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University of Chicago study overturns conventional theory in evolution

mutation rate of nonsynonymous changes (Ka) the rate of those mutations that do affect protein structure. These mutations are typically subject to natural selection. A nonsynonymous mutation will get accepted into or bounced out of the population based upon how the change alters protein function.

The researchers then studied the Ka/Ks ratio. A low Ka/Ks ratio indicates strong selection; conversely, a high ratio, weak selection. Some genes have a ratio of 0, which means protein changes are not accepted. It is, in a sense, "perfect."

For a pseudogene a stretch of DNA sequence that resembles a gene but has no function its Ka/Ks ratio is approximately 1.0, which means that synonymous and nonsynonymous mutations are accepted at the same rate since the gene is functionally irrelevant.

For a gene that is highly functional and important for the organism, its Ka/Ks ratio is typically low. For example, if a gene has a Ka/Ks ratio of 0.1, it means that it's highly selective and is only accepting 10 percent of the nonsynonymous mutations.

Regardless of the rate of new mutations at a particular gene, scientists have always presumed the percentage of nonsynonymous mutations accepted during evolution remains constant.

"This theory has been the workhorse of molecular evolution," Lahn said. "Thousands of scientific papers have been published based directly or indirectly on this notion."

The new data show that if more mutations show up at a gene, that gene tends to accept a higher percentage of those mutations.

"A gene under strong mutational pressure succumbs to that pressure," Lahn said. "For genes that have a high mutation rate, somehow selection appears to become less stringent."

Lahn cannot explain the mechanism of his findings and expects many will question this novel finding. "It's too radical," he said. "People just don't want to believe it, but the data are there."

"Lahn and his associates have foun
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Contact: Catherine Gianaro
catherine.gianaro@uchospitals.edu
773-702-6241
University of Chicago Medical Center
7-Jun-2005


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