title: Evidence for functional convergence in genes upregulated by herbivores ingesting plant secondary compounds.
abstract: BACKGROUND
  Nearly 40 years ago, Freeland and Janzen predicted that liver biotransformation enzymes dictated diet selection by herbivores. Despite decades of research on model species and humans, little is known about the biotransformation mechanisms used by mammalian herbivores to metabolize plant secondary compounds (PSCs). We investigated the independent evolution of PSC biotransformation mechanisms by capitalizing on a dramatic diet change event-the dietary inclusion of creosote bush (Larrea tridentata)-that occurred in the recent evolutionary history of two species of woodrats (Neotoma lepida and N. bryanti).
  
  
  RESULTS
  By comparing gene expression profiles of two populations of woodrats with evolutionary experience to creosote and one population naïve to creosote, we identified genes either induced by a diet containing creosote PSCs or constitutively higher in populations with evolutionary experience of creosote. Although only one detoxification gene (an aldo-keto reductase) was induced by both experienced populations, these populations converged upon functionally equivalent strategies to biotransform the PSCs of creosote bush by constitutively expressing aldehyde and alcohol dehydrogenases, Cytochromes P450s, methyltransferases, glutathione S-transferases and sulfotransferases. The response of the naïve woodrat population to creosote bush was indicative of extreme physiological stress.
  
  
  CONCLUSIONS
  The hepatic detoxification system of mammals is notoriously complex, with hundreds of known biotransformation enzymes. The comparison herein of woodrat taxa that differ in evolutionary and ecological experience with toxins in creosote bush reveals convergence in the overall strategies used by independent species after a historical shift in diet. In addition, remarkably few genes seemed to be important in this dietary shift. The research lays the requisite groundwork for future studies of specific biotransformation pathways used by woodrats to metabolize the toxins in creosote and the evolution of diet switching in woodrats. On a larger level, this work advances our understanding of the mechanisms used by mammalian herbivores to process toxic diets and illustrates the importance of the selective relationship of PSCs in shaping herbivore diversity.
authors.affiliation: Department of Biology, 257 South 1400 East, University of Utah, Salt Lake City, UT 84112, USA. malenke@biology.utah.edu.
authors.forename: Jael R
authors.initials: JR
authors.lastname: Malenke
authors.forename: Michele M
authors.initials: MM
authors.lastname: Skopec
authors.forename: M Denise
authors.initials: MD
authors.lastname: Dearing
mesh_terms: D000818:Animals; D005075:Biological Evolution; D003407:Creosote / Q000378:metabolism*; D004032:Diet; D005260:Female; D060434:Herbivory; D008658:Inactivation, Metabolic; D008297:Male; D016205:Sigmodontinae / Q000145:classification / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D003407:Creosote