Natural selection has enriched the adaptive allele, resulting in weakened tanning ability in East Asians, suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.

Asunto(s)

Pueblos del Este de Asia , Pigmentación de la Piel , Animales , Humanos , Masculino , Alelos , Animales Modificados Genéticamente , Evolución Biológica , Pueblos del Este de Asia/genética , Melaninas/metabolismo , Melaninas/genética , Mutación , Fenilalanina Hidroxilasa/genética , Fenilalanina Hidroxilasa/metabolismo , Polimorfismo de Nucleótido Simple , Selección Genética , Pigmentación de la Piel/genética , Pigmentación de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Pez Cebra/genética