Complete naked mole-rat genome preprint: four protein substitutions linked to its longevity also occur in a relative the authors consider short-lived
Complete naked mole-rat genome preprint: four protein substitutions linked to its longevity also occur in a relative the authors consider short-lived
On October 16, a team that included researchers from the University of Cambridge posted a manuscript on bioRxiv. It has not been peer reviewed. The authors assembled the naked mole-rat genome and compared it with that of the Cape dune mole-rat, a solitary relative in the same family of African mole-rats.
In October 2025, Science published a study linking naked mole-rat longevity to four amino acid substitutions in the protein cGAS. In humans and mice, this protein inhibits one pathway for repairing DNA breaks; in naked mole-rats, it remains at the damage site longer and helps repair it. Flies expressing the naked mole-rat protein lived longer than controls, and mice given gene therapy with it had less greying and fewer senescent cells.
These features of the naked mole-rat protein were identified through comparison with mice. However, their common ancestor lived about 73 million years ago, so the differences could have arisen in either lineage. To distinguish features specific to the naked mole-rat from those shared by the family, the authors compared three species. Naked mole-rats live in colonies with a single breeding queen, Ansell’s mole-rats live in family groups, and Cape dune mole-rats live alone. Individuals older than 30, 20 and six years, respectively, have been recorded in captivity. The authors consider the Cape dune mole-rat short-lived.
The Cape dune mole-rat carries the same cGAS variant: all four amino acids occupy the same positions. The authors conclude that the naked mole-rat probably inherited this variant from the family’s common ancestor and that the variant alone does not explain its longevity. The Cape dune mole-rat also has a duplication of Tinf2, a gene whose protein protects chromosome ends, but it has only one intact copy, whereas the naked mole-rat has two.
“The naked mole-rat’s distinctive traits are more likely to depend on gains absent from the Cape dune mole-rat,” the authors write. These gains are additional gene copies, which can be counted reliably only in a fully assembled genome: earlier naked mole-rat assemblies collapsed repetitive regions and similar genes into single copies. In the new assembly, 40 of the 60 chromosomes have no gaps; the remaining chromosomes have gaps only in the most repetitive regions. There are 109 genes that occur as single copies in humans and mice but as multiple copies in the naked mole-rat. Of these, 86 have more copies in the naked mole-rat than in the Cape dune mole-rat.
One is Klf2, whose protein suppresses tumour growth: the Cape dune mole-rat has one copy, the naked mole-rat has 11, and Ansell’s mole-rat has 12. Ansell’s mole-rat is more closely related to the Cape dune mole-rat, yet its Klf2 copy number resembles that of the naked mole-rat. Both species live longer than the Cape dune mole-rat and raise their young cooperatively. The authors suggest two possible explanations: the additional copies arose independently in the two lineages, or they were present in the family’s common ancestor and were lost in the Cape dune mole-rat.
Pms1 is related to genes that repair errors made during DNA replication. The naked mole-rat has six copies, while the Cape dune mole-rat and Ansell’s mole-rat each have one. The copies arose through successive duplications, and all six are transcribed into full-length RNA. This region could be resolved only in the fully assembled genome: a second naked mole-rat genome, from a different colony, still had a gap at this position.
Across 26 species of rodents, moles and shrews, Pms1 expression is higher in longer-lived species in all six tissues examined, according to data published in Cell Metabolism. The preprint states that “it is tempting to speculate that six functional copies provide reserve capacity for genome maintenance.” The roles of Klf2 and Pms1 remain to be tested in naked mole-rat cells and in mice with the relevant sequences inserted into their genomes. Because a single queen produces the offspring in a colony, genome editing in naked mole-rats is currently impractical.