Axolotl, worm genomes offer clues to regeneration

Axolotls and planarian worms don’t share all that much in common, except a robust ability to regenerate lost tissue. The successful assembling of whole genomes for both species, reported in the journal Nature, may help scientists discover which genes are involved in this process.

One thing the amphibian and the worm certainly don’t share is genome size. A team led by Elly Tanaka of the Research Institute of Molecular Pathology in Vienna, Austria, discovered that the axolotl (Ambystoma mexicanum) possesses the largest genome so far, coming in at 32 billion bases. (Humans have about three billion.)

The genome of the planarian worm (Schmidtea mediterranea) comprises just 800 million bases. It was fully assembled by a team led by Jochen Christian Rink, also of the Max Plank Institute.

And while the ability of axolotls to regrow missing limbs is impressive, planarian worms, hydra-like, can regenerate into multiple copies if they are chopped up into very tiny pieces. This process is driven by abundant pluripotent adult stem cells, called neoblasts. The cells are so potent than the introduction of just one into a worm that has received a lethal dose of radiation will revive it.

The description of the genomes of both species may well eventually yield explanations about which genes govern regeneration, and already some clues – or, at least, perplexing evidence – has been uncovered.

Tanaka and her team note certain genes and microRNA sequences are especially active in the cells of limbs undergoing regeneration. Interestingly, however, a gene known as Pax3 that plays a critical role in embryonic tissue development in many species, including humans, is absent.

Rink’s team found that planarian worm is lacking 124 genes that are essential for development in humans and mice. Some of these operate to repair DNA and govern chromosome separation during cell division.

Both genomes contain a higher than average number of repeated sequences, which are known to be involved in stem cell activity and embryonic development. Some of these symptoms have previously been linked to regeneration in newts, and fresh research is now underway to see if they play a similar role in these two organisms.

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