Researchers have sequenced the entire genome of Ambystoma mexicanum, the Mexican axolotl species notable for its exceptional ability to regenerate whole body parts, even severed spinal cord and retinal tissue, in a matter of weeks. According to the paper, published yesterday in Nature, this is the largest genome ever to be sequenced and will be a powerful tool for studying the molecular basis of limb regrowth and other types of regeneration.
The research was done at the Research Institute of Molecular Pathology (IMP) in Vienna where one of the largest axolotl colonies is maintained. Working with the creature over many years, the team was able to amass an extensive molecular toolkit to study the axolotl. They were thus able to identify cells that initiate regeneration and describe the molecular pathways that control this process, but had previously been unable to obtain full genomic data due to its size. At 32 billion base pairs, the axolotl’s genome is more than ten times larger than the human genome.
To take on this sequencing challenge, the IMP team partnered with several other institutes to sequence a total of 72,435,954 long reads from the axolotl’s genome. Specially developed software systems were used to assemble the genome from these millions of pieces.
Analysis of the genome has already returned several features that appear unique to the axolotl. One such feature is the absence of an essential developmental gene called PAX3 whose functions have been taken over instead by a gene named PAX7. Both genes play roles in muscle and neural development.
"We now have the map in our hands to investigate how complicated structures such as legs can be re-grown", says Sergej Nowoshilow, co-first author of the study and a postdoctoral fellow at the IMP. "This is a turning point for the community of scientists working with axolotl, a real milestone in a research adventure that started more than 150 years ago." The sequenced genome is now publicly available for researchers to access.
Image: After being injured, an axolotl can regrow bones, muscles and nerves in the right places. The decoding of the genome of the Mexican axolotl Ambystoma mexicanu will provide researchers with key insights into the process of tissue regeneration. Image courtesy of IMP.