One way to study evolution at the molecular level is to examine changes of when and where proteins are expressed in the body. "But there are many challenges to study the evolution of protein expression. Instead, we chose to track structural changes in proteins," said graduate student Eric Vallender, lead author of the article along with former graduate student Steve Dorus, both of Lahn's laboratory.

Researchers examined the DNA of 214 genes involved in brain development and function in four species: humans, macaques (an Old World monkey), rats and mice. (Primates split from rodents about 80 million years ago; humans split from macaques 20 million to 25 million years ago; and rats split from mice 16 million to 23 million years ago.)

For each of these brain-related genes, they identified changes that altered the structure of the resulting protein, as well as those that did not affect protein structure. Only those genetic changes that alter protein structure are likely to be subject to evolutionary selection, Lahn said. Changes in the gene that do not alter the protein indicate the overall mutation rate the background of random mutations from which evolutionary changes arise, known as the gene's molecular clock. The ratio of the two types of changes gives a measure of the pressure of natural selection driving the evolution of the gene.

Researchers found that brain-related genes evolved much faster in humans and macaques than in rats and mice. Additionally, the human lineage has a higher rate of protein changes than the macaque lineage. Similarly, the human lineage has a higher rate than the chimpanzee lineage.

"For brain-related genes, the amount of evolution in the lineage leading to humans is far greater than the other species we have examined," Lahn said. "This is based on an extensive set of genes."

They argue that a significant fraction of genes in the human genome were impacted by this selective process
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Contact: Catherine Gianaro
catherine.gianaro@uchospitals.edu
773-702-6241
University of Chicago Medical Center
28-Dec-2004