title: Isolation and characterization of the CYP2D6 gene in Felidae with comparison to other mammals.
abstract: The highly polymorphic CYP2D6 protein metabolizes about 25% of commonly used drugs and underlies a broad spectrum of drug responses among individuals. In contrast to extensive knowledge on the human CYP2D6 gene, little is known about the gene in non-human mammals. CYP2D6 mRNA from 23 cats (Felidae) spanning seven species were compared to available CYPD6 sequences in ten additional mammals and multiple allelic variants in humans. A relatively high mean dN/dS ratio (0.565) was observed, especially within Felidae. Pairwise dN/dS ratios were non-monotonically distributed with respect to evolutionary distance suggesting either positive selection or retention of slightly deleterious mutations. Positive selection on specific codons, most notably in regions involved in substrate recognition and membrane anchoring is supported and the possible influence of diet on specific amino acid changes in substrate binding sites is discussed.
authors.affiliation: Karl-Franzens Universität Graz, Institut für Zoologie, Universitätsplatz 2, A-8010 Graz, Austria.
authors.forename: Tamara
authors.initials: T
authors.lastname: Schenekar
authors.forename: Kathrin A
authors.initials: KA
authors.lastname: Winkler
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Troyer
authors.forename: Steven
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001499:Bayes Theorem; D002415:Cats; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D019143:Evolution, Molecular; D045989:Felidae / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D054643:INDEL Mutation; D016013:Likelihood Functions; D008957:Models, Genetic; D020125:Mutation, Missense; D009245:NADH Dehydrogenase / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D017354:Point Mutation; D017433:Protein Structure, Secondary; D017422:Sequence Analysis, DNA
chemical_list: D000596:Amino Acids; D009687:Nuclear Proteins; D019389:Cytochrome P-450 CYP2D6; D009245:NADH Dehydrogenase