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Key brain regulatory gene shows evolution in humans

e -- showed evidence of "negative selection" that would preserve their original structure.

A key experiment, said Wray, was a laboratory demonstration that such regulatory mutations did have functional significance. When the researchers cultured human neural cells with either the human or chimpanzee regulatory PDYN segments, they found that the human segments caused the cells to produce more PDYN neuropeptide.

"So, these experiments told us that those mutations that we flagged by a statistical method as being likely to be under selection actually do something important in terms of function," said Wray. "The human version increases expression of the gene and production of prodynorphin, which is the direction of change we predicted."

The researchers also found evidence of evolutionary selection when they compared the regulatory sequences in people from different populations -- including those from Cameroon, China, Ethiopia, India, Italy and Papua New Guinea. Those analyses showed higher differences among the individual populations, but reduced variation within them. Such a pattern is a signature of evolutionary selection acting on the genetic sequence, said Wray.

Still mysterious, he said, is how the prodynorphin gene changes affect human neural development.

"All we can conclude now is that this gene is a very strong candidate for having a functional role in human evolution, and that its role probably has something to do with cognition. But beyond that, it's very hard to make a clear argument about specifically what that role is.

"We do know that not making enough prodynorphin causes clinical problems, but we don't know what having more of it did for us humans. We're hoping the clinical psychiatrists and psychologists can give us more insight into that aspect."

Wray and his colleagues have already identified a collection of some 250 other candidate genes -- mainly those active in the brain -- that they are beginn
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Source:Duke University


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