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2-step process filters evolution of genes of human and chimpanzee

netic variation called HapMap for their analysis, which compared human variations with the chimpanzee genome. They focused their analysis on the simplest and most common mutations, those that alter just one letter, a single base pair, of DNA.

DNA uses a three-letter code to designate the 20 types of amino acids that are strung together in specific order to create a protein. Some mutations alter just one letter of the code, replacing one link in a protein's amino-acid chain with a different amino acid. While some of those substitutions make only a moderate difference in a protein's structure or function, others have radical impact on its shape and performance.

Radical amino acid changes alter protein function. Most of those are deleterious and get removed, but "when a mutation is beneficial, we do not know whether they tend to be the radical or moderate kind of amino acid changes," Wu said. "Since beneficial changes are the ones that fuel evolution, we wanted to find out if these improvements are smooth or jerky."

When Wu and colleagues sorted these changes according to their evolutionary success, they found that radical changes were more harshly screenednegatively and positivelyby the forces of evolution.

When radical changes occurred, those mutations were far more likely to be eliminated by negative selection. But in rare cases, radical mutations escaped elimination by negative selection. Once they had established a beach head, occurring in as little as five percent of a population, these radical mutations tended to spread quickly throughout the species, their survival or reproductive advantage allowing them to gain ground over multiple generations.

"We found that both positive and negative selection are more effective on the same subset of radical amino acid changes," Wu said. "If changes from amino acid one to amino acid two are more likely to be deleterious, then some fraction of those very same cha
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Contact: John Easton
john.easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
5-Mar-2007


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