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

Cytochrome P450 is an important enzyme that metabolizes a variety of chemicals, including exogenous substances, such as drugs and environmental chemicals, and endogenous substances, such as steroids, fatty acids, and cholesterol. Some CYPs show interspecific differences in terms of genetic variation...

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Main Authors: Kanami Watanabe, Mitsuki Kondo, Yoshinori Ikenaka, Shouta M. M. Nakayama, Mayumi Ishizuka
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Animals
Subjects:
Online Access:https://www.mdpi.com/2076-2615/13/12/1939
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author Kanami Watanabe
Mitsuki Kondo
Yoshinori Ikenaka
Shouta M. M. Nakayama
Mayumi Ishizuka
author_facet Kanami Watanabe
Mitsuki Kondo
Yoshinori Ikenaka
Shouta M. M. Nakayama
Mayumi Ishizuka
author_sort Kanami Watanabe
collection DOAJ
description Cytochrome P450 is an important enzyme that metabolizes a variety of chemicals, including exogenous substances, such as drugs and environmental chemicals, and endogenous substances, such as steroids, fatty acids, and cholesterol. Some CYPs show interspecific differences in terms of genetic variation. As little is known about the mechanisms of elephant metabolism, we carried out a comparative genomic and phylogenetic analysis of CYP in elephants. Our results suggest that elephant CYP genes have undergone independent duplication, particularly in the CYP2A, CYP2C, and CYP3A genes, a unique cluster specific to elephant species. However, while CYP2E and CYP4A were conserved in other Afrotheria taxa, their decay in elephants resulted in genetic dysfunction (pseudogene). These findings outline several remarkable characteristics of elephant CYP1–4 genes and provide new insights into elephant xenobiotic metabolism. Further functional investigations are necessary to characterize elephant CYP, including expression patterns and interactions with drugs and sensitivities to other chemicals.
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spelling doaj.art-f007f6f7d1174d26861c281547e834e82023-11-18T08:58:21ZengMDPI AGAnimals2076-26152023-06-011312193910.3390/ani13121939A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4AKanami Watanabe0Mitsuki Kondo1Yoshinori Ikenaka2Shouta M. M. Nakayama3Mayumi Ishizuka4Laboratory of Toxicology, Department of Environmental Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanNational Institute for Environmental Studies (NIES) Biodiversity Division, Ecological Risk Assessment and Control Section, Tsukuba 305-8506, JapanLaboratory of Toxicology, Department of Environmental Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanLaboratory of Toxicology, Department of Environmental Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanLaboratory of Toxicology, Department of Environmental Veterinary Science, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, JapanCytochrome P450 is an important enzyme that metabolizes a variety of chemicals, including exogenous substances, such as drugs and environmental chemicals, and endogenous substances, such as steroids, fatty acids, and cholesterol. Some CYPs show interspecific differences in terms of genetic variation. As little is known about the mechanisms of elephant metabolism, we carried out a comparative genomic and phylogenetic analysis of CYP in elephants. Our results suggest that elephant CYP genes have undergone independent duplication, particularly in the CYP2A, CYP2C, and CYP3A genes, a unique cluster specific to elephant species. However, while CYP2E and CYP4A were conserved in other Afrotheria taxa, their decay in elephants resulted in genetic dysfunction (pseudogene). These findings outline several remarkable characteristics of elephant CYP1–4 genes and provide new insights into elephant xenobiotic metabolism. Further functional investigations are necessary to characterize elephant CYP, including expression patterns and interactions with drugs and sensitivities to other chemicals.https://www.mdpi.com/2076-2615/13/12/1939cytochrome P450genome databasephylogenetics treeAsian elephantAfrican elephantAfrotheria
spellingShingle Kanami Watanabe
Mitsuki Kondo
Yoshinori Ikenaka
Shouta M. M. Nakayama
Mayumi Ishizuka
A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4A
Animals
cytochrome P450
genome database
phylogenetics tree
Asian elephant
African elephant
Afrotheria
title A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4A
title_full A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4A
title_fullStr A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4A
title_full_unstemmed A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4A
title_short A Comparative Genomic and Phylogenetic Investigation of the Xenobiotic Metabolism Enzymes of Cytochrome P450 in Elephants Shows Loss in CYP2E and CYP4A
title_sort comparative genomic and phylogenetic investigation of the xenobiotic metabolism enzymes of cytochrome p450 in elephants shows loss in cyp2e and cyp4a
topic cytochrome P450
genome database
phylogenetics tree
Asian elephant
African elephant
Afrotheria
url https://www.mdpi.com/2076-2615/13/12/1939
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