"Lifeless" prions capable of evolution

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Scientists have shown for the first time that "lifeless" prion proteins, devoid of all genetic material, can evolve just like higher forms of life.

The Scripps Research Institute in the US says the prions can change to suit their environment and go on to develop drug resistance. Prions are associated with 20 different brain diseases in humans and animals. The scientists say their work suggests new approaches might be necessary to develop therapies for these diseases. In the study, published in the journal Science, the scientists transferred prion populations from brain cells to other cells in culture and observed the prions that adapted to the new cellular environment out-competed their brain-adapted counterparts. When returned to the brain cells, the brain-adapted prions again took over the population.

Charles Weissmann, head of Scripps Florida's department of infectology who led the study, said: "On the face of it, you have exactly the same process of mutation and adaptive change in prions as you see in viruses.

"This means that this pattern of Darwinian evolution appears to be universally active.

"In viruses, mutation is linked to changes in nucleic acid sequence that leads to resistance.

"Now, this adaptability has moved one level down- to prions and protein folding - and it's clear that you do not need nucleic acid (DNA or RNA) for the process of evolution."

The full is HERE.

Apparently, reproduction, variation and natural selection are all that bis necessary for evolution to take place.

How exactly does that work without DNA?

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@rosborne979,

maybe what it really is saying is that evolution hasnt been shown to "move down" to prions , but instead that the process of modification is a function of chains of peptide polymers.
Think about it, theyve been busy trying to establish the foundations of "life" from cell walls to mitochondria (all without t,m,r NA and DNA) and now we have an inkliong that the sequences that evolve are inherent in the simplest of these polymers

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These polymer proteins, how old are they? Maybe I should read the whole article....

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@farmerman,

How does a prion reproduce (make copies of itself)? I don't get it.

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@rosborne979,

The mechanisms proposed are varied and many not well understood. The "proteinaceous infectious particle" is what prion is short for and the mechanisms of the specific replication of these forms is still hazy.
It is known that prions are primarily a protein "chunk" that is unique to nerve cells and spinal cells in mammals. In humans nerve system prions are focused on the PrP gene (I got that from my handy dandy genome maps) , PrP is on chromosome 20 of humans.

Heres a clip from a Princeton (or just cadged by someone at the vir labs) microbio site

Quote:

The prion is a product of a human gene, termed the PrP gene, found on chromosome 20. This gene contains two exons separated by a single intron. Exon I and Exon II are transcribed and the two RNAs ligated into a single mRNA. This mRNA contains an open reading frame (ORF) or protein coding region which is translated into the PrP protein. The PrP protein is a precursor of the prion protein. It is termed PrP 33-35.

So, in English , its transcribed into a Messenger RNA segment from chromosome 20 . This gene from the #20 chromosome has two active attachment and transcription sites separated by an intron. The mRNA has an area that then transcribes the "proteinaceous receptor particle" which then transcribes into a prion.
NOW thats only one of a bazillion different means , and its as far as my trolley goes down understanding alley.The others are still being studied. If they are successful at cracking their means of transcription, wed have a successful means to treat a whole number of diseases not just KJ, but encephelitis, rabies, and several genetic cerebral diseases.

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@farmerman,

My understanding of the thinking as of a couple of years ago is that the protein does not actually replicate itself. What happens is the the PrP protein is normally present within the nervous system in it's normal conformation. However, aberrant folding of the polypeptide results in the protein that we care about. The abberantly folded molecule seems to be able to induce abnormal folding in previously normal PrP proteins that it comes in contact with, which in turn induce abnormal folding in its normal PrP neighbors, and so forth.

I've never heard mention of the error being made at the transcriptional level. I'd thought that the peptide sequence of the normal and abnormal proteins were identical.

**************

D'oh. Apparently I'm only thinking of "iatrogenic" (I think I'd go with "infectious" over "iatrogenic," meself) prion diseases -- e.g., mad cow and scrapie. Didn't know about these proteins' role in Alzheimers et al.

Looks to be a good overview here -- http://ghr.nlm.nih.gov/condition=priondisease --
which I'm going to look over more completely when I've got more time.

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@patiodog,

More poor skimming, re: their use of iatrogenic. Why cannot I read right?

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@patiodog,

Hey, Its Saturday and a holiday weekend, no pressures Pdog.

Happy New Year all.

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@farmerman,

Yeah, but I worked this mornin'. Sheesh.

Really hadn't known that this mechanism is at play in dementia and rabies, though I'd noticed that the plaques look similar on histological sections. Interesting.

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@patiodog,

patiodog wrote:

Yeah, but I worked this mornin'. Sheesh.

Really hadn't known that this mechanism is at play in dementia and rabies, though I'd noticed that the plaques look similar on histological sections. Interesting.

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@patiodog,

patiodog wrote:

Really hadn't known that this mechanism is at play in dementia and rabies, though I'd noticed that the plaques look similar on histological sections. Interesting.

I didn't either. Going to do some reading..

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@rosborne979,

rosborne979 wrote:

How does a prion reproduce (make copies of itself)? I don't get it.

I don't understand it either, but algorithms can and do follow natural selection rules once you let them run simulations on a supercomputer, or let them loose in the "wild". So how new is this discovery about prions? The link with mad cow disease, other dementias and Alzheimer's was made some time ago.

Quote:

The finding, which appears in the journal Nature, could explain one of the great mysteries in Alzheimer's disease: How components of the plaques that form in patient's brains are able to damage brain cells. It also could point the way to new treatments for the disease......"It's very exciting," says Lennart Mucke, director of the Gladstone Institute of Neurological Disease and a professor of neurology and neuroscience at the University of California, San Francisco. "The study shines the light on a very unexpected component."

http://www.npr.org/templates/story/story.php?storyId=101145687

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@rosborne979,

Without claiming any knowledge at all about prions, i would point out to you that evolution is the process whereby new organisms arise as a result of natural selection, and the evolutionary process does not stipulate that DNA must be present.

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@rosborne979,

rosborne979 wrote:

Apparently, reproduction, variation and natural selection are all that bis necessary for evolution to take place.

True. That's basically how Computer viruses, chain mails, and urban legends do it -- although their "variation" steps do have some help from somewhat-conscious human morons.

rosborne979 wrote:

How exactly does that work without DNA?

Short answer: It doesn't.

Detailed answer: In terms of reproduction, you can think of prions as the evil twins of proteins. Each prion is encoded in a string of DNA that also encodes a biochemically functional protein. As with proteins, the lives of prions start when an enzyme called RNA polymerase copies their DNA string to an RNA string. In the next step, Ribosomes "read" this RNA string to assemble a one-dimensional chain of amino acids. (Each triplet of RNA bases corresponds to one amino acid in this chain.)

Up to this step, the assembly of the one dimensional amino acid chain, proteins and prions are identical. It is only after this step that their biochemical pathways diverge: Some amino acid chains fold into a three-dimensional structure that can function within the bodies they're made for. These are the ones we call "proteins". Others fold into different 3d structures, which are useless for the body at best and harmful to it at worst. These are the ones we call "prions".

Bottom line: The Weisman quote you enthusiastically bold-faced is severely misleading. Because prions are essentially mis-folded proteins, they emphatically do need DNA to reproduce. The true story still fascinates, but it's more complicated and less spectacular: Because the genes for proteins receive some of their adaptive pressure through the prions that they also produce, anti-prion medications may have catastrophic side effects: DNA mutations that make prions resistant to the medication may also produce dysfunctional "legitimate" proteins. We ought to be very cautious about this as we develop anti-prion medications.

I suspect that Weisman fumbled an attempt to condense this fairly complicated issue into a media-friendly talking point -- off-the-cuff in an interview to boot.

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@Thomas,

Ugh -- I should have read the full BBC article before posting. His point is different. I'll be back.

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@Setanta,

Setanta wrote:

Without claiming any knowledge at all about prions, i would point out to you that evolution is the process whereby new organisms arise as a result of natural selection, and the evolutionary process does not stipulate that DNA must be present.

That's true, but I didn't know you could have biological reproduction without xNA of some type. I think the three basic components you need for evolution are: Reproduction, Variation and Selection.

I still don't understand how these prions reproduce. Thomas seemed to try to explain it, but then he retracted his post. I remain confused.

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@rosborne979,

I like Thomas's labeling of protein vs. prion (though prions are, biochemically speaking, proteins). The properly-folded protein functions normally. The prion (or improperly folded protein), does not function normally, and in some instances (for instance, in Kuru, Creutzfeld-Jacob disease, chronic wasting disease, and so forth) causes the properly-folded protein to refold itself like a prion. It's as if you could unbend a paper clip, put it next to another paper clip, and the former paper clip would cause the latter paper clip to become unbent, too.

Now, as to the point of the article, I think I'm understanding what it's getting at, but I'll have to take a better read...

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@patiodog,

I don't think he's talking about evolution in the strict biological dogma sense of the word, but rather as it pertains to complex adaptive systems (as High Seas has alluded to). If you consider the original infective prion to be generation one, all neighboring converted proteins were generation two, and so forth, I think what they're saying is that there is an increase in virulence over succeeding generations and in different environments, which suggests that there is some amount off variation in the re/mis-folding of proteins to prions.

1 Reply

@patiodog,

patiodog wrote:

I don't think he's talking about evolution in the strict biological dogma sense of the word, but rather as it pertains to complex adaptive systems (as High Seas has alluded to). ....

Thank you - for the record, not only I but Thomas and many others have mentioned non-living entities like algorithms or microscopic molecular swarms (at some point there was a book, though whether called The Swarm or something else I can't now recall, but it was by the same author as "Andromeda Strain"). Natural selection works in mathematical functions, crystalline structures and any number of other inanimate entities - and if there's a typo in my text, pls allow for tiny screen.

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@High Seas,

I thought you'd mentioned it first. I read some Pinker on the subject, but I think I lost track of the book about halfway through...

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"Lifeless" prions capable of evolution

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