Isolation and Characterization of the CYP2D6 Gene in Felidae with Comparison to Other Mammals

• Published in: Journal of molecular evolution 2011-02, Vol.72 (2), p.222-231, Article 222
• Main Authors: Schenekar, Tamara, Winkler, Kathrin A., Troyer, Jennifer L., Weiss, Steven
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Amino Acids - chemistry; Animal Genetics and Genomics; Animals; Bayes Theorem; Biomedical and Life Sciences; Cats; Cell Biology; Cytochrome P-450 CYP2D6 - genetics; Evolution, Molecular; Evolutionary Biology; Felidae; Felidae - genetics; Genes; Genetic Variation; Humans; INDEL Mutation; Life Sciences; Likelihood Functions; Mammals; Microbiology; Models, Genetic; Molecular biology; Mutation, Missense; NADH Dehydrogenase - genetics; Nuclear Proteins - genetics; Pharmacology; Plant Genetics and Genomics; Plant Sciences; Point Mutation; Polymorphism; Protein Structure, Secondary; Proteins; Sequence Analysis, DNA
• ISSN: 0022-2844; 1432-1432; 1432-1432
• DOI: 10.1007/s00239-010-9424-1

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 d N /d S ratio (0.565) was observed, especially within Felidae. Pairwise d N /d S 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.