DNA Clues to Our Kind: Regulatory gene linked to human evolution

A gene that exerts wide-ranging effects on the brain works harder in people than it does in chimpanzees and other nonhuman primates, a DNA disparity that apparently contributed to the evolution of Homo sapiens, according to a new study.

The gene participates in production of prodynorphin, an opiumlike protein that serves as a building block for chemical messengers in the brain known as endorphins. Studies have implicated endorphins in the anticipation and experience of pain, in the formation of intimate emotional bonds with others, and in learning and memory.

All primates possess a virtually identical prodynorphin gene, say geneticist Matthew V. Rockman of Princeton University and his colleagues. However, a separate stretch of DNA regulates the extent to which the gene generates prodynorphin. This regulatory DNA displays a handful of mutations in people that must have evolved by natural selection and aided human survival, the scientists propose. The new findings appear in the December PLoS Biology.

“This is the first documented instance of a neural gene that has had its regulation shaped by natural selection during human origins,” says geneticist and study coauthor Matthew W. Hahn of Indiana University in Bloomington.

Rockman’s team first compared chemical sequences of prodynorphin-regulating DNA from 74 people and 32 nonhuman primates. The latter group consisted mainly of chimps but included gorillas, orangutans, baboons, and macaque monkeys.

The people generally possessed two to four copies of the regulatory sequence, in contrast to just one copy for each nonhuman primate. Moreover, the people displayed distinctive rearrangements at five spots along the DNA sequence. A strikingly large proportion of the regulatory sequence—about 10 percent—differed between people and chimps, Hahn says.

Rockman and his coworkers also inserted copies of human and chimp regulatory sequences into human-brain cells grown in laboratory cultures. Chemical stimulation of neurons containing the human sequence yielded much more prodynorphin than did stimulation of cells containing the chimp sequence.

Finally, the scientists analyzed DNA from 510 individuals around the globe. They found that many people now living in Europe and eastern Africa possess three copies of the prodynorphin regulatory sequence, whereas people in India and China usually possess two copies of that sequence.

Changes, or mutations, in the human prodynorphin regulatory sequence must have enhanced survival over other primate species, the investigators contend, while the geographic differences that they found may have bestowed as yet unknown advantages on specific human populations. The prodynorphin-regulating gene may indeed have contributed to the evolution of people, says geneticist Sarah Tishkoff of the University of Maryland at College Park.

Geneticist Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, regards the new study as the first convincing demonstration of a regulatory gene influencing human evolution. Until now, such evidence has been “notoriously hard to find,” he says.

Mutations of regulatory and protein-making genes acted in concert during human evolution (SN: 9/3/05, p. 147: Chimps to People: Apes show contrasts in genetic makeup), Pääbo holds. However he adds that it’s unclear whether geographic patterns of duplication in this regulatory sequence arose through natural selection.