Cytochrome P450 2B diversity and dietary novelty in the herbivorous, desert woodrat (Neotoma lepida)

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Publication Type pre-print
School or College School of Medicine
Department Internal Medicine
Creator Thomas, Kirk R.
Other Author Malenke, Jael R.; Magnanou, Elodie; Dearing, M. Denise
Title Cytochrome P450 2B diversity and dietary novelty in the herbivorous, desert woodrat (Neotoma lepida)
Date 2012-01-01
Description Detoxification enzymes play a key role in plant-herbivore interactions, contributing to the on-going evolution of ecosystem functional diversity. Mammalian detoxification systems have been well studied by the medical and pharmacological industries to understand human drug metabolism; however, little is known of the mechanisms employed by wild herbivores to metabolize toxic plant secondary compounds. Using a wild rodent herbivore, the desert woodrat (Neotoma lepida), we investigated genomic structural variation, sequence variability, and expression patterns in a multigene subfamily involved in xenobiotic metabolism, cytochrome P450 2B (CYP2B). We hypothesized that differences in CYP2B expression and sequence diversity could explain differential abilities of woodrat populations to consume native plant toxins. Woodrats from two distinct populations were fed diets supplemented with either juniper (Juniperus osteosperma) or creosote bush (Larrea tridentata), plants consumed by woodrats in their respective desert habitats. We used Southern blot and quantitative PCR to determine that the genomic copy number of CYP2B in both populations was equivalent, and similar in number to known rodent copy number. We compared CYP2B expression patterns and sequence diversity using cloned hepatic CYP2B cDNA. The resulting sequences were very diverse, and clustered into four major clades by amino acid similarity. Sequences from the experimental treatments were distributed non-randomly across a CYP2B tree, indicating unique expression patterns from woodrats on different diets and from different habitats. Furthermore, within each major CYP2B clade, sequences shared a unique combination of amino acid residues at 13 sites throughout the protein known to be important for CYP2B enzyme function, implying differences in the function of each major CYP2B variant. This work is the most comprehensive investigation of the genetic diversity of a detoxification enzyme subfamily in a wild mammalian herbivore, and contributes an initial genetic framework to our understanding of how a wild herbivore responds to critical changes in its diet.
Type Text
Publisher Public Library of Science (PLoS)
Volume 7
Issue 8
First Page 1
Last Page 12
Dissertation Institution University of Utah
Language eng
Bibliographic Citation Malenke, J. R., Magnanou, E., Thomas, K., & Dearing, M. D. (2012). Cytochrome P450 2B diversity and dietary novelty in the herbivorous, desert woodrat (Neotoma lepida). PLoS ONE, 7(8), no. e41510, 1-12.
Rights Management (c) Kirk R. Thomas
Format Medium application/pdf
Format Extent 884,934 bytes
Identifier uspace,17754
ARK ark:/87278/s6wd4jbb
Setname ir_uspace
Date Created 2012-09-20
Date Modified 2012-09-20
ID 708121
Reference URL
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