Genomic expansion of Aldh1a1 protects beavers against high metabolic aldehydes from lipid oxidation.

Autor:	Zhang Q; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Tombline G; Department of Biology, University of Rochester, Rochester, NY 14627, USA., Ablaeva J; Department of Biology, University of Rochester, Rochester, NY 14627, USA., Zhang L; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Zhou X; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Smith Z; Department of Biology, University of Rochester, Rochester, NY 14627, USA., Zhao Y; Department of Biology, University of Rochester, Rochester, NY 14627, USA., Xiaoli AM; Departments of Medicine and Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA., Wang Z; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Lin JR; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Jabalameli MR; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Mitra J; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Nguyen N; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Vijg J; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Seluanov A; Department of Biology, University of Rochester, Rochester, NY 14627, USA., Gladyshev VN; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Gorbunova V; Department of Biology, University of Rochester, Rochester, NY 14627, USA., Zhang ZD; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: zhengdong.zhang@einsteinmed.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Nov 09; Vol. 37 (6), pp. 109965.
DOI:	10.1016/j.celrep.2021.109965
Abstrakt:	The North American beaver is an exceptionally long-lived and cancer-resistant rodent species. Here, we report the evolutionary changes in its gene coding sequences, copy numbers, and expression. We identify changes that likely increase its ability to detoxify aldehydes, enhance tumor suppression and DNA repair, and alter lipid metabolism, potentially contributing to its longevity and cancer resistance. Hpgd, a tumor suppressor gene, is uniquely duplicated in beavers among rodents, and several genes associated with tumor suppression and longevity are under positive selection in beavers. Lipid metabolism genes show positive selection signals, changes in copy numbers, or altered gene expression in beavers. Aldh1a1, encoding an enzyme for aldehydes detoxification, is particularly notable due to its massive expansion in beavers, which enhances their cellular resistance to ethanol and capacity to metabolize diverse aldehyde substrates from lipid oxidation and their woody diet. We hypothesize that the amplification of Aldh1a1 may contribute to the longevity of beavers. Competing Interests: Declaration of interests J.V. is a founder of Singulomics. All of the other authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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