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

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.

A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4A

“…A phylogenetic analysis and synteny comparison of the CYP2C cluster region was conducted next (Figure 3). The coding loci of CYP2Cs were highly conserved between "helicase lymphoid specific (HELLS)" and the "PDZ and LIM domain 1 (PDLIM1)" (Figure 3A), as was also reported in a previous study [19,29]. The phylogenetic tree showed that CYP2C of elephants can be separated into five different groups; CYP2C19 (clade 1), another group of CYP2C19 (clade 2), CYP2C42 (clade 3), CYP2C21 (clade 4), and CYP2C23 (clade 5).…”

“…CYP2C23 are other genes found in elephants, several herbivores, and carnivores. The CYP2C23 of rats and mice are known as arachidonic acid or eicosanoid metabolizing CYPs [ 50 , 51 ], considered more like endogenous-metabolizing isoforms, which may play a similar role in these taxa [ 19 ].…”

“…In general, if the number of isoforms expands in a particular CYP, this indicates that the gene has been duplicated to adapt to an environment or diet change that has likely exposed the gene to a particular substrate. However, a low or deficient number of isoforms indicates that the gene is no longer exposed to a particular substrate, and its function may have selectively degenerated [ 19 , 20 , 21 ].…”