Permanent genetic changes in tardigrades help shed light on their incredible resilience

Some species of tardigrades are very and unusually resilient to various extreme conditions fatal to most other life forms. The genetic basis of these exceptional abilities remains elusive.

For the first time, researchers from the University of Tokyo have successfully edited genes using the CRISPR technique in a highly resilient tardigrade species, previously impossible to study with genome editing tools. The work was published in PLoS Genetics.

Successful delivery of CRISPR to an asexual tardigrade species directly produces genetically engineered offspring. Designing and editing specific tardigrade genes allows researchers to study which ones are responsible for tardigrade resilience and how that resilience may work.

If you’ve heard of tardigrades, you’ve no doubt heard of their unusual abilities to survive situations such as extreme heat, cold, drought, and even the vacuum of space, which different members of the species. So naturally, they attract researchers eager to explore these new developments, not only out of curiosity, but also to think about the applications that could one day be possible if we discovered their secrets.

“To understand the superpowers of tardigrades, we first need to understand how their genes work,” said Associate Professor Takekazu Kunieda of the Department of Biological Sciences.

“My team and I developed a method to modify genes – adding, removing or overwriting them – as you would in computer data, in a very tolerant species of tardigrade, Ramazzottius varieornatus. This may now enable researchers to study the genetic traits of the tardigrade as they might more established laboratory animals, such as fruit flies or nematodes.

The team used a recently developed technique called direct parental CRISPR (DIPA-CRISPR), based on the now-famous CRISPR gene-editing technique, which can serve as a genetic scalpel to cut and modify specific genes more efficiently than ever before. DIPA-CRISPR has the advantage of being able to affect the genome of a target organism’s offspring and has previously been shown to work on insects, but this is the first time it has been used on non-organisms. -insects, notably tardigrades.

Ramazzottius varieornatus is an all-female species that reproduces asexually, and almost all offspring were found to have two identical copies of the same edited code, unlike other animals, making it an ideal candidate for DIPA-CRISPR.

“We simply needed to inject CRISPR tools programmed to target specific genes for deletion in a parent’s body in order to obtain edited offspring, known as ‘knock-out’ editing,” said Koyuki Kondo, project researcher at the time of the study (currently assistant professor in the Department of Life Sciences, Chiba Institute of Technology).

“We could also obtain genetically modified offspring by injecting additional DNA fragments that we wish to include; this is called knock-in editing. The availability of knock-in editing allows Researchers can precisely edit the genomes of tardigrades, allowing them to, for example, control how individual genes are expressed or exhibit gene functions.

The main resilience trait demonstrated by this species is its ability to survive extreme dehydration for extended periods of time. This was previously shown to be due in part to a particular type of gel protein present in their cells. And this trait is interesting because it has also been applied to human cells.

Kunieda and other tardigrade researchers think it’s worth exploring whether an entire human organ could one day be successfully dehydrated and rehydrated without degradation. If possible, it could revolutionize the way organs are donated, transported and used in surgery to save lives.

“I understand that some people are concerned about gene editing, but we carried out the gene editing experiments under well-controlled conditions and secured the edited organisms in a closed compartment,” Kunieda said.

“CRISPR can be an incredible tool for understanding life and facilitating useful applications that can positively impact the world. Tardigrades not only offer us a glimpse of the medical advances that might be possible, but their range of remarkable traits means that “They have had an incredible evolutionary story, one that we hope to tell by comparing their genomes to closely related creatures using our new DIPA-CRIPSR-based technique.