Friday, April 27, 2012

Evolution, redefined

If you're reading a biology blog, you're probably aware that Charles Darwin was an important dude, and not just for discovering the plant hormone auxin. He also published the theory of evolution, completely revolutionizing our understanding of the world. However, not until the discovery of DNA and genes was it clear how exactly certain physiological traits could be passed from parent to offspring, and how new traits could emerge through mutations. Now, however, disease-causing particles called prions might be redefining what evolution is and how it works.

Prions are proteins that are usually produced in the human body, but for some reason get misfolded and form aggregates which cause brain tissue to deteriorate. The best-known prion diseases are Mad Cow, Creutzfeld-Jakob, scrapie, and kuru, but there's a prion disease affecting nearly every mammal. Prion diseases are passed by ingesting prion particles. When the normal protein encounters the misfolded prion form, it gets converted into the prion form as well. It's still unclear how exactly this happens, or what causes a previously normal protein to be misfolded into a prion. However, it was previously well-accepted that this prion form was unchangeable. Researchers at Scripps decided to challenge this idea based on a puzzling piece of evidence

They noticed that when you infect mice with a sheep prion, it becomes more virulent over time. An initial spike in virulence from the sheep-to-mouse transfer may have made sense, because it would simply indicate that the mouse brain is more susceptible than the sheep's, but if the prion disease starts killing faster as it infects more mice, this indicates it is adapting to its host to become more successful. So, they decided to test that idea by exposing prions to different conditions and selective pressures, to see if certain variants were more prominent in one situation versus another.

Sure enough, researchers found that different prion particles were present in brain cells versus cell cultures, and that they could get the predominant type to switch if they transferred prions from brain to culture or culture to brain. Also, they exposed prion-infected cells to swainsonine, a compound previously found to have prion-control properties, and found that a drug-resistant form of the prion quickly became the major component of the population. Removing swainsonine returned the population to being mostly susceptible, with less than 1% resistant prions.

The head of the study, Dr. Weissmann, thinks this will have important treatment applications. Because they thought prions couldn't mutate and evolve, the key was going to be finding some way to target the prion and leave the normal, non-problematic cell protein alone. But, if prions can evolve, it's likely that any treatment blocking or removing prions is going to quickly become ineffective, because prion particles resistant to it will quickly take over the population. Instead, Weissmann thinks we should be focusing on finding ways to remove the normal protein from cells, because without a normal protein to convert, the prions will be unable to form large aggregates and cause problems.

Regardless how prion treatments end up looking, it is highly interesting that our ideas of evolution have, once again, expanded. We've been incorrect about a lot of accepted ideas about evolution, for example "silent" mutations. Silent mutations are when there's a mutation, but it doesn't change the protein's building blocks at all, so the rationale was that there was no way that could affect fitness if the protein was the same. However, it turns out that some codes for building blocks are preferable and faster for an organism to make than others, and faster protein assembly may be an advantage. Now, it turns out we might be wrong that the only way a mutation can be passed on is through genetic material, because prions can evolve to fit their environmental conditions better and can pass this along to other members of the population despite being only protein.

1 comment:

  1. 1. Way to slip auxin in there
    2. Prions scare the bejesus out of me and this doesn't help... brain is definitely off the menu