Across insect genomes, the size of the cytochrome P450 monooxygenase (
This study aims to create a database for quantifying the fraction of metabolism of cytochrome P450 isozymes for cancer drugs approved by the
- NSF-PAR ID:
- 10460353
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- CPT: Pharmacometrics & Systems Pharmacology
- Volume:
- 8
- Issue:
- 7
- ISSN:
- 2163-8306
- Page Range / eLocation ID:
- p. 511-519
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract CYP ) gene superfamily varies widely.CYP ome size variation has been attributed to reciprocal adaptive radiations in insect detoxification genes in response to plant biosynthetic gene radiations driven by co‐evolution between herbivores and their chemically defended hostplants. Alternatively, variation inCYP ome size may be due to random “birth‐and‐death” processes, whereby exponential increase via gene duplications is limited by random decay via gene death or transition via divergence. We examinedCYP ome diversification in the genomes of seven Lepidoptera species varying in host breadth from monophagous (Bombyx mori ) to highly polyphagous (Amyelois transitella ).CYP ome size largely reflects the size of Clan 3, the clan associated with xenobiotic detoxification, and to some extent phylogenetic age. Consistently across genomes, familiesCYP 6,CYP 9 andCYP 321 are most diverse andCYP 6AB ,CYP 6AE ,CYP 6B,CYP 9A andCYP 9G are most diverse among subfamilies. Higher gene number in subfamilies is due to duplications occurring primarily after speciation and specialization (“P450 blooms”), and the genes are arranged in clusters, indicative of active duplicating loci. In the parsnip webworm,Depressaria pastinacella , gene expression levels in large subfamilies are high relative to smaller subfamilies. Functional and phylogenetic data suggest a correlation between highly dynamic loci (reflective of extensive gene duplication, functionalization and in some cases loss) and the ability of enzymes encoded by these genes to metabolize hostplant defences, consistent with an adaptive, nonrandom process driven by ecological interactions. -
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Summary In the natural pesticides known as pyrethrins, which are esters produced in flowers of
Tanacetum cinerariifolium (Asteraceae), the monoterpenoid acyl moiety is pyrethric acid or chrysanthemic acid.We show here that pyrethric acid is produced from chrysanthemol in six steps catalyzed by four enzymes, the first five steps occurring in the trichomes covering the ovaries and the last one occurring inside the ovary tissues.
Three steps involve the successive oxidation of carbon 10 (C10) to a carboxylic group by Tc
CHH , a cytochrome P450 oxidoreductase. Two other steps involve the successive oxidation of the hydroxylated carbon 1 to give a carboxylic group by TcADH 2 and TcALDH 1, the same enzymes that catalyze these reactions in the formation of chrysanthemic acid. The ultimate result of the actions of these three enzymes is the formation of 10‐carboxychrysanthemic acid in the trichomes. Finally, the carboxyl group at C10 is methylated by TcCCMT , a member of theSABATH methyltransferase family, to give pyrethric acid. This reaction occurs mostly in the ovaries.Expression in
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Abstract Next‐generation sequencing technologies now allow researchers of non‐model systems to perform genome‐based studies without the requirement of a (often unavailable) closely related genomic reference. We evaluated the role of restriction endonuclease (
RE ) selection in double‐digest restriction‐site‐associatedDNA sequencing (ddRAD seq) by generating reduced representation genome‐wide data using four differentRE combinations. Our expectation was thatRE selections targeting longer, more complex restriction sites would recover fewer loci thanRE with shorter, less complex sites. We sequenced a diverse sample of non‐model arachnids, including five congeneric pairs of harvestmen (Opiliones) and four pairs of spiders (Araneae). Sample pairs consisted of either conspecifics or closely related congeneric taxa, and in total 26 sample pair analyses were tested. Sequence demultiplexing, read clustering and variant calling were performed in thepy program. The 6‐base pair cutterRAD Eco combined with methylated site‐specific 4‐base pair cutterRI MspI produced, on average, the greatest numbers of intra‐individual loci and shared loci per sample pair. As expected, the number of shared loci recovered for a sample pair covaried with the degree of genetic divergence, estimated with cytochrome oxidase I sequences, although this relationship was non‐linear. Our comparative results will prove useful in guiding protocol selection for ddRAD seq experiments on many arachnid taxa where reference genomes, even from closely related species, are unavailable. -
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Objective To obtain the comprehensive transcriptome profile of human citrulline‐specific B cells from patients with rheumatoid arthritis (
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RA patients and healthy individuals. The transcriptome profile of the sorted cells was obtained byRNA ‐sequencing, and expression of key protein molecules was evaluated by aptamer‐basedSOMA scan assay and flow cytometry. The ability of these proteins to effect differentiation of osteoclasts and proliferation and migration of synoviocytes was examined by in vitro functional assays.Results Citrulline‐specific B cells, in comparison to citrulline‐negative B cells, from patients with
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Summary The landmark report (Herbst
et al . 1971) linking prenatal treatment with a synthetic estrogen, diethylstilbestrol (DES ), to cancer at puberty in women whose mothers took the drug while pregnant ushered in an era of research on delayed effects of such exposures on functional outcomes in offspring. An animal model developed in our laboratory at the National Institute of Environmental Health Sciences confirmed thatDES was the carcinogen and exposure toDES caused, as well, functional alterations in the reproductive, endocrine, and immune systems of male and female mice treated in utero.DES was also being used in agriculture and we discovered, at the first meeting onEstrogens in the Environment in 1979 (Estrogens in the Environment, 1980), that many environmental contaminants were also estrogenic. Many laboratories sought to discern the basis for estrogenicity in environmental chemicals and to discover other hormonally active xenobiotics. Our laboratory elucidated howDES and other estrogenic compounds worked by altering differentiation through epigenetic gene imprinting, helping explain the transgenerational effects found in mice and humans. At theWingspread Conference on the Human‐Wildlife Connection in 1991 (Advances in Modern Environmental Toxicology, 1992), we learned that environmental disruption of the endocrine system occurred in many species and phyla, and the term endocrine disruption was introduced. Further findings of transgenerational effects of environmental agents that mimicked or blocked various reproductive hormones and the ubiquity of environmental signals, such as bisphenol A increased concern for human and ecological health. Scientists began to look at other endocrine system aspects, such as cardiovascular and immune function, and other nuclear receptors, with important observations regarding obesity and metabolism. Laboratories, such as ours, are now using stem cells to try to understand the mechanisms by which various environmental signals alter cell differentiation. Since 2010, research has shown that trauma and other behavioral inputs can function as ‘environmental signals,’ can be encoded in gene regulation networks in a variety of cells and organs, and can be passed on to subsequent generations. So now we come full circle: environmental chemicals mimic hormones or other metabolic signaling molecules and now behavioral experience can be transduced into chemical signals that also modify gene expression.
