Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard (Podarcis muralis), which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions near genes associated with pterin [sepiapterin reductase(SPR)] and carotenoid [beta-carotene oxygenase 2(BCO2)] metabolism, demonstrating that a core gene in the housekeeping pathway of pterin biosynthesis has been coopted for bright coloration in reptiles and indicating that these loci exert pleiotropic effects on other aspects of physiology. Pigmentation differences are explained by extremely divergent alleles, and haplotype analysis revealed abundant transspecific allele sharing with other lacertids exhibiting color polymorphisms. The evolution of these conspicuous color ornaments is the result of ancient genetic variation and cross-species hybridization.

Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors.These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard, which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions, near genes associated with pterin (SPR) and carotenoid metabolism (BCO2), demonstrating that a core gene in the housekeeping pathway of pterin biosynthesis has been co-opted for bright coloration in reptiles and indicating that these loci exert pleiotropic effects on other aspects of physiology. Pigmentation differences are explained by extremely divergent alleles and haplotype analysis revealed abundant trans-specific allele sharing with other lacertids exhibiting color polymorphisms. The evolution of these conspicuous color ornaments is the result of ancient genetic variation and cross-species hybridization.To investigate the genetic and evolutionary bases of the vivid colors displayed by reptiles, and to test hypothesis about how and why color polymorphisms and correlated trait variation persist within populations, we studied the European common wall lizard (Podarcis muralis) (Fig. 1A)a polymorphic lizard in which the ventral scales of males and females exhibits one of three distinct colors (orange, yellow, and white) or a mosaic pattern combining two colors (orange-yellow and orange-white) (12,13). Each of these five color morphs can be found throughout most of the broad geographic distribution of the species (Fig. 1B), and are shared by intraspecific sub-lineages thought to have diverged up to 2.5 million years ago (14). While the white morph is typically the most common (>50%), the relative frequency of morphs is highly variable even at small regional scales and the yellow or orange morphs may occasionally prevail (15,16) (SI Appendix, Fig. S1). The widespread distribution and persistence of color variation is thought to be due to balancing selection and the product of an interplay between natural and sexual selection (17). Previous work has shown that morphs mate assortatively with respect to ventral color (~75% of pairs) and differ in additional traits, including morphology, behavior, physiology, immunology, and reproduction (12,(18)(19)(20)(21)(22). The mode of inheritance of the color morphs is unknown. RESULTS Carotenoid and pterin pigments underlie pigmentation differencesWe began by determining the biochemical and cellular basis of pigmentation differences among morphs. Using electron microscopy (TEM), we found that the ventral skin of all morphs contained the same set of dermal pigment cells arranged as three superimposed 6 layers (xantophores, iridophores, and melanophores; Fig. 1C). The iridophore layer was thinner in orange individuals compared to yellow and white, but the most noticeable difference among morphs was observed in the...

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Possible anti-inflammatory effect of carvacrol was evaluated by in vitro cyclooxygenase-2 (COX-2) assay. Carvacrol inhibited production of prostaglandin E(2) catalysed by COX-2 with an IC(50) value of 0.8 microM what is practically the same concentration as the IC(50) obtained for the standard inhibitors indomethacin and NS-398 with values of 0.7 microM and 0.8 microM, respectively. The COX-1 was inhibited approximately at the same rate (IC(50) of 0.7 microM for carvacrol), which suggests non-selective inhibition of both enzyme isoforms. The results of the study demonstrate possible anti-inflammatory potential of this compound due to the inhibition of inducible COX-2 isoform.

Dithymoquinone, thymohydroquinone, thymol and thymoquinone, compounds derived from N. sativa seeds, were investigated for their in vitro anti-inflammatory activities using cyclooxygenase-1 (COX-1) and -2 (COX-2) assays. Our results show that all substances tested possess significant inhibitory activity against at least one COX form at concentrations comparable to the active one of indomethacin. Thymol was the most active against COX-1 with an IC (50) value of 0.2 microM while thymohydroquinone and thymoquinone exhibited the strongest inhibitory effect on COX-2 with IC (50) values of 0.1 and 0.3 microM, respectively. Moreover, dithymoquinone and thymoquinone showed a limited COX-2-specific inhibition. We conclude that dithymoquinone, thymohydroquinone, thymol and thymoquinone can participate in the general anti-inflammatory activity of N. sativa and suggest that these agents should be further studied for possible use as non-steroidal anti-inflammatory drugs.