Creature Feature: Axolotl

Imagine a creature with translucent skin, a headdress made of feathery membranes that it uses to breathe underwater, elusive in its natural habitat of subterranean or cavern pools.  Sounds like science fiction, but fact is often stranger than fantasy. The axolotl, Ambystoma mexicanum, is a species of salamander originating in the cenotes of southern Mexico and Latin America. This bizarre amphibian is believed to be nearly extinct in the wild, but lives on as a model organism in developmental biology labs across the world.

beautiful Mexico
You might find axolotls here, if they weren’t nearly extinct in the wild. [Source]
This month, the axolotl genome was published in Nature, unveiling some of the genetic secrets to its life history.  In celebration, here are some of the coolest attributes of these strange creatures.

1. Axolotls can regenerate almost any part of their body!

Axolotls can regenerate almost any body part, including their tail, limbs, jaws, and even spinal cord.  Sometimes axolotls go overboard, and will grow an extra limb in addition to the replacement, ending up with five limbs after a wound instead of the original four.  As if that wasn’t amazing enough, axolotls can do this seemingly limitlessly, replacing a single limb multiple times, over and over again.

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As in Monty Python, limb loss really is but a flesh wound for axolotls. On the right, an axolotl that grew two limbs in place of one. [Source 1, 2]
Axolotls are able to regenerate in this way by “de-differentiating” their cells at the site of the wound. This means that current differentiated cells, be they nerves or muscles, essentially have an identity crisis and are open to new possibilities of being a different type of cell.  In utero, mammals and most animals are full of pluripotent stem cells that can grow up to become part of any differentiated tissue type needed, such as neurons, endocrine glands, or skin cells.  While adult humans (and most other animals) have some stem cells in their tissues, these cells’ have limited ability to divide, making regeneration unfeasible.  Rather than rely on a limited stock of existing stem cells, axolotls are able to revert their cells at the wound back to the equivalent of embryonic stem cells, which can go on to become whatever tissue they need to regenerate.

Interestingly, the introns of developmental genes—the parts of a gene transcript that are not actually involved in making a protein—are much smaller in axolotls compared to humans, mice, and frogs. This makes their developmental genes shorter overall. The researchers hypothesized that this allows them to more easily make gene copies via transcription, which might facilitate quickly “re-developing” cells during regeneration.

2. Axolotls have a special developmental pathway, making them “forever young”:

Second to their regeneration abilities, axolotls also have another superpower: they can stay young indefinitely.  Axolotls exhibit neoteny, which means that like Peter Pan, they never really grow out of their salamander baby/larval stage.  While they might look like larva, they can still reproduce despite this superficial phenotypic resemblance to tadpoles. In other amphibians, reproduction can only occur after they have transitioned to the adult stage. The reason axolotls have evolved to stay young remains a evolutionary conundrum, but some hypotheses suggest that this strategy may allow axolotls to stay in a safe aquatic environment if transitioning to a terrestrial habitat is too risky. In a way, axolotls are reminiscent of millennials who stay in their childhood home because of the harsh perils of adult life and an unforgiving job market!

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A larval California southern long-toed salamander (left) compared to an adult axolotl (right). [Source 1, 2]
To facilitate this neotenic or extended infantile stage, axolotls have modified hormone systems compared to frogs and other amphibians.  Frog tadpoles begin their growth spurt by producing thyroid hormone, which allows them to grow legs and larger heads.  Axolotls retain the ability to respond to this hormone—they have receptors for it in their cells, and when injected with it, will metamorphose to a certain degree—but they do not naturally produce much of the hormone.  Just a simple reduction in their endocrine signaling is what allows them to stay “forever young”.

3. Axolotls have huge genomes:

The published genome of the axolotl consists of 32 gigabases, 10 times the size of the human genome! Generally, amphibians tend to have the largest genomes of all animals. Why so large? The jury is still out, but some hypothesize that the complex life cycle of amphibians, from an aquatic tadpole (complete with a tail) to an air-breathing, jumping frog, demands a larger genome to coordinate the metamorphosis between these very different forms.  However, this hypothesis assumes that genome size corresponds with functionality of the genome (i.e., most of those genes code for proteins that can actually be used by an animal), rather than just being old “junk” taking up space in the genomic garage.

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Amphibians have the largest genome sizes compared to all other animal taxa. [Source]
Interestingly, the amount of “junk” DNA animals hoard varies by species, and this does not seem to correlate with evolutionary history. Of the axolotl genome, 65.6 % of it is repeating sequences that do not end up coding for actual proteins in the animal.  The human genome is made up of 51% of such non-coding DNA, but other amphibians—like the famous Xenopus model frog—only have 37% non-coding DNA in their genome.

Now that the full axolotl genome has been sequenced, researchers can further to elucidate the genetic mechanisms underlying many of the highly-specialized adaptations in this fascinating amphibian…

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The recently-sequenced axolotl genome could reveal genetic underpinnings of regeneration! [Source]

[By: Victoria Farrar]


References:

Lévesque M. et al (2007) Transforming Growth Factor Beta Signalling Is Essential for Limb Regeneration in Axolotls. PLoS ONE 2(11) e1227.

Safi R. et al (2004) The axolotl (Ambystoma mexicanum), a neotenic amphibian, expresses functional thyroid hormone receptors. Endocrinology, 145(2).

Nowoshilow, N. et al (2018) The axolotl genome and the evolution of key tissue formation regulators. Nature 2018 Jan 24.

Main featured image [Source, John Clare 2012]

 

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