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Duplication, Loss, and Evolutionary Features of Specific UDP-Glucuronosyltransferase Genes in Carnivora (Mammalia, Laurasiatheria)

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Title: Duplication, Loss, and Evolutionary Features of Specific UDP-Glucuronosyltransferase Genes in Carnivora (Mammalia, Laurasiatheria)
Authors: Kondo, Mitsuki Browse this author
Ikenaka, Yoshinori Browse this author
Nakayama, Shouta M. M. Browse this author
Kawai, Yusuke K. Browse this author
Ishizuka, Mayumi Browse this author →KAKEN DB
Keywords: wildlife
xenobiotic metabolism
in silico analysis
genome database
phase II metabolism
Issue Date: Nov-2022
Publisher: MDPI
Journal Title: Animals
Volume: 12
Issue: 21
Start Page: 2954
Publisher DOI: 10.3390/ani12212954
Abstract: Simple Summary In this study, we clarified the evolutional features of the UGT gene family in Carnivora. We firstly analyzed the gene synteny of UGT1As, 2Bs, ana 2Es and further demonstrated the phylogenetic analysis to reveal the evolutional gene duplication and loss event in Carnivora. We found specific UGT1A duplication in Canidae, brown bear and black bear, and UGT2Bs duplication in Canidae, some Mustelidae, and Ursidae. In addition, we observed gene contraction of UGT1A7-12 in Phocidae, Otariidae, and Felidae. This study strongly suggested closely related Carnivorans also showed significant evolutional differences of UGTs, and further imply the importance of appropriate approaches to assess pharmacokinetics and toxicokinetic from experimental animals. UDP-glucuronosyltransferases (UGTs) are one of the most important enzymes for xenobiotic metabolism or detoxification. Through duplication and loss of genes, mammals evolved the species-specific variety of UGT isoforms. Among mammals, Carnivora is one of the orders that includes various carnivorous species, yet there is huge variation of food habitat. Recently, lower activity of UGT1A and 2B were shown in Felidae and pinnipeds, suggesting evolutional loss of these isoforms. However, comprehensive analysis for genetic or evolutional features are still missing. This study was conducted to reveal evolutional history of UGTs in Carnivoran species. We found specific gene expansion of UGT1As in Canidae, brown bear and black bear. We also found similar genetic duplication in UGT2Bs in Canidae, and some Mustelidae and Ursidae. In addition, we discovered contraction or complete loss of UGT1A7-12 in phocids, some otariids, felids, and some Mustelids. These studies indicate that even closely related species have completely different evolution of UGTs and further imply the difficulty of extrapolation of the pharmacokinetics and toxicokinetic result of experimental animals into wildlife carnivorans.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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