Vadim N. Gladyshev, PhD

Deep Living

A team led by Vadim N. Gladyshev, PhD, professor of Medicine at the BWH Department of Medicine, has sequenced the genome of the Damaraland mole rat (DMR) and improved the genome sequence of the naked mole rat (NMR). The DMR and NMR are subterranean African mammals that live in dark, unventilated environments. The genomes and transcriptomes of these animals then were compared to the transcriptomes (gene expression profiles) of related subterranean rodents.

African mole rats live in habitats high in carbon dioxide (CO2) and ammonia and low in oxygen. These conditions are harmful to mice and rats, yet mole rats are exceptionally long-lived and display resistance to age-related diseases, such as neurodegenerative disorders and cancer. The researchers sought to determine the molecular mechanisms responsible for these traits.

There were several molecular adaptations identified that may enable the DMR and NMR to survive in such harsh conditions. These include a divergent insulin peptide that may be less biologically active, expression of globin proteins that carry oxygen in the brain, changes in a voltage-gated sodium channel to decrease high CO2-induced pain perception, and enzymatic alterations for enhanced ammonia detoxification. Furthermore, the NMR displayed several unique characteristics such as ineffective thermogenesis likely due to alterations in the heat-generating protein, UCP1; no expression of cognate melatonin receptors; pain insensitivity due to a lack of the neuropeptides substance P and calcitonin gene-related peptide; and unusual ribosomal RNA processing.

“Together, these genomes and transcriptomes extend our understanding of subterranean adaptations, stress resistance, and longevity,” said Gladyshev.

The study was published Sept. 11, 2014, in Cell Reports.