Beaver and Naked Mole Rat Genomes Reveal Common Paths to Longevity
Xuming Zhou,
Qianhui Dou,
Guangyi Fan,
Quanwei Zhang,
Maxwell Sanderford,
Alaattin Kaya,
Jeremy Johnson,
Elinor K. Karlsson,
Xiao Tian,
Aleksei Mikhalchenko,
Sudhir Kumar,
Andrei Seluanov,
Zhengdong D. Zhang,
Vera Gorbunova,
Xin Liu,
Vadim N. Gladyshev
Affiliations
Xuming Zhou
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, MA 02142, USA
Qianhui Dou
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Guangyi Fan
BGI—Shenzhen, Shenzhen 518083, China
Quanwei Zhang
Albert Einstein College of Medicine, Bronx, NY 10461, USA
Maxwell Sanderford
Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
Alaattin Kaya
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, MA 02142, USA; Department of Biology, Virginia Commonwealth University, Richmond, VA 23284 USA
Jeremy Johnson
Broad Institute of Harvard and MIT, Cambridge, Massachusetts, MA 02142, USA
Elinor K. Karlsson
Broad Institute of Harvard and MIT, Cambridge, Massachusetts, MA 02142, USA; University of Massachusetts Medical School, Worcester, MA 01655, USA
Xiao Tian
Department of Biology, University of Rochester, Rochester, NY 14627, USA; Department of Medicine, University of Rochester, Rochester, NY 14627, USA
Aleksei Mikhalchenko
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Sudhir Kumar
Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
Andrei Seluanov
Department of Biology, University of Rochester, Rochester, NY 14627, USA; Department of Medicine, University of Rochester, Rochester, NY 14627, USA
Zhengdong D. Zhang
Albert Einstein College of Medicine, Bronx, NY 10461, USA
Vera Gorbunova
Department of Biology, University of Rochester, Rochester, NY 14627, USA; Department of Medicine, University of Rochester, Rochester, NY 14627, USA
Xin Liu
BGI—Shenzhen, Shenzhen 518083, China
Vadim N. Gladyshev
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, MA 02142, USA; Corresponding author
Summary: Long-lived rodents have become an attractive model for the studies on aging. To understand evolutionary paths to long life, we prepare chromosome-level genome assemblies of the two longest-lived rodents, Canadian beaver (Castor canadensis) and naked mole rat (NMR, Heterocephalus glaber), which were scaffolded with in vitro proximity ligation and chromosome conformation capture data and complemented with long-read sequencing. Our comparative genomic analyses reveal that amino acid substitutions at “disease-causing” sites are widespread in the rodent genomes and that identical substitutions in long-lived rodents are associated with common adaptive phenotypes, e.g., enhanced resistance to DNA damage and cellular stress. By employing a newly developed substitution model and likelihood ratio test, we find that energy and fatty acid metabolism pathways are enriched for signals of positive selection in both long-lived rodents. Thus, the high-quality genome resource of long-lived rodents can assist in the discovery of genetic factors that control longevity and adaptive evolution.
