Big difference?
Changes in the regulatory region of a single gene may have had a profound affect on human evolution.

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Did More Endorphins Make Us Human?

Humans and chimpanzees share at least 98% of their DNA, yet chimps are an endangered species while people have used their superior cognition to transform the face of the Earth. What makes the difference? A new study suggests that evolutionary changes in the regulation of a gene implicated in perception, behavior, and memory may be partly responsible.

Thirty years ago, geneticist Mary-Claire King and biochemist Allan Wilson proposed that changes in how genes are regulated, rather than in the proteins they code for, could explain important differences between chimps and humans (Science, 11 April 1975, p. 107). To test this hypothesis, an international team led by evolutionary biologist Gregory Wray of Duke University in Durham, North Carolina, focused on the gene that codes for the protein prodynorphin (PDYN), a precursor to a number of endorphins, opiatelike molecules involved in learning, the experience of pain, and social attachment and bonding. Humans carry one to four copies of a region of DNA that controls the expression of this gene. The functional differences triggered by the number of copies and other variations in the segment are unknown, although some variants have been linked to schizophrenia, cocaine addiction, and epilepsy.

Wray and his colleagues sequenced this regulatory region and some flanking DNA from 74 human chromosomes as well as 32 chromosomes from seven other primates, including chimps, gorillas, and orangutans. As the team reports in the December issue of PloS Biology, none of the nonhuman primates had more than one copy of the region. In addition, all human copies had five DNA mutations not seen in the other primates, and the human segment induced a 20% greater expression of the PDYN gene than did the chimp segment. The team concludes that the pattern is a solid example of natural selection acting on the human lineage after it split from the chimp line from 5 million to 7 million years ago.

The Gray team's work "speaks directly to King and Wilson's hypothesis," says molecular biologist Sean Carroll of the University of Wisconsin, Madison. Evolutionary geneticist Bruce Lahn of the University of Chicago says that the work is one of the first human examples of selection acting on a regulatory element and adds to a short list of brain genes favored during the evolution of humans. But he and others note that it is not yet clear what mental or behavioral traits were favored by selection. "It is a bit early to say that these changes were key to what makes us human," Lahn says. "But it seems like a reasonable hypothesis."

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