A Novel Role for Mc1r in the Parallel Evolution of Depigmentation in Independent Populations of the Cavefish Astyanax mexicanus

The evolution of degenerate characteristics remains a poorly understood phenomenon. Only recently has the identification of mutations underlying regressive phenotypes become accessible through the use of genetic analyses. Focusing on the Mexican cave tetra Astyanax mexicanus, we describe, here, an analysis of the brown mutation, which was first described in the literature nearly 40 years ago. This phenotype causes reduced melanin content, decreased melanophore number, and brownish eyes in convergent cave forms of A. mexicanus. Crosses demonstrate non-complementation of the brown phenotype in F2 individuals derived from two independent cave populations: Pachón and the linked Yerbaniz and Japonés caves, indicating the same locus is responsible for reduced pigmentation in these fish. While the brown mutant phenotype arose prior to the fixation of albinism in Pachón cave individuals, it is unclear whether the brown mutation arose before or after the fixation of albinism in the linked Yerbaniz/Japonés caves. Using a QTL approach combined with sequence and functional analyses, we have discovered that two distinct genetic alterations in the coding sequence of the gene Mc1r cause reduced pigmentation associated with the brown mutant phenotype in these caves. Our analysis identifies a novel role for Mc1r in the evolution of degenerative phenotypes in blind Mexican cavefish. Further, the brown phenotype has arisen independently in geographically separate caves, mediated through different mutations of the same gene. This example of parallelism indicates that certain genes are frequent targets of mutation in the repeated evolution of regressive phenotypes in cave-adapted species

Antioxidant Machinery Differs between Melanic and Light Nestlings of Two Polymorphic Raptors

Colour polymorphism results from the expression of multiallelic genes generating phenotypes with very distinctive colourations. Most colour polymorphisms are due to differences in the type or amount of melanins present in each morph, which also differ in several behavioural, morphometric and physiological attributes. Melanin-based colour morphs could also differ in the levels of glutathione (GSH), a key intracellular antioxidant, because of the role of this molecule in melanogenesis. As GSH inhibits the synthesis of eumelanin (i.e. the darkest melanin form), individuals of darker morphs are expected to have lower GSH levels than those of lighter morphs. We tested this prediction in nestlings of two polymorphic raptors, the booted eagle Hieraaetus pennatus and the Eleonora's falcon Falco eleonorae, both of which occur in two morphs differing in the extent of eumelanic plumage. As expected, melanic booted eagle nestlings had lower blood GSH levels than light morph eagle nestlings. In the Eleonora's falcon, however, melanic nestlings only had lower GSH levels after controlling for the levels of other antioxidants. We also found that melanic female eagle nestlings had higher levels of antioxidants other than GSH and were in better body condition than light female eagle nestlings. These findings suggest an adaptive response of melanic nestlings to compensate for reduced GSH levels. Nevertheless, these associations were not found in falcons, indicating species-specific particularities in antioxidant machinery. Our results are consistent with previous work revealing the importance of GSH on the expression of melanic characters that show continuous variation, and suggest that this pathway also applies to discrete colour morphs. We suggest that the need to maintain low GSH levels for eumelanogenesis in dark morph individuals may represent a physiological constraint that helps regulate the evolution and maintenance of polymorphisms

Melanism in Peromyscus Is Caused by Independent Mutations in Agouti

Identifying the molecular basis of phenotypes that have evolved independently can provide insight into the ways genetic and developmental constraints influence the maintenance of phenotypic diversity. Melanic (darkly pigmented) phenotypes in mammals provide a potent system in which to study the genetic basis of naturally occurring mutant phenotypes because melanism occurs in many mammals, and the mammalian pigmentation pathway is well understood. Spontaneous alleles of a few key pigmentation loci are known to cause melanism in domestic or laboratory populations of mammals, but in natural populations, mutations at one gene, the melanocortin-1 receptor (Mc1r), have been implicated in the vast majority of cases, possibly due to its minimal pleiotropic effects. To investigate whether mutations in this or other genes cause melanism in the wild, we investigated the genetic basis of melanism in the rodent genus Peromyscus, in which melanic mice have been reported in several populations. We focused on two genes known to cause melanism in other taxa, Mc1r and its antagonist, the agouti signaling protein (Agouti). While variation in the Mc1r coding region does not correlate with melanism in any population, in a New Hampshire population, we find that a 125-kb deletion, which includes the upstream regulatory region and exons 1 and 2 of Agouti, results in a loss of Agouti expression and is perfectly associated with melanic color. In a second population from Alaska, we find that a premature stop codon in exon 3 of Agouti is associated with a similar melanic phenotype. These results show that melanism has evolved independently in these populations through mutations in the same gene, and suggest that melanism produced by mutations in genes other than Mc1r may be more common than previously thought

Estado nutricional pré-gestacional, ganho de peso materno, condições da assistência pré-natal e desfechos perinatais adversos entre puérperas adolescentes Pre-pregnancy nutritional status, maternal weight gain, prenatal care, and adverse perinatal outcomes among adolescent mothers

OBJETIVO: Identificar associação entre estado nutricional pré-gestacional, ganho ponderal materno e condições do pré-natal com os desfechos prematuridade e baixo peso ao nascer (BPN) em filhos de mães adolescentes. MÉTODOS: Estudo transversal com 542 pares de puérperas adolescentes e conceptos atendidos em uma maternidade pública do município do Rio de Janeiro (RJ). Os dados foram coletados em prontuários. Para verificar a associação entre as variáveis independentes e os desfechos estudados, foram estimados a odds ratio (OR) e o intervalo de confiança (IC) de 95%. RESULTADOS: Quanto ao estado nutricional pré-gestacional das adolescentes, 87% apresentavam eutrofia, 1% baixo peso, 10% sobrepeso e 2% obesidade. A inadequação do ganho de peso gestacional total (72%) superou a adequação (28%). O peso ao nascer foi favorecido com maior ganho de peso gestacional e reduzido com início tardio do pré-natal (PN). A comparação entre os grupos de conceptos com baixo peso e com peso adequado ao nascer revelou diferenças significativas entre as médias das variáveis: intervalo entre a última gestação e a atual (p = 0,022); peso pré-gestacional (p = 0,018); índice de massa corporal pré-gestacional (p < 0,001) e ganho de peso gestacional total (p = 0,047). As chances de BPN (OR 2,70; IC 95% 1,45 - 5,06) e de prematuridade (OR 5,82; IC 95% 3,10 - 10,92) reduziram quando a adolescente recebeu 6 ou mais consultas de PN. CONCLUSÃO: O peso ao nascer foi relacionado ao intervalo intergestacional, ao peso pré-gestacional e ao índice de massa corporal pré-gestacional. A frequência mínima de 6 consultas de assistência pré-natal constituiu-se em fator de proteção contra o BPN e a prematuridade.<br>OBJECTIVE: To identify the association between pre-gestational nutritional status, maternal weight gain, and prenatal care with low birth weight (LBW) and prematurity outcomes in infants of adolescent mothers. METHODS: Cross-sectional study with 542 pairs of adolescent mothers and their children attending a public maternity hospital in Rio de Janeiro. Data were collected from medical records. To determine the association between independent variables and the outcomes studied, odds ratio (OR) and a 95% confidence interval (CI) were estimated RESULTS: With respect to pre-pregnancy nutritional status of adolescents, 87% had normal weight, 1% were underweight, 10% were overweight, and 2% obese. Inadequate total gestational weight gain (72%) exceeded adequacy (28%). Birth weight was favored with greater gestational weight gain, and reduced with late onset of prenatal care. The comparison between the low birth weight and normal birth weight groups revealed significant differences between variable means: interval between the past pregnancy and current pregnancy (p = 0.022), pre-gestational weight (p = 0.018); pre-gestational body mass index (p < 0.001), and total gestational weight gain (p = 0.047). The odds of LBW (OR 2.70, 95% CI 1.45 to 5.06) and prematurity (OR 5.82, 95% CI 3.10 to 10.92) fell when the adolescent received six or more prenatal visits. CONCLUSION: Birth weight was associated with inter-gestational interval, pre-pregnancy weight and body mass index before pregnancy. The minimum frequency of six prenatal care visits was a protective factor against LBW and prematurity