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Comment by Ericson2314 | Hacker News Reader

> Most importantly, viruses and bacteria innately "want" to spread. Prions do not have any biological mechanism for their own propagation - they are just an unfortunate mistake of nature. And this seems to be key why there has never been a massive prion outbreak.

I disagree here, and but it's not fatal to your argument. Anything that reliably reproduces "wants" to. Hell, I bet prions can evolve too on large enough time scales (heterogeneous induced refolding), so we can say they are alive. But sometimes the tortoise is too patient and the race ends before the hare tires.

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The prions are not involved in the formation of new proteins, so it's very^100 difficult that they can evolve to create more efficient versions. [I try to not use "impossible" because life finds a way ...]

Virus instead use their own material as the original to make copies, so any new good or bad variation will be copied in the offspring, and they can evolve.

In order to evolve there has to be some kind of genetic information passed on to descendants. But for prions there is no such mechanism. A lower energy state is assumed and that's that.

So prions are simply a result of entropy? Am I understanding that correctly?

All evolutionary change (and life itself) is due a combination of differences of entropy (aka an energy gradient existing), combined with randomness in the current environment allowing mutation/change and hence selection pressure.

I would say life is an artifact of non-erodicity. Rare things that self-replicate are over-abundant in hindsight.

There does not have to be genetic information for evolution.

Evolution only requires "descent with modification". DNA is a mechanism for this, but it is not necessarily the only one.

And prions don't have descent with modification. It's a regular mammal brain protein that got accidentally constructed backwards. There's nothing to pass on, nothing to modify.

Err, I think I remember a couple pretty famous articles that contradicts that prions generally don't have descent with modification, which may be what the person above us is referring to:

https://pubmed.ncbi.nlm.nih.gov/20044542/

https://pubmed.ncbi.nlm.nih.gov/17142317/

That's really neat. Still there should be a limited number of possible variants right? Like the energy landscape is fixed and will only admit so many possibilities?

FWIW Wikipedia says:

> Prion replication is subject to epimutation and natural selection just as for other forms of replication, and their structure varies slightly between species.[19]

[19] is https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848070

descent without modification sounds pretty hard to achieve for all but the simplest things.

This got me wondering: what is the advantage of genetic information (DNA / RNA) over a self-replicating entity without those convenient molecules?

My impression is that DNA / RNA-based organisms have a high tolerance for changes to their DNA / RNA, such that many genetic changes won't cause them to lose their self-replicating ability. This is great for evolution.

Prions, on the other hand, seem like they would have a low reproductive tolerance for changes to their structure.

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