"Contrary to what was believed, our work shows that even in the human genome, codons are positioned to minimize errors," says Wilke, assistant professor of integrative biology at Texas. "Just like a mistake on your taxes is more costly than a mistake on your grocery list -- so you concentrate more on your taxes -- cells seem to concentrate on preventing mistakes that might result in costly misfolded proteins."
Drummond and Wilke analyzed humans, mice, fruit flies, worms, yeast and E. coli bacteria and discovered that all of these organisms have evolved ways to prevent the production of costly aberrant proteins.
"Finding such sweeping effects from a single, simple cost has the potential to reshape the way evolution is studied at the molecular level," Drummond says. "While much work has focused on how evolution makes creatures different, our work emphasizes fundamental ways in which all life is the same."
While evolutionary studies are often retrospective, Drummond and Wilke also developed a molecular-level evolutionary simulation, allowing them to track the evolution of genomes encoding many simple proteins over millions of generations. In some simulations, they added evolutionary costs for misfolded proteins, while in others this cost was not factored in. They found that genomes evolving with misfolding costs developed all the genome-wide patterns seen in real organisms, while those evolving without costs did not.
The work could have long-term implications for our understanding of neurodegenerative diseases. Misfolded proteins are known to accumulate in neurons and are central players in fatal disorders such as amyotrophic lateral sclerosis, better known as Lou Gehrig's disease. Drummond and Wilke suggest that mistranslation may contribute to long-studied forms of ALS and other similar diseases.
Wilke says the current study may lead to better ways to detect genes
|Contact: Steve Bradt|