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

Quanwei Zhang, Gregory Tombline, Julia Ablaeva, Lei Zhang, Xuming Zhou, Zachary Smith, Yang Zhao, Alus M. Xiaoli, Zhen Wang, Jhih-Rong Lin, M. Reza Jabalameli, Joydeep Mitra, Nha H. Nguyen, Jan Vijg, Andrei Seluanov, Vadim N. Gladyshev, Vera Gorbunova, Zhengdong Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number109965
JournalCell Reports
Volume37
Issue number6
DOIs
StatePublished - Nov 9 2021

Keywords

  • beaver genome
  • gene expansion
  • gene expression
  • longevity
  • positive selection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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