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A complete Axolotl genome could pave the way for the regeneration of human tissue



Axolotl are aquatic salamanders with exceptional regenerative capabilities.
Image: IMP

The delightful and enigmatic axolotl is capable of regenerating many different parts of the body including limbs, organs and even parts of its brain. Scientists hope that a deeper understanding of these extraordinary abilities can help make this type of tissue regeneration possible for humans. With today's news about the first complete axolotl genome, researchers can finally solve the puzzles.

Axolotl are tiny aquatic salamanders whose only habitat is located in a lake near Mexico City. Many animals such as frogs, starfish and flatworms can regenerate tissues, but Axolotl is unique in that it can regenerate many different body parts throughout its life cycle, including the limbs, tail, heart, lungs, eyes, spinal cord and up to half of its brain ,

In a scientific premiere, researchers from the University of Kentucky have put together the axolotl genome, the details of which were published today in Genome Research. That may not sound so impressive, as many animals have sequenced their genomes in recent years. But keep in mind the sheer size and complexity of the Axolotl genome, which consists of 32 gigabases or 32 billion base pairs.

"The axolotl genome is ten times larger than the human genome and is divided into 14 chromosomes. Think of it as a giant picture puzzle board, where the ultimate goal is to create 14 large pieces from each piece of the puzzle. "Prayag Murawala, a geneticist at the Research Institute of Molecular Pathology in Vienna, who is not working on the institute's new study, said Gizmodo. "Building blocks of these 14 puzzles can be obtained through various sequencing technologies. The results of the sequencing, however, do not tell where each building block lies. "

Indeed, the work done so far in the Axolotl genome has produced a tremendous amount of genetic data, but the challenge was to get each puzzle block right in the right place. A genome needs to be assembled in the right order so that scientists can really understand how it works.

Image: AP

Genome sequencing and assembly are iterative processes, according to Randal Voss, co-author of the new study and professor at the University of Kentucky's Research Center for Spinal Cord and Brain Injury. Last year, his team had reached a point where there were a manageable number of pieces to work on, about 125,000 large DNA pieces, but still had to be organized into 14 extremely long linear DNA puzzles.

"We did that with one of the most basic concepts in genetics – linkage mapping," Voss told Gizmodo, "If you find that parts of the DNA are inherited together, they must be close to each other." [19659005] To analyze the genetic link, Voss used tissue generated and frozen 18 years ago by crossing Axolotl into tiger salamanders and took three years to complete these crosses, with the first generation first crosses in 1997 and the second Crosses of the second generation carried out in 2000. With these crosses, Voss identified with the co-author of the study, Jeramiah Smith, genomic regions in the sense of linkage mapping to explain certain aspects of Axolotl's growth and development.Other genetic mapping studies were conducted in

"Fast forward to 2015, Jeramiah had the clever idea of ​​DNA from Ind To sequence individuals of these crosses, "Voss explained," and create a genome map that allowed the arrangement of the approximately 125,000 large pieces of DNA into whole chromosomes. It worked!

Now that researchers have a nearly complete Axolotl genome – the new assembly still needs some fine-tuning (more on that in a nutshell) – they can now do the work together with others identifying the genes responsible for the regeneration of axolotid tissue are responsible. In this way, scientists may be able to regenerate tissue in humans, facilitating limb and skin regrowth, spinal cord repair, and organ healing. This is not empty speculation; The study was funded by the US National Institutes of Health and the US Department of Defense.

"We need all the data to understand how salamanders can regenerate tissue," Voss said. "The DOD is interested in maintaining the Axolotl for research in regenerative medicine, as it promises to demonstrate regenerative repair therapies for finger and hand injuries in combat. This promise is now realized with a complete genome assembly.

Image: IMP

Murawala is particularly excited about the potential for cardiac breakthroughs.

"Axolotls are known to regenerate their hearts," he told Gizmodo. "You can cut up to 30 percent of your heart, and they heal their hearts without defects or scars. "

During their research, Voss and Smith discovered a mutated axolotl that could not repair his heart, which led to the identification of a mutation in their gene tnnt2 Identifying this gene, along with other genes required for axolotl production, will enable scientists to identify "regenerative roadblocks in mammals" in the words of Murawala.

"As the Axolotl research community, we should all be excited about this current work because it's a resource we can all use in our biological studies. "

Jessica Whi ted, assistant professor at Harvard University, Department of Stem Cells and Regenerative Biology, described the new work as a "groundbreaking study." this alone is a valuable resource, but also serves as an important proof-of-concept for genetic research on axolotrons.

"Here they have created a physical map that relates many sites in the genome. For example, it was determined which genes are on the same chromosome and how far apart they are, "Whited told Gizmodo. "It is likely that the resolution of these techniques will continue to increase. However, as an Axolotl research community, we should all look forward to this current work because we can all use it in our biological studies.

As mentioned earlier, sequencing and assembly of genomes is still an iterative process of doing work. The construction of a chromosome plane for the Axolotl is undoubtedly a great achievement, but Voss and his colleagues are now looking to take the next step in making the assembly even better.

Nature is amazing and has already solved many problems for us. All we have to do is find out the nuts and bolts. In the end, tissue regeneration in humans may not work exactly as it does with salamanders. But if we can use it on a broad scale, it will be a paradigm shift for medicine.

[ Genome Research]


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