Scientists Dive Into Axolotl Genome, Looking for Secrets to Regeneration

Scientists Dive Into Axolotl Genome, Looking for Secrets to Regeneration

Its adorableness aside, the Mexican axolotl is a salamander of particular interest to scientists. On the molecular level, the animal seems to have a cheat code for life: It can regenerate its limbs and vital organs, an ability researchers are desperate to better understand for medical applications.

Now, geneticists have gotten a clearer view of the smiling salamander’s genome, rendering it on the chromosomal scale. The research was published this week in the Proceedings of the National Academy of Sciences.

Understanding a genetic structure in complete detail takes a lot of time, far longer than it takes to first report the mapping of a genome, as we did with humans in 2003 and the duck-billed platypus in 2008. Secrets remain shrouded in those purportedly finished genetic codes, so geneticists keep tinkering. Decrypting the axolotl’s genome in particular was a tall order; where bits of a human genome charged with making a protein may span hundreds to thousands of base pairs, in an axolotl, it takes hundreds of thousands of base pairs. Nevertheless, the complete axolotl genome was announced in 2019 by the same team who published the recent research.

Scientists Dive Into Axolotl Genome, Looking for Secrets to Regeneration

“We used some techniques that were related to our earlier classical genetic mapping techniques,” said co-author Jeramiah Smith, a geneticist at the University of Kentucky, in a video call. “But that allowed us to stitch these million base pair things into billion, billion-plus base pair scaffolds that represented the length of chromosomes.”

Axolotls are evolutionary ascetics. While the rest of the salamanders learned how to live amphibiously, the axolotl stayed in the water and evolved to basically stay in its larval phase throughout its life. Comparing the axolotl to a Pokémon is uncannily accurate; a century ago, researchers found that when you fed thyroid tissue to axolotls, they’d occasionally undergo metamorphosis, losing the fern-like gills that sprout from their heads and the tadpole-esque tailfin.

The recent paper specifically looked at how the genome is folded away inside the animal on the molecular level and where the DNA sequences that regulate genes are located in relation to the places where gene transcription starts. That’s remarkable when you consider the scale and extreme compactness of the folding; a human DNA strand is about 1.83 m when stretched out, but an axolotl’s would be over 9.14 m. All that genetic material is being sequestered in the cells of an animal 200 times smaller than the average human — it’s a mind-boggling example of efficiency in packing, all on a microscopic scale.

“The work has ordered the sequenced pieces of axolotl genomic DNA sequence in the correct order, as it is on the chromosome,” Elly Tanaka, a biochemist at the Vienna BioCenter’s Institute of Molecular Pathology who also works on axolotl genetics but is unaffiliated with the research, said in an email. “This is important because, in all animals with vertebrae, genes are turned on and off by control sequences that are actually lying pretty far away from the gene itself.” The research, she added, will be important for seeing if the ability to regenerate could ever be activated in humans.

A wild axolotl in a conservation lab in Mexico City in 2014. (Photo: RONALDO SCHEMIDT/AFP via Getty Images, Getty Images)
A wild axolotl in a conservation lab in Mexico City in 2014. (Photo: RONALDO SCHEMIDT/AFP via Getty Images, Getty Images)

How the genes fold is important in figuring out how the axolotl grows its initial bits and pieces and then what sequences are kicked into second gear when any one of those components needs replacing. To figure out the locations of different DNA strands, the team made different proteins in the animal fluoresce, highlighting the loci of interest.

“There are a lot of details involved with regenerating a limb,” Smith said. “We’re not only now thinking about the genome as a linear structure, but also the higher orders of 3D structures that it takes on.”

Today, there are populations of axolotls kept at various research institutions, not to mention the animals sold in pet shops. But captive populations suffer from inbreeding, and the number of wild animals, which exclusively inhabit the waters of and surrounding Lake Xochimilco in Mexico City, are dwindling. “They’re endangered in their native habitat,” Smith said. “We should be considering that this is a real species that lives in a real habitat.”

Conservation and genetic inquiry are obviously not in opposition, but if we want to continue learning about and eventually benefitting from this species’ superpowers, we should make sure the wild population continues to survive and thrive.

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