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Key brain regulatory gene shows evolution in humans

y; Matthew Rockman of Princeton University; Matthew Hahn of Indiana University; Nicole Soranzo of University College London; and Fritz Zimprich of the Medical University of Vienna in Austria. The research was sponsored by the National Science Foundation and NASA.

"We focused on the prodynorphin gene because it has been shown to play a central role in so many interesting processes in the brain," said Wray. "These include a person's sense of how well they feel about themselves, their memory and their perception of pain. And it's known that people who don't make enough of prodynorphin are vulnerable to drug addiction, schizophrenia, bipolar disorders and a form of epilepsy. So, we reasoned that humans might uniquely need to make more of this substance, perhaps because our brains are bigger, or because they function differently.

"Also importantly, the part of the gene that produces the prodynorphin protein shows no variation within humans, or even between humans and any of the great apes," said Wray, who is a professor of biology. "So, if we found any variation in this gene due to evolution, it was likely to be in its regulation. And our premise is that the easiest way to generate evolutionary change is to alter regulation."

In their studies, the researchers analyzed the sequence structure of the PDYN promoter segment in humans and in seven species of non-human primates -- chimpanzees, bonobos, gorillas, orangutans, baboons, pig-tailed macaques and rhesus monkeys. They found significant mutational changes in the regulatory sequence leading to humans that indicated preservation due to positive evolutionary selection. They also found an "evolution-by-association," in which sequences near the regulatory segment showed greater mutational change -- as if they were "dragged along" with the evolving regulatory sequence.

In contrast, the researchers found that the DNA segment that coded for the PDYN protein itself -- as well as other sites spread
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Contact: Dennis Meredith
919-681-8054
Duke University
12-Dec-2005


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