Wednesday, February 15, 2012

Disease-causing prions have evolutionary benefits

Prions are usually associated with mad cow disease, or creutzfeldt-jakob disease. They are proteins gone bad, which aggregate in places where they shouldn't, such as the brain. They have changed their appearance resulting in loss of their original function. Because their capability to reproduce and aggregate is harmful, it usually causes the patient to die. However, scientists have shown that prion formation may actually benefit an organism in harsh conditions. It is thought to be an important evolutionary process to create the much-needed diversity to survive challenging environments as a species.

Scientists from the Whitehead Institute in Cambridge studied the model organism yeast, to find out what happens when a certain protein turns into a prion. Yeast uses a protein called sup35 for 'quality control' in the production of other proteins. They are made by reading the correct lines of DNA, which is performed by specialized cellular machinery and specific forms of DNA that function as intermediate messengers. Without sup35, the machines start churning out aberrant forms of protein. Normally, sup35 dictates how to read the DNA, but without it, this form of quality control is lost.
Transcription: 'reading' the DNA by forming intermediates (mRNA). Translation: turning the intermediates into protein by machines called ribosomes.
Normally, making a different form of protein than what the DNA dictates is not quite a good thing. However, when yeast finds itself in challenging conditions it is worthwhile to try to come up with a new form of protein that could ameliorate the struggle for existence. What the scientists found is that yeast with the prion state enabled was able to withstand challenging conditions set up in the lab quite well, while yeast colonies that were unable to form prions mostly died.

When things go bad, organisms often try desperate things to stay alive. Turning sup35 into a prion is yet another example, but it is probably the first time turning a protein into its disease-causing shape is shown to have evolutionary benefit. It is striking that the formation of prions caused yeast to develop all sorts of new traits when subjected to harsh living conditions. They did not show up in colonies that were unable to form prions.

Even more striking, perhaps, is that these characteristics became heritable, despite the DNA remaining intact. This is because the prions result in epigenetic changes, which are adaptations that influence the activity of the DNA. Even though the code itself remains intact, these heritable characteristics affect whether cellular machinery can 'read' what's on the genome. It is likely the first time that prions have been shown to function as epigenetic agents. 

Our newfound knowledge about the prion state of proteins does not help us much. However, it is an interesting mechanism that may explain where prions come from. All we've seen so far is that a change in shape makes them cause disease and spread themselves throughout the body. Therefore, an evolutionary role is highly surprising.

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