Evolutionary Origins Of Prion Disease Gene Uncovered

[steven johnson]

There has been a confusion of how life started. There is the RNA school which notes that because RNA can reporduce on its won, perform the tasks of DNA and enzymes, it is thought to have once been capable of independent life as seen in some RNA viruses. But there is another school of theories about the first life forms, the "peptide first" hypothesis. In this scenerio, rudimentary peptide-based creatures may have been infected by RNA and mutated. Peptides of up to 55 amino acids can be synthesized abiologically on mineral surfaces. The story goes that the first step of template based self replication may have been the infection of self-assembling peptide metabolism by abiologically synthesized RNA molecules which were incapable of template based self replication. The coevolution of the RNA and peptides may have then evolved into 'life'.

Prions similarly have the ability to auto-catalytically irreveribly changing the conformation of host encoded protein into the prionic form> Prion propogation ("replication") has been described as a sequence of repetative cycles of aggregate "shearing" into smaller seeds followed by the growth of these seeds into full sized polymers. Prions are found in other ortanism including yeast and fungi and apparently perform biological function. The feeling is that these prions are a very old biochemical structures that are inherited in a non-Mendelian manner. Prions are possibly a relic of an early stage of peptide evolution. They are highly resistant to UV and ionizing radiation, the environment present on the early earth during the start of life. The thought is that self-assembling peptides occured before polynucleotides, on the earth, with prions being one of the relics of early stage peptide evolution.

An interesting hypothesis that prions may mimic a very ancient analogical code of biological tranmission rather than a digital one seen with nucleic acids.


http://www.dermato-santacasa.com.br/artigos/are_prions_related_to_the_emergence_of_early_life.pdf

A University of Toronto-led team has uncovered the evolutionary ancestry of the prion gene, which may reveal new understandings of how the prion protein causes diseases such as bovine spongiform encephalopathy (BSE), also known as "mad cow disease."

Diseased prion proteins are responsible for the fatal neurodegenerative Creutzfeldt-Jakob disease (CJD) in humans, and BSE, scrapie and chronic wasting disease (CWD) in livestock. Overall, this work holds promise for efforts to reveal the physiological function of members of the prion protein family and may provide insights into the origins and underlying constraints of the conformational changes associated with prion diseases. The study was published on September 28, 2009, in the online journal PLoS ONE.

The team's analysis suggests that the prion gene is descended from the more ancient ZIP family of metal ion transporters. Members of the ZIP protein family are well known for their ability to transport zinc and other metals across cell membranes.

The U of T laboratory initially demonstrated the physical proximity of two metal ion transporters, ZIP6 and ZIP10, to mammalian prion proteins in living cells. As with the normal cellular prion protein, ZIP6 and ZIP10 exhibit widespread expression in biological tissues with high transcript levels in the brain. Schmitt-Ulms then made the startling discovery that prion and ZIP proteins contain extensive stretches of similar amino acid sequence. The researchers next documented that the respective segments within ZIP and prion proteins are computationally predicted to acquire a highly similar three-dimensional structure. Finally, the team uncovered multiple additional commonalities between ZIP and prion proteins which led them to conclude these molecules are evolutionarily related.




Evolutionary Origins Of Prion Disease Gene Uncovered

[trotsky]

1. Fascintating news.

Good to hear they are making progress learning about these diseases.

[Deep13]

2. Wow.

Hereditary conditions seem to be so much more complex than simply DNA. I saw a show one Nova a couple weeks ago on epigenetics, anothwer fascinating field of study.