Genes Have Evolved to Minimize Translation Errors

New research suggests that the major detrimental effect of some mutations, especially in long-lived cells such as neurons, is the accumulation of toxic, misfolded proteins. This conclusion is at odds with the conventional understanding that the damage caused by mutations is linked to the loss of functional proteins.

Many protein molecules must fold into a precise three-dimensional configuration to become biologically active, and mistakes arising from mutation can cause misfolding, which can be toxic. For example, misfolded proteins are known to accumulate in neurons and are critically linked to fatal disorders such as amyotrophic lateral sclerosis (ALS). Yet, research would suggest that mistakes due to mutations arise in nearly 20% of the molecules produced by any given cell. To understand how genes evolve, it is necessary to understand how they adapt to this rather slipshod behavior.

In the current study investigators at the University of Texas (Austin, USA) and Harvard University (Cambridge, MA, USA) performed gene analysis of organisms as diverse as humans, mice, fruit flies, worms, yeast, and Escherichia coli. They reported in the July 25, 2008, edition of the journal Cell that natural selection has fostered the evolution of genes that minimize the effects of errors in translation such as misfolding.

"It has long been believed that the main force of natural selection on protein-coding genes is the need to maintain a working protein,” explained senior author Dr. Alan Drummond, a Bauer Fellow in the FAS center for systems biology at Harvard University. "Our work suggests that another force may be equally important: the need to avoid misfolded proteins resulting from errors in translation.”


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