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Cytochromes P450 and the chemical defensome

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Cytochromes P450 and the chemical defensome
Genomic analyses
Genomic analysis and expression studies of the chemical defensome in marine invertebrates, including mollusks, tunicates, sea urchins, and sea anemones.

For several decades, genes in the cytochrome P450 monooxygenase (CYP) superfamily have been used as potent biomarkers for organic contamination in aquatic vertebrates. Once xenobiotics enter an organism, biotransformation is usually required to enhance elimination or toxicant inactivation. The initial step leading to excretion is generally oxidative modification of chemicals to more hydrophilic products, principally carried out by CYPs. Induction of genes in certain CYP families, principally CYP1, CYP2, and CYP3, are among the most prominent and well-studied responses to xenobiotic exposure. We have been heavily involved in comparative genomic studies to understand the evolution of CYP gene diversity and function.

We have already begun to approach the full complement of CYP sequences expressed in mussels, oysters, sea urchins, tunicates, and sea anemones. The CYP sequences we uncovered in Mytilus provide a foundation for more detailed characterization of CYP functions in bivalves, especially other Mytilidae. Our provisional assignment of sequences to known gene families, including families that are involved in xenobiotic responses in other species, suggests that many of these bivalve CYPs could be involved in defenses against chemicals.
Gene expression

We are working to develop molecular biomarkers for anthropogenic coastal pollution in environmentally and economically important mussels, focusing on the blue mussel Mytilus edulis (Bivalvia: Mytilinae), and on related Mytilus spp. (e.g., M. galloprovincialis).  Global aquaculture production of mussels has at times exceeded 500,000 tons annually, and mussels are an important aquaculture species in New England. Like several other bivalves, Mytilus species have important characteristics of sentinel species useful in pollution biomonitoring. They are distributed in temperate waters in both pelagic ecosystems and brackish estuaries where runoff is at its highest, and are sessile filter feeders, which accumulate a wide range of contaminants. Studies over several decades have consistently shown that contaminant levels in mussel tissues respond to ambient environmental levels and are integrated over a given area (Tripp and Farrington 1984; Munschy et al. 2008).  These features were the foundation of the national and international “Mussel Watch” programs to assess trends in contaminant levels in coastal waters.  Mussels continue to show the presence of new chemicals of concern (Ramu et al. 2007; Booth et al. 2008).

Understanding the effects of chemicals cannot be achieved without knowledge of the diversity of CYP genes and their expression. A comprehensive knowledge of Mytilus CYP and their probable functional relationships to mammalian CYP will provide a lasting foundation, underpinning current or future toxicological research with mussels.  The goal of the proposed work is to identify CYP genes and to establish biomarkers of coastal pollution in the mussel Mytilus edulis and other Mytilus species, by assaying changes in gene expression, in response to experimental and environmental chemical exposures.






Last updated: September 5, 2012
 


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