Specific Gene Duplication and Loss of Cytochrome P450 in Families 1-3 in Carnivora (Mammalia, Laurasiatheria)

SIMPLE SUMMARY: In this study we investigated the specific duplication and loss events of cytochrome P450 (CYP) genes in families 1-3 in Carnivora. These genes have been recognized as essential detoxification enzymes, and, using genomic data, we demonstrated a synteny analysis of the CYP coding cluster and a phylogenetic analysis of these genes. We discovered the CYP2Cs and CYP3As expansion in omnivorous species such as the badger, the brown bear, the black bear, and the dog. Furthermore, phylogenetic analysis revealed the evolution of CYP2Cs and 3As in Carnivora. These findings are essential for the appropriate estimation of pharmacokinetics or toxicokinetic in wild carnivorans. ABSTRACT: Cytochrome P450s are among the most important xenobiotic metabolism enzymes that catalyze the metabolism of a wide range of chemicals. Through duplication and loss events, CYPs have created their original feature of detoxification in each mammal. We performed a comprehensive genomic analysis to reveal the evolutionary features of the main xenobiotic metabolizing family: the CYP1-3 families in Carnivora. We found specific gene expansion of CYP2Cs and CYP3As in omnivorous animals, such as the brown bear, the black bear, the dog, and the badger, revealing their daily phytochemical intake as providing the causes of their evolutionary adaptation. Further phylogenetic analysis of CYP2Cs revealed Carnivora CYP2Cs were divided into CYP2C21, 2C41, and 2C23 orthologs. Additionally, CYP3As phylogeny also revealed the 3As’ evolution was completely different to that of the Caniformia and Feliformia taxa. These studies provide us with fundamental genetic and evolutionary information on CYPs in Carnivora, which is essential for the appropriate interpretation and extrapolation of pharmacokinetics or toxicokinetic data from experimental mammals to wild Carnivora.