Permanent gene changes for tardigrades help shed light on their amazing resilience

Certain species of tardigrades are highly and extremely resilient to various extreme conditions fatal to most other life forms. The genetic basis for these extraordinary 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 that was previously impossible to study with genome editing tools. The work was published in PLoS Genetics.

Successful delivery of CRISPR into an asexual tardigrade species directly produces gene-modified offspring. Designing and editing specific tardigrade genes allows researchers to investigate which are responsible for delayed resilience and how such resilience might work.

If you’ve heard of tardigrades, then you’ve no doubt heard of their unusual abilities to survive things like extreme heat, cold, drought, and even the vacuum of space that various members of the species possess. So naturally, they attract researchers eager to explore these innovations, not just out of curiosity, but also to see what applications might one day be possible if we learn their secrets.

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

“My team and I have 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 allow researchers to study delayed genetic traits as they can create more lab-based animals, such as fruit flies or nematodes.”

The team used a recently developed technique called direct parenteral 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 in a more efficient 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 in insects, but this is the first time it has been used in non-insect organisms that include 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 had to inject CRISPR tools programmed to target specific genes for deletion into a parent’s body to obtain modified offspring, known as ‘knock-out’ editing,” said Koyuki Kondo, project researcher at the time of study (currently assistant professor in the Department of Life Sciences at Chiba Institute of Technology).

“We can also get gene-edited offspring by injecting additional DNA fragments that we want to include; this is called ‘knock-in’ editing. The availability of knock-in editing allows researchers to precisely edit delayed genomes, allowed them to, for example, control how individual genes are expressed, or display gene functions.”

The main feature of resilience shown by this species is their ability to survive extreme dehydration for long periods. This was previously shown to be partly due to a special type of gel protein in their cells. And this feature is interesting as it has also been applied to human cells.

Kunieda and other late researchers think it’s worth exploring whether something like an entire human organ could one day be successfully dehydrated and rehydrated without degrading. If this is possible, it could revolutionize the way organs are donated, transported and used in life-saving surgery.

“I understand that some people feel uneasy about gene editing, but we performed the gene editing experiments under well-controlled conditions and secured the edited organisms in a sealed compartment,” Kunieda said.

“CRISPR can be an incredible tool for understanding life and helping with useful applications that can positively impact the world. Tardigrades not only provide us with a glimpse of what medical progress might be possible, but “The range of their extraordinary traits means they had a remarkable evolutionary history, one we hope to reveal as we compare their genomes with closely related creatures using our new DIPA-CRIPSR-based technique.”