Beaver and Naked Mole Rat Genomes Reveal Common Paths to Longevity

Cell Rep. 2020 Jul 28;32(4):107949. doi: 10.1016/j.celrep.2020.107949.


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.

Keywords: aging; beaver; chromosome-level assembly; evolutionary analyses; gene expression; genome; long-lived rodents; longevity; naked mole rat; stress resistance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / genetics
  • Animals
  • Genome / genetics
  • Longevity / genetics*
  • Models, Animal
  • Mole Rats / genetics*
  • Rodentia / genetics*
  • Species Specificity
  • Transcriptome / genetics