Adaptations to a Subterranean Environment\nand Longevity Revealed by the Analysis\nof Mole Rat Genomes

Subterranean mammals spend their lives in dark,\nunventilated environments that are rich in carbon dioxide\nand ammonia and low in oxygen. Many of these\nanimals are also long-lived and exhibit reduced aging-associated\ndiseases, such as neurodegenerative\ndisorders and cancer. We sequenced the genome of\nthe Damaraland mole rat (DMR, Fukomys damarensis)\nand improved the genome assembly of the naked\nmole rat (NMR, Heterocephalus glaber). Comparative\ngenome analyses, along with the transcriptomes of\nrelated subterranean rodents, revealed candidate molecular\nadaptations for subterranean life and longevity,\nincluding a divergent insulin peptide, expression\nof oxygen-carrying globins in the brain, prevention of\nhigh CO2-induced pain perception, and enhanced\nammonia detoxification. Juxtaposition of the genomes\nof DMR and other more conventional animals with the\ngenome of NMR revealed several truly exceptional\nNMR features: unusual thermogenesis, an aberrant\nmelatonin system, pain insensitivity, and unique processing\nof 28S rRNA. Together, these genomes and\ntranscriptomes extend our understanding of subterranean\nadaptations, stress resistance, and longevity.