Ramazzottius varieornatus is one of the most stress-tolerant species of water bear, or tardigrade (A). When there is no water in their environment, the tardigrade shrinks by losing body water and enters an almost completely dehydrated dormant state termed anhydrobiosis (B). The dehydrated tardigrade exhibits extraordinary tolerance against a variety of extreme conditions, including intense radiation. [Sae Tanaka, Hiroshi Sagara, Takekazu Kunieda]
For the microscopic, six-legged water bear, or tardigrade, the ability to tolerate extreme conditions just comes naturally. While the water bear’s extremotolerance doesn’t come naturally to cultured human cells, it can be borrowed.
Ultimately, the water bear is so resilient because of its genetic endowment, as a group of Japanese researchers have confirmed, at least with respect to the water bear’s ability to tolerate intense radiation. When the researchers transferred one particular water bear gene to human cells, the gene produced a DNA-protecting protein, which helped the human cells survive otherwise fatal amounts of radiation damage. Most remarkably, the human cells did not appear to find the gene particularly disruptive. They retained the ability to divide.
Details of the researchers’ work appeared September 20 in the journal Nature Communications, in an article entitled, “Extremotolerant Tardigrade Genome and Improved Radiotolerance of Human Cultured Cells by Tardigrade-Unique Protein.” The article describes how University of Tokyo researchers determined a high-quality genome sequence for Ramazzottius varieornatus, a water bear that is known to survive exposure to high doses of radiation. Using this full genome, they found evidence of a previously unknown protein that appears to confer radiotolerance. They named it Damage Suppressor—Dsup, for short.
Key to the scientists’ analysis was an evaluation of how gene expression profiles changed for the water bear, depending on whether it was in a dehydrated or rehydrated state. The water bear, the scientists noted, is most resilient to extreme conditions when it is in the dehydrated state.
“Precise gene repertoire analyses reveal the presence of a small proportion (1.2% or less) of putative foreign genes, loss of gene pathways that promote stress damage, expansion of gene families related to ameliorating damage, and evolution and high expression of novel tardigrade-unique proteins,” the authors of the Nature Communications article wrote. “Minor changes in the gene expression profiles during dehydration and rehydration suggest constitutive expression of tolerance-related genes.”
The researchers focused on tardigrade-unique proteins, particularly those demonstrating an ability to associate with DNA. They isolated the chromatin fraction from the tardigrade and used tandem mass spectrometry to identify the proteins contained in the bands selective to the chromatin fraction. Only one protein—Dsup—was found to co-localize with nuclear DNA. When the gene for Dsup was engineered into human cells, the Dsup protein showed a similar capacity for co-localization.
Next, the scientists exposed the Dsup-expressing human cells to radiation: “Using human cultured cells, we demonstrate that a tardigrade-unique DNA-associating protein suppresses X-ray-induced DNA damage by ∼40% and improves radiotolerance,” the researcher reported. “These findings indicate the relevance of tardigrade-unique proteins to tolerability and tardigrades could be a bountiful source of new protection genes and mechanisms.”
“What's astonishing is that previously, molecules that repair damaged DNA were thought to be important for tolerating radiation,” noted Takuma Hashimoto, Ph.D., one of the lead authors and a researcher at the University of Tokyo. “On the contrary, Dsup works to minimize the harm inflicted on the DNA.”
The University of Tokyo scientists believe that their precise tardigrade genome sequence is a treasure trove of other Dsup-like proteins and that more of these molecules that increase the creature's resilience will be found in future research.