The genome of the immortal jellyfish has been sequenced
by B. David Zarley  /  September 4, 2022

“The immortal jellyfish is, true to its name, biologically immortal, capable of reversing its life cycle to perpetually begin again.  When the jellies’ adult forms — called medusa — are stressed, injured, or otherwise in an unideal situation, they revert back to an earlier stage of their life cycle, becoming a film of cells that looks for a place to anchor and develop into a polyp. From there, new medusae bud off of it, allowing the immortal jellyfish to reproduce asexually and be reborn.

“Stages of Turritopsis dohrnii rejuvenation: from medusa (1),
regressing to a cyst (4), which becomes an asexual polyp (7)”

And unlike most other jellies that have reset abilities limited to before becoming sexually mature, the immortal jellyfish can do it even after it reproduces sexually as an adult, giving it two different avenues of reproduction. Insofar as we know, the immortal jellyfish can do this an unlimited number of times — hence the name. (Note, however, that it is called immortal, not invincible; they can still totally die. The fate of everything in the ocean generally is to be eaten at some point,” as Monty Graham, director of the Florida Institute of Oceanography, pointed out to the Wall Street Journal.)

Now, researchers at Spain’s University of Oviedo have sequenced the immortal jellyfish’s genome, providing clues about how it Edge of Tomorrow’s itself. For their study, published in PNAS, the researchers sequenced the jellies’ genome at various stages in its life cycle. Then they compared the sequenced genome of this smaller-than-a-pinky-nail jelly to the related — but, alas, merely as mortal as the rest of us — crimson jelly to tease out genetic differences which may account for the immortal jellyfish’s ability.

“If there was a genetic change during the reversal, it would be important,” María Pascual-Torner, an Oviedo marine biologist and study co-author, told El País. In fact, there were multiple changes in the immortal jellyfish genome that make it superior at copying and repairing its DNA then lesser, time-bound creatures. It has twice as many copies of a gene called GLI3, which plays a role in stem cell’s ability to become other cells, El País reported.

The immortal jellyfish also does a better job of maintaining the protective caps on the end of its chromosomes, called telomeres. In other species, including humans, telomeres have been shown to shorten with age. “What makes this animal special is the synergy of all these changes, which make this jellyfish rejuvenate,” Pascual-Torner said. “The most interesting thing is that it’s not a single molecular pathway…It is a combination of many of them,” Jan Karlseder, a molecular biologist at the Salk Institute unaffiliated with the study, told the WSJ.

“If we want to look for an extension of healthspan, we cannot just focus on one pathway. That will not be sufficient. We need to look at many of them and how they synergize.” Don’t expect these insights to unlock our own immortality or wind up in a miracle cosmetic; the work is more about helping us to better understand the basic mechanisms of aging, with an extreme example. “We can’t look at it as, hey, we are going to harvest these jellyfish and turn it into a skin cream,” Graham told Reuters. “It’s one of those papers that I do think will open up a door to a new line of study that’s worth pursuing.”

“The immortal jellyfish reverts to a juvenile stage when starved”

Immortal jellyfish genes identified that may explain their long lives
by Jason P. Dinh  /  8/29/22

“An immortal species of jellyfish has double copies of genes that protect and repair DNA. The finding could provide clues to human ageing and age-related conditions. Jellyfish start their lives as drifting larvae. They eventually attach to the seafloor and develop into sprout-like polyps. The bottom-dwellers clone themselves, forming stacked, sedentary colonies that bud off into free-swimming umbrella-shaped medusas. That stage is a dead end for most jellyfish – but the immortal jellyfish (Turritopsis dohrniican reverse the cycle.

When times get tough, like in harsh environments or after injury, they melt their bodies into amorphous cysts, reattach to the seafloor and regress into polyps. They can restart the cycle indefinitely to skirt death by old age. To find out how the immortal jellyfish staves off aging, Maria Pascual-Torner at the University of Oviedo in Spain and her colleagues sequenced its genome – its full set of genetic instructions – and compared it to that of the related but mortal crimson jellyfish (Turritopsis rubra).

They found the immortal jellyfish had twice as many copies of genes associated with DNA repair and protection. These duplicates could produce greater amounts of protective and restorative proteins. The jellyfish also had unique mutations that stunted cell division and prevented telomeres – chromosomes’ protective caps – from deteriorating. Then, to pinpoint how T. dohrnii reverts into polyp form, the scientists looked at which genes were active during this reverse metamorphosis.

They found the jellies silenced developmental genes to return cells to a primordial state and activated other genes that allow the nascent cells to re-specialise once a new medusa buds off. Together, Pascual-Torner says, these genetic alterations shield the animal from the weathering of time. But Maria Pia Miglietta at Texas A&M University at Galveston points out that the crimson jellyfish can also rejuvenate, just not as commonly as T. dohrnii.

Using them for comparison might reveal differences in the degree of immortality rather than the key to immortality itself, she says. Still, Pascual-Torner says the genes they identified could be relevant to human ageing. They could inspire regenerative medicine or provide insights into age-related diseases like cancer and neurodegeneration. “The next step is to explore these gene variants in mice or in humans,” she says.”

Journal reference: Proceedings of the National Academy of SciencesDOI: 10.1073/pnas.2118763119 



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