The genome of North American beaver provides insights into the mechanisms of its longevity and cancer resistance

Zhang, Q.; Tombline, G.; Ablaeva, J.; Zhang, L.; Zhou, X.; Smith, Z.; Xiaoli, A. M.; Wang, Z.; Lin, J.-R.; Jabalameli, M. R.; Mitra, J.; Nguyen, N.; Vijg, J.; Seluanov, A.; Gladyshev, V. N.; Gorbunova, V.; Zhang, Z. D.

doi:10.1101/2020.06.25.171322

bioRxiv · 10.1101/2020.06.25.171322

The genome of North American beaver provides insights into the mechanisms of its longevity and cancer resistance

Zhang, Q.·Tombline, G.·Ablaeva, J.·Zhang, L.·Zhou, X.·Smith, Z.·Xiaoli, A. M.·Wang, Z.·Lin, J.-R.·Jabalameli, M. R.·Mitra, J.·Nguyen, N.·Vijg, J.·Seluanov, A.·Gladyshev, V. N.·Gorbunova, V.·Zhang, Z. D.

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Abstract

The North American beaver (Castor canadensis) is an exceptionally long-lived and cancer-resistant rodent species, and thus an excellent model organism for comparative genomic studies of longevity. Here, we utilize a significantly improved beaver genome assembly to assess evolutionary changes in gene coding sequences, copy number, and expression. We found that the beaver Aldh1a1, a stem cell marker gene encoding an enzyme required for detoxification of ethanol and aldehydes, is expanded (~10 copies vs. two in mouse and one in human). We also show that the beaver cells are more resistant to ethanol, and beaver liver extracts show higher ability to metabolize aldehydes than the mouse samples. Furthermore, Hpgd, a tumor suppressor gene, is uniquely duplicated in the beaver among rodents. Our evolutionary analysis identified beaver genes under positive selection which are associated with tumor suppression and longevity. Genes involved in lipid metabolism show positive selection signals, changes in copy number and altered gene expression in beavers. Several genes involved in DNA repair showed a higher expression in beavers which is consistent with the trend observed in other long-lived mammals. In summary, we identified several genes that likely contribute to beaver longevity and cancer resistance, including increased ability to detoxify aldehydes, enhanced tumor suppression and DNA repair, and altered lipid metabolism.

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Zhang, Q., Tombline, G., Ablaeva, J., Zhang, L., Zhou, X., Smith, Z., Xiaoli, A. M., Wang, Z., Lin, J.-R., Jabalameli, M. R., Mitra, J., Nguyen, N., Vijg, J., Seluanov, A., Gladyshev, V. N., Gorbunova, V., Zhang, Z. D.. 2020-06-27. The genome of North American beaver provides insights into the mechanisms of its longevity and cancer resistance. https://doi.org/10.1101/2020.06.25.171322

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