Jan 26, 2018

Scientists sequence the genome of a regenerating salamander

The Mexican axolotl Ambystoma mexicanum is a model organism for regeneration research. Photo: IMP Vienna

The critically endangered Mexican axolotl can regenerate body parts better than practically any other vertebrate on the planet. If a limb is lost, a limb can be regrown.

"We need to figure out why and hopefully mimic that in humans," says Northeastern University's James Monaghan, who studies the biology of regeneration in the salamander species.

What's new: Scientists figured out a way to piece together the axolotl genome and this week reported a nearly complete sequence.

The programs of development that give us our forms in the womb shut down in humans as we grow — but axolotls and some other animals keep that ability forever.

For a long time, researchers have tried to sequence the animal's genome in order to better understand how cells can know what was lost and what to regenerate. But the tiny salamander has a big genome — at 32 billion base pairs, it's ten times the size of the human genome — filled with lots of repetitive sequences that make it hard to sequence. It is like putting together a puzzle that has a lot of the same pieces, says Monaghan, who was not involved in the new work.

What they found:

  1. The salamander's genome may be 10 times larger than that of humans but it has only slightly more genes (about 23,000).
  2. It has 3 genes that birds, mammals and reptiles don't and that accumulate in the cells of regenerating limbs, though their role is unknown.
  3. Between the genes that encode proteins are long stretches of DNA. (Most species have them, including us but in not nearly the same abundance as axolotls.) In earlier work, researchers found some of these DNA elements are activated during regeneration.
"Now we can say this particular gene turns on only during regeneration and what drives it. It gives us access to the regulatory elements, which are key pieces of the puzzle to understanding regeneration."
— James Monaghan, a biologist at Northeastern University says about the new genome sequence

It goes beyond limbs. The salamander species can also regenerate their ovaries, lungs, brain, heart, spinal cord and parts of their retina. Little is known about how their internal organs can regrow. The next step is to figure out whether they use the same pathways, Monaghan says.

One more thing: The researchers found the axolotl's developmentally important genes aren't as big as their other genes. "There has been selection to keep them small," says Monaghan. It is speculation at this point but it could be so they can be transcribed quickly when needed — say, during regeneration.

Go deeper: Sam Schipani at Smithsonian on the effort to save the axolotl in the wild.

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