If they can replicate imperfectly, they're subject that evolutionary processes.

They don't replicate. Prions can't themselves make more prions like viruses do.

I think the main difference is an imperfectly-replicated virus or bacteria might still be viable.

A prion only makes itself. Even if it replicated imperfectly, the odds of a slightly different misfolded protein becoming another prion are vanishingly small (otherwise we'd all be dead) because there probably just are very, very few configurations possible. The vast majority of misfolded proteins just do nothing.

There are several billion humans who are each replicating millions of copies of each of the 20,000 or so proteins during their lifetimes. It seems pretty unlikely that there are many misfolds that haven't occurred. It's just that only a handful become prions. And even if they do, prions are thankfully very hard to communicate (again, we'd all be dead if they weren't).

They can induce correctly-folded proteins to misfold, effectively replicating.

But shouldn't the number of misfolds be very limited or just one so that evolution cannot occur? It almost sounds like fearing that fire will evolve.

> fearing that fire will evolve.

Well now I have new nightmares... :)

But in seriousness, I don't know much, but I believe that protein-folding is a hugely complicated problem that still lies at the edge of our understanding, therefore I conclude that we can't really conclude that the options for a replicating, harmful prion are basically harmless.

I mean...we don't even really know how common prions are, right? We only have noticed a handful because they have dramatically bad symptoms. A large number of replicating but harmless prions could exist (right?).

Obviously there's no reason to panic, but considered caution and study seems a better reaction than overconfident dismissal.

I don't know how many conformation changes could plausibly be caused by a prion or how many of them would be stable (and I'd imagine it depends heavily on the protein), but the number of possible conformations is incredibly large for any reasonably large protein.

Viruses can't replicate themselves either. Cells replicate viruses. And prions replicate by deforming healthy proteins.

Whether that replication can be incorrect and produce a different kind of prion, I don't know. If it can, evolution will do its work.

Not exactly. Presumably almost all imperfect replications lead to dead ends (or we'd all be dead). Also, because they transmit poorly from host to host, even if one did evolve, which might be impossible, it'd probably die when it's host did.

Given that each human replicates each protein many millions of times over the course of their life, and that there have been several billion humans alive, if that were possible we'd probably have experienced it by now and again all be dead.

With the same effect I can argue that viruses and bacteria are just misarranged RNA :)

I think this underestimates the complexity of proteins.