Pigmentation Phenotypes Research Articles

Cutaneous pharmacologic cAMP induction induces melanization of the skin and improves recovery from ultraviolet injury in melanocortin 1 receptor-intact or heterozygous skin.

Homozygous loss of function of the melanocortin 1 receptor (MC1R) is associated with a pheomelanotic pigment phenotype and increased melanoma risk. MC1R heterozygosity is less well studied, although individuals inheriting one loss-of-function MC1R allele are also melanoma-prone. Using the K14-Scf C57BL/6J animal model whose skin is characterized by lifelong retention of interfollicular epidermal melanocytes like that of the human, we studied pigmentary, UV responses, and DNA repair capacity in the skin of variant Mc1r background. Topical application of forskolin, a skin-permeable pharmacologic activator of cAMP induction to mimic native Mc1r signaling, increased epidermal eumelanin levels, increased the capacity of Mc1r-heterozygous skin to resist UV-mediated inflammation, and enhanced the skin's ability to clear UV photolesions from DNA. Interestingly, topical cAMP induction also promoted melanin accumulation, UV resistance, and accelerated clearance in Mc1r fully intact skin. Together, our findings suggest that heterozygous Mc1r loss is associated with an intermediately melanized and DNA repair-proficient epidermal phenotype and that topical cAMP induction enhances UV resistance in Mc1r-heterozygous or Mc1r-wild-type individuals by increasing eumelanin deposition and by improving nucleotide excision repair.

MEK inhibition remodels the active chromatin landscape and induces SOX10 genomic recruitment in BRAF(V600E) mutant melanoma cells

BackgroundThe MAPK/ERK signaling pathway is an essential regulator of numerous cell processes that are crucial for normal development as well as cancer progression. While much is known regarding MAPK/ERK signal conveyance from the cell membrane to the nucleus, the transcriptional and epigenetic mechanisms that govern gene expression downstream of MAPK signaling are not fully elucidated.ResultsThis study employed an integrated epigenome analysis approach to interrogate the effects of MAPK/ERK pathway inhibition on the global transcriptome, the active chromatin landscape, and protein–DNA interactions in 501mel melanoma cells. Treatment of these cells with the small-molecule MEK inhibitor AZD6244 induces hyperpigmentation, widespread gene expression changes including alteration of genes linked to pigmentation, and extensive epigenomic reprogramming of transcriptionally distinct regulatory regions associated with the active chromatin mark H3K27ac. Regulatory regions with differentially acetylated H3K27ac regions following AZD6244 treatment are enriched in transcription factor binding motifs of ETV/ETS and ATF family members as well as the lineage-determining factors MITF and SOX10. H3K27ac-dense enhancer clusters known as super-enhancers show similar transcription factor motif enrichment, and furthermore, these super-enhancers are associated with genes encoding MITF, SOX10, and ETV/ETS proteins. Along with genome-wide resetting of the active enhancer landscape, MEK inhibition also results in widespread SOX10 recruitment throughout the genome, including increased SOX10 binding density at H3K27ac-marked enhancers. Importantly, these MEK inhibitor-responsive enhancers marked by H3K27ac and occupied by SOX10 are located near melanocyte lineage-specific and pigmentation genes and overlap numerous human SNPs associated with pigmentation and melanoma phenotypes, highlighting the variants located within these regions for prioritization in future studies.ConclusionsThese results reveal the epigenetic reprogramming underlying the re-activation of melanocyte pigmentation and developmental transcriptional programs in 501mel cells in response to MEK inhibition and suggest extensive involvement of a MEK-SOX10 axis in the regulation of these processes. The dynamic chromatin changes identified here provide a rich genomic resource for further analyses of the molecular mechanisms governing the MAPK pathway in pigmentation- and melanocyte-associated diseases.

Exposure to a competitive social environment activates an epigenetic mechanism that limits pheomelanin synthesis in zebra finches.

Competitive environments promote high testosterone levels, produce oxidative stress and, consequently, impair cellular homeostasis. The regulation of genes involved in the synthesis of the pigment pheomelanin in melanocytes seems to help to maintain homeostasis against environmental oxidative stress. Here, we experimentally increased social interactions in some zebra finch (Taeniopygia guttata) males by keeping them in groups of six birds during feather growth, while others were kept alone, to test if melanocytes show epigenetic lability under a competitive social environment. As these changes may depend on the oxidative status, we administrated buthionine sulfoximine (BSO) to decrease the antioxidant capacity of some birds. The competitive environment downregulated a gene involved in pheomelanin synthesis (Slc7a11) by changing the level of DNA methylation in feather melanocytes. In other genes involved in pheomelanin synthesis (Slc45a2, MC1R and AGRP), DNA methylation was also affected, but no changes in expression were detected. Exposure to the competitive environment did not affect systemic oxidative stress and damage, indicating that a protective epigenetic mechanism that changes the expression of Slc7a11 may have been activated. However, no changes to the pigmentation phenotype of birds were found, probably due to the short duration or low intensity of the competitive environment. BSO treatment did not affect the epigenetic mechanism, suggesting that the antioxidant capacity of birds was high enough to deal with the competitive environment. An epigenetic mechanism limiting pheomelanin synthesis therefore becomes activated under exposure to a competitive environment in male zebra finches, which may help to avoid damage caused by competitive interactions.

Assessment of Predictors of Sun Sensitivity as Defined by Fitzpatrick Skin Phototype in an Ecuadorian Population and Its Correlation with Skin Damage

Background: The Fitzpatrick skin phototype scale (FSPTS) is a widely used instrument to assess skin type. Methods: A cross-sectional survey collected responses from 254 subjects from Quito regarding self-reported FSPTS, gender, age, education, and tobacco and alcohol consumption. Univariate and multivariate logistic regression analyses were performed to determine if ethnicity, hair color, and eye color significantly predict FSPTS. In addition, we studied the correlation between FSPTS and the SCINEXA scale with Pearson’s correlation coefficient. Results: Ethnicity, eye color, and hair color are significant independent predictors of FSPTS (p < 0.0001). Conclusions: Patient self-reported race and pigmentary phenotypes are inaccurate predictors of sun sensitivity as defined by Fitzpatrick skin phototype. Our study does not fully represent the population of the country. There are limitations to using patient-reported race and appearance in predicting individual sunburn risk.

Associations of pigmentary and naevus phenotype with melanoma risk in two populations with comparable ancestry but contrasting levels of ambient sun exposure.

BackgroundPeople at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes.ObjectiveWe examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population‐based, case–control studies with comparable ancestry but different ambient sun exposure.MethodsData were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case–control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders.ResultsHair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self‐reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk.ConclusionsClassifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self‐reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development.

Dissecting the genetic control of root and leaf tissue-specific anthocyanin pigmentation in carrot (Daucus carota L.).

Inheritance, QTL mapping, phylogenetic, and transcriptome (RNA-Seq) analyses provide insight into the genetic control underlying carrot root and leaf tissue-specific anthocyanin pigmentation and identify candidate genes for root phloem pigmentation. Purple carrots can accumulate large quantities of anthocyanins in their root tissues, as well as in other plant parts. This work investigated the genetic control underlying tissue-specific anthocyanin pigmentation in the carrot root phloem and xylem, and in leaf petioles. Inheritance of anthocyanin pigmentation in these three tissues was first studied in segregating F2 and F4 populations, followed by QTL mapping of phloem and xylem anthocyanin pigments (independently) onto two genotyping by sequencing-based linkage maps, to reveal two regions in chromosome 3, namely P1 and P3, controlling pigmentation in these three tissues. Both P1 and P3 condition pigmentation in the phloem, with P3 also conditioning pigmentation in the xylem and petioles. By means of linkage mapping, phylogenetic analysis, and comparative transcriptome (RNA-Seq) analysis among carrot roots with differing purple pigmentation phenotypes, we identified candidate genes conditioning pigmentation in the phloem, the main tissue influencing total anthocyanin levels in the root. Among them, a MYB transcription factor, DcMYB7, and two cytochrome CYP450 genes with putative flavone synthase activity were identified as candidates regulating both the presence/absence of pigmentation and the concentration of anthocyanins in the root phloem. Concomitant expression patterns of DcMYB7 and eight anthocyanin structural genes were found, suggesting that DcMYB7 regulates transcription levels in the latter. Another MYB, DcMYB6, was upregulated in specific purple-rooted samples, suggesting a genotype-specific regulatory activity for this gene. These data contribute to the understanding of anthocyanin regulation in the carrot root at a tissue-specific level and maybe instrumental for improving carrot nutritional value.

Computational Modeling of Anthocyanin Pathway Evolution: Biases, Hotspots, and Trade-offs

The alteration of metabolic pathways is a common mechanism underlying the evolution of new phenotypes. Flower color is a striking example of the importance of metabolic evolution in a complex phenotype, wherein shifts in the activity of the underlying pathway lead to a wide range of pigments. Although experimental work has identified common classes of mutations responsible for transitions among colors, we lack a unifying model that relates pathway function and activity to the evolution of distinct pigment phenotypes. One challenge in creating such a model is the branching structure of pigment pathways, which may lead to evolutionary trade-offs due to competition for shared substrates. In order to predict the effects of shifts in enzyme function and activity on pigment production, we created a simple kinetic model of a major plant pigmentation pathway: the anthocyanin pathway. This model describes the production of the three classes of blue, purple, and red anthocyanin pigments, and accordingly, includes multiple branches and substrate competition. We first studied the general behavior of this model using a naïve set of parameters. We then stochastically evolved the pathway toward a defined optimum and analyzed the patterns of fixed mutations. This approach allowed us to quantify the probability density of trajectories through pathway state space and identify the types and number of changes. Finally, we examined whether our simulated results qualitatively align with experimental observations, i.e., the predominance of mutations which change color by altering the function of branching genes in the pathway. These analyses provide a theoretical framework that can be used to predict the consequences of new mutations in terms of both pigment phenotypes and pleiotropic effects.

Dyspigmented hypertrophic scars: Beyond skin color.

Although pigment synthesis is well understood, relevant mechanisms of psychologically debilitating dyspigmentation in nascent tissue after cutaneous injuries are still unknown. Here, differences in genomic transcription of hyper- and hypopigmented tissue relative to uninjured skin were investigated using a red Duroc swine scar model. Transcription profiles differed based on pigmentation phenotypes with a trend of more upregulation or downregulation in hyper- or hypopigmented scars, respectively. Ingenuity Pathway Analysis of significantly modulated genes in both pigmentation phenotypes showed pathways related to redox, metabolic, and inflammatory responses were more present in hypopigmented samples, while those related to stem cell development differentiation were found mainly in hyperpigmented samples. Cell-cell and cell-extracellular matrix interactions and inflammation responses were predicted (z-score) active in hyperpigmented and inactive in hypopigmented. The proinflammatory high-mobility group box 1 pathway showed the opposite trend. Analysis of differentially regulated mutually exclusive genes showed an extensive presence of metabolic, proinflammatory, and oxidative stress pathways in hypopigmented scars, while melanin synthesis, glycosaminoglycans biosynthesis, and cell differentiation pathways were predominant in hyperpigmented scar. Several potential therapeutic gene targets have been identified.

Countershading in zebrafish results from an Asip1 controlled dorsoventral gradient of pigment cell differentiation

Dorso-ventral (DV) countershading is a highly-conserved pigmentary adaptation in vertebrates. In mammals, spatially regulated expression of agouti-signaling protein (ASIP) generates the difference in shading by driving a switch between the production of chemically-distinct melanins in melanocytes in dorsal and ventral regions. In contrast, fish countershading seemed to result from a patterned DV distribution of differently-coloured cell-types (chromatophores). Despite the cellular differences in the basis for counter-shading, previous observations suggested that Agouti signaling likely played a role in this patterning process in fish. To test the hypotheses that Agouti regulated counter-shading in fish, and that this depended upon spatial regulation of the numbers of each chromatophore type, we engineered asip1 homozygous knockout mutant zebrafish. We show that loss-of-function asip1 mutants lose DV countershading, and that this results from changed numbers of multiple pigment cell-types in the skin and on scales. Our findings identify asip1 as key in the establishment of DV countershading in fish, but show that the cellular mechanism for translating a conserved signaling gradient into a conserved pigmentary phenotype has been radically altered in the course of evolution.

Meta-analysis and prioritization of human skin pigmentation-associated GWAS-SNPs using ENCODE data-based web-tools.

Skin pigmentation in human is a complex trait, which varies widely, both within and between human populations. The exact players governing the trait of skin pigmentation remain elusive till date. Various Genome Wide Association Studies (GWAS) have shown the association of different genomic variants with normal human skin pigmentation, often indicating genes with no direct implications in melanin biosynthesis or distribution. Little has been explained in terms of the functionality of the associated Single-Nucleotide Polymorphisms (SNPs) with respect to modulating the skin pigmentation phenotype. In the present study, which, to our knowledge, is the first of its kind, we tried to analyze and prioritize 519 non-coding SNPs and 24 3'UTR SNPs emerging from 14 different human skin pigmentation-related GWAS, primarily using several ENCODE-based web-tools like rSNPBase, RegulomeDB, HaploReg, etc., most of which incorporate experimentally validated evidences in their predictions. Using this comprehensive, in-silico, analytical approach, we successfully prioritized all the pigmentation-associated GWAS-SNPs and tried to annotate pigmentation-related functionality to them, which would pave the way for deeper understanding of the molecular basis of human skin pigmentation variations.

Long-term experimental hybridisation results in the evolution of a new sex chromosome in swordtail fish

The remarkable diversity of sex determination mechanisms known in fish may be fuelled by exceptionally high rates of sex chromosome turnovers or transitions. However, the evolutionary causes and genomic mechanisms underlying this variation and instability are yet to be understood. Here we report on an over 30-year evolutionary experiment in which we tested the genomic consequences of hybridisation and selection between two Xiphophorus fish species with different sex chromosome systems. We find that introgression and imposing selection for pigmentation phenotypes results in the retention of an unexpectedly large maternally derived genomic region. During the hybridisation process, the sex-determining region of the X chromosome from one parental species was translocated to an autosome in the hybrids leading to the evolution of a new sex chromosome. Our results highlight the complexity of factors contributing to patterns observed in hybrid genomes, and we experimentally demonstrate that hybridisation can catalyze rapid evolution of a new sex chromosome.

A curated gene list for expanding the horizons of pigmentation biology.

Over the past century, studies of human pigmentary disorders along with mouse and zebrafish models have shed light on the many cellular functions associated with visible pigment phenotypes. This has led to numerous genes annotated with the ontology term "pigmentation" in independent human, mouse, and zebrafish databases. Comparisons among these datasets revealed that each is individually incomplete in documenting all genes involved in integument-based pigmentation phenotypes. Additionally, each database contained inherent species-specific biases in data annotation, and the term "pigmentation" did not solely reflect integument pigmentation phenotypes. This review presents a comprehensive, cross-species list of 650 genes involved in pigmentation phenotypes that was compiled with extensive manual curation of genes annotated in OMIM, MGI, ZFIN, and GO. The resulting cross-species list of genes both intrinsic and extrinsic to integument pigment cells provides a valuable tool that can be used to expand our knowledge of complex, pigmentation-associated pathways.

A recent shift in the pigmentation phenotype of a wild Neotropical primate

The colors of primates are among the most diverse phenotypes in mammals. These colors are mostly produced by the deposition of melanin pigments in hairs. Many species show considerable variability in pigmentation, but this is always temporarily fixed. Here we report the first rapid change in the pigmentation phenotype of a primate. In the last five years, the pelage of mantled howler monkeys Alouatta palliata inhabiting Costa Rica has started to change from fully black to yellowish, constituting a conspicuous color change. Raman spectroscopy analyses of hairs show that the change is due to a shift toward the production of the sulphurated form of melanin, termed pheomelanin. Most animals with anomalous coloration have been observed in forests surrounding intensive cultivations where sulfur-containing pesticides are frequently used. Exposure to environmental sulfur may increase the availability of sulfhydryls to cells, which may favor pheomelanin synthesis in melanocytes and explain the pigmentation shift.

Predation risk determines pigmentation phenotype in nuthatches by melanin-related gene expression effects.

Pigments determine the appearance of organisms. However, pigment production can be associated with physiological constraints as in the case of pheomelanin, the sulphurated form of melanin whose synthesis in melanocytes consumes cysteine and consequently reduces the availability of glutathione (GSH) to exert antioxidant protection. Pheomelanogenesis may thus increase the susceptibility to suffer chronic oxidative stress. I investigated the possibility that environmental lability in the expression of genes regulating pheomelanogenesis protects from oxidative stress, a situation in which GSH is most required. By broadcasting adult alarm calls, I manipulated the perception of predation risk, a natural source of oxidative stress, in free-living Eurasian nuthatch Sitta europaea nestlings developing pheomelanin-pigmented flank feathers. The manipulation affected the consumption of GSH that resulted from the expression of two genes (Slc7a11 and Slc45a2) influencing cysteine/GSH availability in cells, as these genes were down-regulated in the feather melanocytes of the nestlings with lowest intracellular antioxidant capacity (i.e. lowest GSH levels). Systemic oxidative damage increased with Slc7a11 expression in feather melanocytes, suggesting that the observed down-regulation was physiologically advantageous. The nestlings exposed to an increased perception of predation risk developed flank feathers of reduced colour intensity. These results indicate that perceived predation risk can determine the pigmentation phenotype by (probably epigenetic) effects on gene expression that protect from physiological constraints imposed by pheomelanin production.

Association of multiple primary melanomas with malignancy risk: A population-based analysis of entries from the Surveillance, Epidemiology, and End Results program database during 1973-2014

Genetic and environmental risk factors have been associated with the development of multiple primary melanomas (MPMs). We hypothesized that individuals with MPMs might have an increased incidence of internal malignancies. To identify the risk for subsequent malignancies in MPM patients. Multiple primary standardized incidence ratios were analyzed for individuals with ≥1, ≥2 and≥3 primary melanomas (PMs) recorded in the Surveillance, Epidemiology, and End Results database during 1973-2014. We identified 223,799 individuals with ≥1 PM, 19,709 with ≥2 PMs, and 3,995 with ≥3 PMs. Risks of subsequent internal malignancy increased with number of PMs, with observed:expected ratios of 0.99, 1.14, and 1.23 (P<.05) for patients with ≥1 PM, ≥2 PMs, and ≥3 PMs, respectively. Internal malignancy was higher in younger MPM patients and those with superficial spreading melanoma. The most common malignancies among MPM patients included breast, prostate, thyroid, soft tissue, brain, kidney, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. Risk for subsequentcutaneous melanoma increased with observed:expected ratios of 8.09, 22.52, 41.03 (P<.05) for patients with ≥1 PM, ≥2 PMs, and ≥3 PMs, respectively. Surveillance, Epidemiology, and End Results records limited information about pigmentation phenotypes, histology, and treatments. Patients with MPMs have an increased risk for subsequent internal and cutaneous malignancies and might benefit from tight adherence to age-specific cancer screening.

Rhodobacterales use a unique L-threonine kinase for the assembly of the nucleotide loop of coenzyme B12.

Several of the enzymes involved in the conversion of adenosylcobyric acid (AdoCby) to adenosylcobamide (AdoCba) are yet to be identified and characterized in some cobamide (Cba)-producing prokaryotes. Using a bioinformatics approach, we identified the bluE gene (locus tag RSP_0788) of Rhodobacter sphaeroides 2.4.1 as a putative functional homolog of the L-threonine kinase enzyme (PduX, EC 2.7.1.177) of S. enterica. In AdoCba, (R)-1-aminopropan-2-ol O-phosphate (AP-P) links the nucleotide loop to the corrin ring; most known AdoCba producers derive AP-P from L-Thr-O-3-phosphate (L-Thr-P). Here, we show that RsBluE has L-Thr-independent ATPase activity in vivo and in vitro. We used 31 P-NMR spectroscopy to show that RsBluE generates L-Thr-P at the expense of ATP and is unable to use L-Ser as a substrate. BluE from R. sphaeroides or Rhodobacter capsulatus restored AdoCba biosynthesis in S. enterica ΕpduX and R. sphaeroides ΕbluE mutant strains. R. sphaeroides ΕbluE strains exhibited a decreased pigment phenotype that was restored by complementation with BluE. Finally, phylogenetic analyses revealed that bluE was restricted to the genomes of a few Rhodobacterales that appear to have a preference for a specific form of Cba, namely Coᴽ-(ᴽ-5,6-dimethylbenzimidazolyl-Coᵦ-adenosylcobamide (a.k.a. adenosylcobalamin, AdoCbl; coenzyme B12 , CoB12 ).

Maternal Genetic Effects in Astyanax Cavefish Development

The role of maternal factors in the evolution of development is poorly understood. Here we describe the use of reciprocal hybridization between the surface dwelling (surface fish, SF) and cave dwelling (cavefish, CF) morphs of the teleost Astyanax mexicanus to determine investigate the roles of maternal genetic effects in cavefish development. Reciprocal hybridization, a procedure in which F1 hybrids are generated by fertilizing SF eggs with CF sperm (SF X CF hybrids) and CF eggs with SF sperm (CF X SF hybrids), revealed that the CF degenerative eye phenotype showed maternal genetic effects. The eyes of CF X SF hybrids resembled the degenerate eyes of CF in showing ventral reduction of the retina and corresponding displacement of the lens within the optic cup, a smaller lens and eyeball, more lens apoptosis, a smaller cartilaginous sclera, and lens-specific gene expression characteristics compared to SF X CF hybrids, which showed eye and lens gene expression phenotypes resembling SF. In contrast, reciprocal hybridization failed to support any roles for maternal genetic effects in the CF regressive pigmentation phenotype or in CF constructive changes related to enhanced jaw development. The Astyanax orthologs of mMaternal transcripts encoded by some of thethe pou2f1b, runx2b, and axin1 genes, which are key involved in determining ventral embryonic fates, genes involved in zebrafish dorsoventral patterning were increased in unfertilized CF eggs. In contrast, maternal mRNAs encoded by the ß-catenin and syntabulin genes, which control dorsal embryonic fates, were unchangedwith theshowed similar expression levels in unfertilized SF and CF eggs. This study reveals that CF eye degeneration is controlled by changes in maternal factors produced during oogenesis and introduces A. mexicanus as a model system for studying the role of maternal changes in the evolution of development.

New Insights into the Melanophilin (MLPH) Gene Affecting Coat Color Dilution in Rabbits.

Coat color dilution corresponds to a specific pigmentation phenotype that leads to a dilution of wild type pigments. It affects both eumelanin and pheomelanin containing melanosomes. The mode of inheritance of the dilution phenotype is autosomal recessive. Candidate gene approaches focused on the melanophilin (MLPH) gene highlighted two variants associated with the dilution phenotype in rabbits: The c.111-5C>A variant that is located in an acceptor splice site or the c.585delG variant, a frameshift mutation. On the transcript level, the skipping of two exons has been reported as the molecular mechanism responsible for the coat color dilution. To clarify, which of the two variants represents the causal variant, (i) we analyzed their allelic segregation by genotyping Castor and Chinchilla populations, and (ii) we evaluated their functional effects on the stability of MLPH transcripts in skin samples of animals with diluted or wild type coat color. Firstly, we showed that the c.585delG variant showed perfect association with the dilution phenotype in contrast to the intronic c.111-5C>A variant. Secondly, we identified three different MLPH isoforms including the wild type isoform, the exon-skipping isoform and a retained intron isoform. Thirdly, we observed a drastic and significant decrease of MLPH transcript levels in rabbits with a coat color dilution (p-values ranging from 10−03 to 10−06). Together, our results bring new insights into the coat color dilution trait.

Solar and terrestrial radiations explain continental-scale variation in bird pigmentation.

Animals living on the earth's surface are protected from the damaging effects of solar ultraviolet (UV) radiation by melanin pigments that color their integument. UV levels that reach the earth's surface vary spatially, but the role of UV exposure in shaping clinal variations in animal pigmentation has never been tested. Here, we show at a continental scale in Europe that golden eagles Aquila chrysaetos reared in territories with a high solar UV-B radiation exposure deposit lower amounts of the sulphurated form of melanin (pheomelanin) in feathers and consequently develop darker plumage phenotypes than eagles from territories with lower radiation exposure. This clinal variation in pigmentation is also explained by terrestrial γ radiation levels in the rearing territories by a similar effect on the pheomelanin content of feathers, unveiling natural radioactivity as a previously unsuspected factor shaping animal pigmentation. These findings show for the first time the potential of solar and terrestrial radiations to explain pigmentation phenotype diversity in animals, including humans, at large spatial scales.

Maternal genetic effects in Astyanax cavefish development

The role of maternal factors in the evolution of development is poorly understood. Here we describe the use of reciprocal hybridization between the surface dwelling (surface fish, SF) and cave dwelling (cavefish, CF) morphs of the teleost Astyanax mexicanus to investigate the roles of maternal genetic effects in cavefish development. Reciprocal hybridization, a procedure in which F1 hybrids are generated by fertilizing SF eggs with CF sperm (SF × CF hybrids) and CF eggs with SF sperm (CF × SF hybrids), revealed that the CF degenerative eye phenotype showed maternal genetic effects. The eyes of CF × SF hybrids resembled the degenerate eyes of CF in showing ventral reduction of the retina and corresponding displacement of the lens within the optic cup, a smaller lens and eyeball, more lens apoptosis, a smaller cartilaginous sclera, and lens-specific gene expression characteristics compared to SF × CF hybrids, which showed eye and lens gene expression phenotypes resembling SF. In contrast, reciprocal hybridization failed to support roles for maternal genetic effects in the CF regressive pigmentation phenotype or in CF constructive changes related to enhanced jaw development. Maternal transcripts encoded by the pou2f1b, runx2b, and axin1 genes, which are involved in determining ventral embryonic fates, were increased in unfertilized CF eggs. In contrast, maternal mRNAs encoded by the ß-catenin and syntabulin genes, which control dorsal embryonic fates, showed similar expression levels in unfertilized SF and CF eggs. Furthermore, maternal transcripts of a sonic hedgehog gene were detected in SF and CF eggs and early cleaving embryos. This study reveals that CF eye degeneration is controlled by changes in maternal factors produced during oogenesis and introduces A. mexicanus as a model system for studying the role of maternal changes in the evolution of development.