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Various species' genes evolve to minimize protein production errors
Date:7/24/2008

CAMBRIDGE, Mass. -- Scientists at Harvard University and the University of Texas at Austin have found that genetic evolution is strongly shaped by genes' efforts to prevent or tolerate errors in protein production.

Their study also suggests that the cost of errors in protein production may lie in the malformed proteins themselves, rather than the loss of functional proteins. Misfolded proteins can build up in long-lived cells, like neurons, and cause neurodegenerative diseases.

The work, by D. Allan Drummond at Harvard and Claus O. Wilke at Texas, is described in the July 25 issue of the journal Cell.

"It has long been believed that the main force of natural selection on protein-coding genes is the need to maintain a working protein," says Drummond, a Bauer Fellow in Harvard's FAS Center for Systems Biology. "Our work suggests that another force may be equally important: the need to avoid misfolded proteins resulting from errors in translation."

Protein molecules must fold to become biologically active, and mistakes can cause misfolding, which can be toxic. Yet the protein-producing factories in our cells are estimated to make mistakes in 20 percent of the molecules they produce. Adaptations to this surprising sloppiness may be crucial in understanding the evolution of genes across species, from bacteria to humans, say Drummond and Wilke.

Essentially, they write, natural selection has fostered the evolution of genes that minimize the effects of errors in translation, the production of proteins from genetic templates in cells. An example is the careful placement of codons, which are sections of DNA that code for amino acids, the building blocks of proteins. Some codons translate more accurately, and previous research had suggested that high-fidelity codons are positioned at key locations in the genome, where a mistake might be harmful. These studies, however, had only considered fast-growing organisms like '/>"/>

Contact: Steve Bradt
steve_bradt@harvard.edu
617-496-8070
Harvard University
Source:Eurekalert

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