Remove p21 Gene = Grow new limbs like lizards tail | Hacker News Reader

Remove p21 Gene = Grow new limbs like lizards tail

physorg.com

22 pointskeltecp1112 comments

Article slightly overhyped. Title should be "Single gene finally pinpointed as source of unusual regenerative powers of MRL mice". They can't regenerate limbs, but they can regrow heart sections, ear holes, fingers, etc.

http://www.fightaging.org/archives/2010/03/regeneration-in-m...

The MRL breed existed for a while (created for another purpose) before their regenerative powers were noticed. Similarly, the p21-knockout breed used to confirm the findings here also existed for years, and no-one noticed they could regrow ear tissues without scarring, etc. Makes you wonder what else exists in the hundreds of common lab breeds.

Anyway, the significance of this is that from a single gene, researchers can now walk through the list of biochemical mechanisms that gene pertains to, and perhaps more quickly answer the questions:

a) do mammals still have all the necessary machinery to regenerate like salamanders? b) can it be activated easily?

My gut feel on the bigger picture is that evolution ditched regeneration in favor of cancer suppression in mammals - though mice are not a good example of that process in action, being pretty much cancer factories in comparison to other mammalian species. If you look at p21, it's central to all sorts of stem cell related and cancer suppression mechanisms. It's surprising and unknown as to why p21-knockout mice are so normal, frankly.

Cancer, embryonic development, and blastema-style regrowth in adult creatures all look quite similar in many ways. A heavy duty anti-cancer mechanism and regrowth of tissues in adults may just not be terribly compatible from an evolutionary perspective. Which isn't they aren't compatible from a biotech perspective; many small single or few gene changes that produce favorable outcomes have not been selected for, but demonstrated in the lab to increase mouse life span, boost cancer resistance, provide regenerative powers at little cost, and so forth.

So, does that make it a valid question what evolutionary advantage was gained by losing that gene ?

Perhaps none. It might be that the loss didn't result in a significant enough disadvantage to hinder the growth of the population without it. There are plenty of genetic traits that are not particularly adaptive: chance, too plays a role. The assumption that the genetically youngest populations are optimal is a kind of teleology, no?

Perhaps a large metabolic cost for larger animals- hard to maintain that energy cost when you've just had your limb cut off + trying to fight off infection, run away from predators, etc.

Having had a herpetologist roommate at one time, A large part of being a reptile, snakes in particular, involves sitting around and doing nothing.

Mammals seem to have a different take, always moving and scurrying. Perhaps it was not tenable?

Maybe I misread the article, but it sounded like having the gene could raise one's risk of cancer.

It could (particularly since p21's suppression is related to general anti-cancer processes), though they explicitly said they did not observe it in the mice trials (they were actively looking for cancer).

Mice have short lives. I am not sure how frequent cancer is in mice compared to humans.

If it increases the risk of cancer it might be infeasible for species with a long generation cycle. With a short generation cycle the cancers might not kill off too many individuals before they regenerate?

Wonder what happens if you split a limb?

It'll be just like earthworms. You can cut off your finger and plant it somewhere and create a clone of yourself.

It's cuz p21 regulates the cell cycle (mitosis). p21 is a CDK inhibitor. CDK is necessary for the cell cycle to proceed past "checkpoints". So when you have p21, you have CDK inhibitors, so cell division doesn't proceed. No p21 = less inhibition = more growth. (And unchecked growth is one main cause of tumors).

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