Unraveling the population genetic structure and identifying candidate genes for dorsal plumage color in Liangshan Yanying chickens.

ABSTRACT Hyperpigmentation is a common skin condition resulting from uncontrolled melanin production or accumulation. Commercial skin-whitening products have been reported to cause undesirable skin effects, limiting safe treatment options. Microalgae are increasingly explored as sustainable sources for cosmetic applications due to their diverse bioactive properties and versatility. Chlorella vulgaris, a green microalga, is regarded as a promising source of beneficial compounds, particularly in cosmeceuticals. In this study, pigmentation-related targets were identified from public databases, and network pharmacology techniques were employed, including protein–protein interaction (PPI) network construction using STRING and visualization in Cytoscape. Enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The interactions between hub targets and C. vulgaris compounds retrieved from PubChem were investigated via molecular docking and molecular dynamics simulations. Hub genes TYRP1, TYR, TP53, SLC45A2, CTNNB1, and MC1R were identified as significant regulators of melanocyte differentiation and melanogenesis-associated pathways. Molecular docking highlighted four hit compounds namely 7,22-ergostadienol acetate (CID: 14056082), dehydroergosterol acetate (CID: 69827569), ergosterol acetate (CID: 6436903), and [(3S,10S,13 R,14 R,17 R)-17-[(E,2 R,5 R)-5-ethyl-6-methylhept-3-en-2-yl]-10,13-dimethyl 2,3,4,12,14,15,16,17-octahydro-1 H-cyclopenta[a]phenanthren-3-yl] acetate (PubChem CID: 162856537), which showed favourable binding affinities with the core gene targets. Molecular dynamics revealed that these compounds could bind stably to SLC45A2, CTNNB1, and MC1R, suggesting potential depigmenting effects of C. vulgaris. While these findings provide a theoretical framework for microalgae-derived depigmentation agents, the study is based solely on in silico predictions and relies on currently available compound–target databases, which may not encompass the full chemical diversity of C. vulgaris. Therefore, further validation through phytochemical characterization, in vitro assays, and in vivo studies is essential to confirm the therapeutic potential of these compounds for pigmentation-related skin disorders.

Novel miR-290 regulates melanogenesis in Liancheng white ducks via the PI3K/AKT signaling pathway

Domestic Baroque donkeys are popular animals in many European parks and zoos. Although their cream coat color is very charismatic, the underlying genetics is still undiscovered. Addressing this question, a candidate approach was used to search for the causative mutation.Considering the knowledge from domestic horses, the Solute Carrier Family 45 Member 2 (SLC45A2) was identified as the most promising candidate. Samples from 77 domesticated donkeys, 11 wild equids, 1 mule and 2 domestic horses were included in comparison. All exons and the flanking intron sequences of the SLC45A2 were sequenced (2774bp).Sequence comparison revealed that a mutation found exclusively in exon 7 transmembrane region 11 (c.1457C>T; p.Ala486Val) is very likely responsible for the charismatic coat color phenotype in Baroque donkeys. Family studies produced evidence for an autosomal recessive mode of inheritance. Since the coat color in Baroque donkeys varies from almost white to gold, the question remains whether the base coloration, which in mammals is regulated by the ASIP and MC1R genes, also have an impact but no remarkable mutations were found in Baroque donkeys.

Background and objectiveCoat color is an important economic trait in animal husbandry and plays a crucial role in the adaptability of animal. As a key economic trait in high-altitude areas, the genetic mechanisms regulating coat color in Tibetan sheep are not fully understood.MethodsIn order to explore the genetic basis of coat color in Tibetan sheep, this study focused on white-coated Plateau Tibetan sheep (PT) and black-coated Guinan black fur sheep (GB). Using whole genome sequencing (10× coverage), transcriptomic analysis, Sanger sequencing, and protein structure prediction to identify candidate genes and molecular markers associated with coat color.ResultsIn this study, a total of 9.28 million SNPs were annotated from whole-genome sequencing. Compared with the white-coated PT sheep, the skin transcriptome of black-coated GB sheep exhibited 659 up-regulated and 426 down-regulated genes. MC1R, MITF, and KIT were identified as candidate genes for the coat color of Tibetan sheep. Through Sanger sequencing of all exons of these genes and association analysis with coat color phenotypes, we found that 8 of 12 SNPs were significantly associated with coat color in Tibetan sheep. The coat color of individuals with heterozygous or homozygous mutations in both SNPs (rs3508196008 and rs409651063) in the MC1R gene were black. These two SNPs were likely to not cause loss or alteration of protein function, but rather affected the coat color of Tibetan sheep by regulating gene transcription and expression levels, and can be applied as molecular markers to regulate coat color in Tibetan sheep.ConclusionTwo molecular markers (rs3508196008 and rs409651063) in the MC1R gene regulating Tibetan coat color were identified through selective sweep analysis, transcriptome, Sanger sequencing, and the genetic mechanism of coat color was analyzed, which provided new insights for the genetics of coat color in Tibetan sheep, and provided effective markers and technical support for molecular breeding.

BackgroundMelanism in wild felids represents an intriguing evolutionary trait, potentially advantageous under specific ecological conditions, but the genetic basis of this phenotype remains unclear in many populations. Here, we explored melanism in the Indian leopard (Panthera pardus fusca) by integrating whole-genome sequencing with evolutionary and structural analyses.ResultsWe identified a single-point mutation (p.C117F) in the agouti signalling protein (ASIP) gene. Evolutionary analyses indicated signs of positive selection acting on the ASIP locus, while codon usage patterns revealed no impairment in translational efficiency. Computational predictions (SIFT, PROVEAN) classified the mutation as functionally damaging. Structural modelling combined with molecular dynamics simulations revealed significant disruptions in the stability, helical content, and receptor-binding affinity of the mutated ASIP protein compared to the wild type. The mutation notably diminished ASIP’s inhibitory interaction with melanocortin-1 receptor (MC1R), which is crucial for melanogenesis regulation. Machine-learning models differentiated between mutant and wild-type protein structures by analysing molecular features.ConclusionsOur results support the conclusion that the p.C117F mutation significantly contributes to melanism in Indian leopards, shedding new light on this trait’s molecular underpinnings and evolutionary history. This study identifies the p.C117F mutation as a key driver of melanism in leopards of the Indian subcontinent, providing mechanistic insight into the evolution of complex phenotypes in non-model species.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12864-025-12227-z.

Glabridin-encapsulated liposomes targeting melanocytes through the melanocortin 1 receptor.

3, 7-dihydroxy-2, 4-dimethoxyphenanthrene protects against UVB-induced skin hyperpigmentation via antioxidant and anti-melanogenic mechanisms.

Ultraviolet-tyrosinase cascade caged antisense oligonucleotide for precise treatment of hyperpigmentation.

Equid herpesvirus (EHV) 1 and -4 are common viral pathogens of horses that can cause upper respiratory disease, neurological disease, abortion, and death. As characteristic alphaherpesviruses, both EHV-1 and EHV-4 can establish latency, resulting in a lifelong carrier state in infected animals. Here we describe the development and validation of a rapid and sensitive multiplex real-time PCR assay (EHV1-4MP) that simultaneously detects EHV-1 and EHV-4 and includes an endogenous internal control - melanocortin 1 receptor (MC1R) - targeting the equid genome. The EHV1-4MP assay analytical sensitivity was determined to be approximately two copies for EHV-1, four copies for EHV-4, and 10 copies for the equid MC1R gene per reaction. Analytical specificity was determined using a panel of 28 equine respiratory pathogens and commensal equine microorganisms. The EHV1-4MP assay detected reference and clinical isolates of EHV-1 and EHV-4, and did not detect other equid herpesviruses such as EHV-2, EHV-3, EHV-5, or several other viral and bacterial pathogens of horses. Importantly, the EHV1-4MP assay developed here has improved specificity compared to existing assays and is able to exclude the closely related EHV-3, EHV-8, and EHV-9 viruses. Diagnostic performance was evaluated using 60 clinical samples including upper respiratory swabs and washes, blood, placenta, lung, and brain. The EHV1-4MP assay results were in 100% concordance with singleplex EHV-1 and EHV-4 assays. Our results demonstrate that the EHV1-4MP real-time assay developed here offers rapid, sensitive, and simultaneous detection of EHV-1 and EHV-4.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-22043-w.

Abstract Dexter cattle are genotyped for variants in the melanocortin 1 receptor (MC1R) gene, which determines black (ED) or red (E+ or e) coat color, as well as for a previously identified Dexter-specific variant of tyrosinase related protein 1 (TYRP1) that dilutes black to dun. Dexter cattle lacking the dun TYRP1 recessive genotype (bb) have been reported with an unexpected dark dun/chocolate (CD) or light dun/cream (CL) coat color. These unclassified coat colors occur at low frequency within the current Dexter cattle population. Based on observed inheritance patterns, we hypothesized a novel recessive genotype is causative of CD on a black background and CL on a red background. Whole genome sequence (WGS) data were collected from three chocolate animals, one cream animal, and one black calf of a chocolate dam. Data were mapped to the UCD-ARS1.2 genome and variants called. Combining these genotypes with those of 226 multibreed control cattle, a SnpSift case control analysis was conducted. 161 genomic variants fit the proposed hypothesis of homozygous recessive inheritance and were located within a 1.8 Mb segment of Chromosome 20. Two of those variants, when queried against a WGS database of over 5,500 cattle, were not present in other cattle. Only one of those variants had a predicted impact on gene function. The identified missense variant was in the solute carrier family 45 member 2 (SLC45A2) gene. DNA from over 190 Dexter cattle samples were screened by Sanger sequencing for the candidate SLC45A2 variant, as well as genotyped for known variation in MC1R, and TYRP1. Supporting our hypothesis, all cattle expressing the CL phenotype had two copies of the SLC45A2 variant on a red background and expressed the CD phenotype on a black background. There was no apparent coat color change in cattle heterozygous for the SLC45A2 variant, confirming a recessive mode of inheritance. The SLC45A2 (membrane-associated transporter protein; MATP and absent in melanoma 1; AIM1) protein has previously been shown to regulate coat, eye, and skin color in multiple species, including cattle, humans, horses, and mice. SLC45A2 plays a role in neutralizing pH of melanosomes to promote tyrosinase activity during stages III-IV of melanogenesis. An amino acid change in the SLC45A2 protein resulting from this mutation could potentially create an acidic environment, suppressing eumelanin synthesis. At present, no adverse consequences associated with this SLC45A2 variant in Dexter cattle have been identified. Testing for the SLC45A2 variant in Dexter cattle can be a valuable resource for Dexter breeders interested in coat color.

Pigmentation in mammalian hair follicles is governed in part by interactions between agouti signalling protein (ASIP) and the melanocortin 1 receptor (MC1R). The most common coat colours in mammals result from alternating bands of dark eumelanin and light phaeomelanin within individual hair shafts. However, coats dominated by a single melanin have arisen several times. Here, we examine the genetic basis of two instances in marsupials: a melanistic morph of the eastern quoll (Dasyurus viverrinus) found at high frequency in the wild, and a rare case of fixed xanthism in the marsupial moles. In eastern quolls, we identify a deletion encompassing the ASIP start codon which was found to be homozygous only in the melanistic animals examined. This mutation appears to be convergent with that recently discovered in its dark-coated relative, the Tasmanian devil (Sarcophilus harrisii). Conversely, we show that a non-sense mutation which severely truncates MC1R in the southern marsupial mole (Notoryctes typhlops) is a candidate driver of its pale-yellow coat. Together with other recent findings, our results suggest that loss-of-function mutations have occurred repeatedly within the marsupials, representing a mechanism underpinning coat colour variation.

Post-inflammatory hyperpigmentation (PIH) is a reaction process caused by an increase in melanin or abnormal melanin distribution due to inflammatory skin diseases, skin disease treatments, and external stimuli. Ultraviolet radiation can exacerbate PIH. It stimulates melanocytes, increases melanin production and deposition, and deepens the color and prolongs the duration of PIH. This study aims to investigate the inhibitory effects of Coelonin, an extract from Dendrobium officinale, on melanin production and its underlying mechanisms. Through molecular docking analysis, we found that Coelonin has significantly stronger binding capabilities to tyrosinase (TYR) and melanocortin 1 receptor (MC1R) than kojic acid, a well-known whitening agent. This stronger binding ability suggests that Coelonin may inhibit melanin production by regulating the activity of melanin metabolism-related proteins, thereby exerting its whitening effect. Compared with kojic acid, Coelonin demonstrates superior binding characteristics at the molecular level, providing stronger evidence for its potential as a whitening active ingredient. In cell experiments, Coelonin had no significant effect on the proliferation of B16-F10 melanoma cells within the concentration range of 20-40µM, but it could significantly reduce the intracellular reactive oxygen species (ROS) levels and inhibit TYR activity and melanin production. Western blot results showed that Coelonin could downregulate the expression of TYR, MITF, TRP-1, and TRP-2 proteins. In in vivo experiments, a guinea pig model of PIH was established by Ablative Fractional Resurfacing CO₂ Laser (AFR CO2) combined with UV-B irradiation. It was found that Coelonin treatment could significantly improve skin pigmentation, reduce melanin granule deposition, and did not cause skin inflammation or hyperplasia and other side effects. This study indicates that Coelonin is an efficient and safe melanin synthesis inhibitor and has the potential to be developed as a plant-derived skin whitening agent.

The aim of the study is to assess genetic variability in the population of Yakut horses of the Yana intrabreed type using an extended panel of STR loci, as well as to study the polymorphism of the ASIP, MC1R and STX17 genes that control the characteristics of hair pigmentation. The total number of animals examined was 55. Horses were tested using 25 autosomal STR loci (AHT4, AHT5, ASB2, ASB17, ASB23, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG6, HTG7, HTG10, TKY279, TKY287, TKY321, TKY343, TKY344, TKY294, TKY325, TKY333, TKY341, TKY394, VHL20) and one locus located on the X chromosome (LEX3). Analysis of the genetic structure of the Yana horse population by STR loci showed a high level of genetic variability. The total number of alleles found in 26 studied loci was 208, of which 67 alleles were rare. The average number of effective alleles was 4.69 per locus. The average values of expected (He) and observed (Ho) heterozygosity, taking into account the 25 studied autosomal loci, were 0.762 and 0.761, respectively. A study of the polymorphism of genes controlling hair pigmentation showed that the frequency of the mutant variant of the ASIP gene in the group of Yana horses was 0.500, the frequency of the mutant variant of the MC1R gene was 0.327. The dominant mutation of the STX17 gene, associated with the gray phenotype, was found in 56.36 % of the tested animals. Taking into account the results of testing for 3 genes controlling pigmentation, 14 different genotype variants were identified in the studied population.

Development of a genetically encoded melanocortin sensor for high sensitivity in vivo imaging

Genetic polymorphism significantly affects an individual’s skin health through various biological pathways such as sensitivity to ultraviolet radiation, antioxidant capacity, inflammatory response, skin barrier function, and natural aging processes. For example, the variation of MC1R gene is associated with red hair and low skin pigmentation, increasing sensitivity to UV radiation, which may accelerate the process of photoaging, such as skin sagging, wrinkles, and pigmentation. Therefore, genetic polymorphism is an important factor in the development of personalized skin health management strategies, which helps to better understand the mechanisms of skin problems and provides theoretical basis for scientific skincare. There is a close relationship between diet, skin health, and skin aging. Many basic and clinical studies have confirmed that diet is the main way for humans to obtain the nutrients needed by the body. Adjusting dietary structure and supplementing specific dietary nutrients can have the effect of delaying skin aging. For example, vitamin C is a powerful water-soluble antioxidant that is crucial for collagen biosynthesis. It can directly promote the expression of collagen genes and eliminate intracellular reactive oxygen species, prevent lipid peroxidation, and delay skin aging. Additionally, SLC23A1 gene encodes antibody transporters, participate in the balance and circulation of vitamin C in the body, and affect the level of vitamin C in the blood. Therefore, in this paper, we integrate multidimensional data including skin genetic testing data, nutrition genetic testing data, dietary and lifestyle questionnaires for data analysis, so that to provide customized nutrition and skincare solutions for each individual. It is expected that combining various omics data and offering personalized solutions will become one of the primary approaches in the field of skin care.

MC1R and IRF4 Gene Variants Are Associated with p16INK4a-Positive Epidermal Cells.

Skin pigmentation disorders involve complex biological regulation, with tyrosinase (TYR) and melanocortin 1 receptor (MC1R) serving as key therapeutic targets. Through molecular docking screening of 389 natural compounds, we identified isorhamnetin-3-O-neohespeidoside as a potent dual inhibitor, demonstrating superior binding affinities (-8.001kcal/mol for TYR and - 7.342kcal/mol for MC1R) compared to arbutin (reference compound). Subsequent in vitro validation revealed that isorhamnetin-3-O-neohespeidoside (8 µM) significantly inhibited TYR activity by 44.42% (p < 0.0001) and reduced MC1R expression by 33.39% (p < 0.0001) in B16 melanoma cells, while maintaining > 85% cell viability (IC50 = 52.22 µM). The compound also decreased melanin content by 38.7% (p < 0.0001) and upregulated LC3-II expression (2.1-fold vs. control, p < 0.0001), indicating enhanced autophagy. These results demonstrate that isorhamnetin-3-O-neohespeidoside, a flavonoid glycoside from Typhae Pollen, acts through multiple mechanisms - direct enzyme inhibition, receptor downregulation, and autophagy induction - making it a promising natural candidate for hyperpigmentation treatment. Our integrated approach combining computational screening with experimental validation provides a robust framework for identifying multi-target depigmenting agents.

Genetic polymorphisms in Agouti signaling protein (ASIP) and melanocortin 1 receptor (MC1R) genes and their association with coat color in native Bulgarian sheep breeds.

Ultraviolet (UV) radiation accelerates skin damage and photoageing, leading to visible signs such as wrinkles, loss of elasticity and uneven pigmentation. UV radiation causes direct DNA damage, primarily through the formation of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs), which can lead to mutations and cellular dysfunction if not repaired. While natural defence mechanisms like melanin production and DNA repair pathways mitigate this damage, prolonged or excessive UV exposure can overwhelm these defences, resulting in cumulative skin damage. The melanocortin 1 receptor (MC1R) plays a key role in melanogenesis and also appears to play a role in DNA repair. Salt-inducible kinases (SIKs), critical enzymes in the MC1R pathway, are known to influence melanin production, but their role in DNA repair and photodamage remains unclear. This study investigated the role of SIK in DNA repair and photodamage, focusing on two novel cosmetic ingredients, SIK inhibitors, coded SLT-008 and SLT-001. The inhibitory effects of the ingredients on SIK activity were measured using biochemical and cellular assays. Their safety profiles were evaluated through invitro studies and clinical trials. To analyse their impact on UV-B-induced DNA damage and repair, both inhibitors were topically applied to skin extracts in an exvivo model. Finally, clinical studies were conducted in healthy volunteers irradiated with UV-R. Efficacy was determined by measuring CPD levels, matrix metalloproteinase-1 (MMP-1), expression and erythema formation following UV exposure. Both ingredients effectively inhibited SIK activity and demonstrated good safety profiles. Exvivo experiments revealed that immediate post-UV-B application of both ingredients significantly reduced UV-B-induced DNA damage, as shown by decreased CPDs, and promoted tissue repair. Additionally, both inhibitors suppressed MMP-1 expression, an enzyme that plays a key role in the breakdown of collagen, thereby accelerating photoageing. These findings were confirmed in the clinical study, which demonstrated that topically applied SLT-001 enhanced DNA repair, reduced MMP-1 expression and decreased erythema formation. Here we described the comprehensive role of SIK inhibition in DNA and dermal repair. This highlights its crucial role in protecting skin against UV-induced photodamage and offering broad protection against actinic ageing.