Muck and Mystery
   Loitering With Intent
blog - at - crumbtrail.org
December 31, 2009
Quasi-Species

This isn't news, or surprising when the mechanics are grasped, but adaptation isn't an attribute unique to selfish genes.

"On the face of it, you have exactly the same process of mutation and adaptive change in prions as you see in viruses," said Charles Weissmann, M.D., Ph.D., the head of Scripps Florida's Department of Infectology, who led the study. "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 for the process of evolution."

Infectious prions (short for proteinaceous infectious particles) are associated with some 20 different diseases in humans and animals, including mad cow disease and a rare human form, Creutzfeldt-Jakob disease. All these diseases are untreatable and eventually fatal. Prions, which are composed solely of protein, are classified by distinct strains, originally characterized by their incubation time and the disease they cause. Prions have the ability to reproduce, despite the fact that they contain no nucleic acid genome.

Mammalian cells normally produce cellular prion protein or PrPC. During infection, abnormal or misfolded protein – known as PrPSc – converts the normal host prion protein into its toxic form by changing its conformation or shape. The end-stage consists of large assemblies (polymers) of these misfolded proteins, which cause massive tissue and cell damage.

"It was generally thought that once cellular prion protein was converted into the abnormal form, there was no further change," Weissmann said. "But there have been hints that something was happening. When you transmit prions from sheep to mice, they become more virulent over time. Now we know that the abnormal prions replicate, and create variants, perhaps at a low level initially. But once they are transferred to a new host, natural selection will eventually choose the more virulent and aggressive variants." . . .

The idea was first conceived by Manfred Eigen, a German biophysicist who won the Nobel Prize in Chemistry in 1967. Basically stated, a quasi-species is a complex, self-perpetuating population of diverse and related entities that act as a whole. It was Weissmann, however, who provided the first confirmation of the theory through the study of a particular bacteriophage – a virus that infects bacteria – while he was director of the Institut für Molekularbiologie in Zürich, Switzerland.

"The proof of the quasi-species concept is a discovery we made over 30 years ago," he said. "We found that an RNA virus population, which was thought to have only one sequence, was constantly creating mutations and eliminating the unfavorable ones. In these quasi-populations, much like we have now found in prions, you begin with a single particle, but it becomes very heterogeneous as it grows into a larger population."

There are some unknown dynamics at work in the prion population that leads to this increased heterogeneity, Weissmann added, that still need to be explored.

"It's amusing that something we did 30 years has come back to us," he said. "But we know that mutation and natural selection occur in living organisms and now we know that they also occur in a non-living organism. I suppose anything that can't do that wouldn't stand much of a chance of survival."

I once put it:
Anything that happens once will happen repeatedly. Anything that happens repeatedly will happen variably. The model we should be using is the ecosphere not a single human mind. The fundamental rule of ecology is diversity - if there is more than one way to make a living there will be many ways livings are made. Anything that works will change. Nothing is constant, the field and the players are in flux, there is no equilibrium, no stasis, no durability. There is resilience.

There is also deceit. Anything that can be built can be hacked. Anything that has value will be counterfeited. Every trust will be broken, every identity will be spoofed. Every entity will have predators. Everything will get its fair share of abuse.

Living or not.

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Comments

I don't quite follow this logic, I must be missing something. For the Prion fold to evolve in this way, there must be some advantage that is exploited, and I can't see why virulence is a trait that is necessarily an advantage. In most disease causing entities, the reverse is observed, a tendency to evolve to be less lethal.

This presumably relates to the method of transmission from animal to animal, something that folds more readily i can imagine being useful, but unless that improves the transmission, how could it be said to 'evolve' ? BTW, is the mechanism of transport from one animal to another in, say, Scrapie, known ?

Posted by: Ed Snack at January 1, 2010 12:14 AM

I understood them to be saying that the ability to convert normal PrPC to PrPSc evolves, this would be the virulence part, and that resistance to swainsonine increased with exposure, another sort of evolution.

Transmission from animal to animal is like an infectious disease. The PrPSc prions are hardy and can exist in soil for years, so the animals do not have to have direct contact with one another.

The press release is brief and not perfectly clear. I can see your points though I had a different take.

Posted by: back40 at January 1, 2010 09:45 AM
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