'Perception' gene tracked humanity's evolution, scientists say

November 14, 2005

A gene thought to influence perception and susceptibility to drug dependence is expressed more readily in human beings than in other primates, and this difference coincides with the evolution of our species, say scientists at Indiana University Bloomington and three other academic institutions. Their report appears in the December issue of Public Library of Science Biology.

The gene encodes prodynorphin, an opium-like protein implicated in the anticipation and experience of pain, social attachment and bonding, as well as learning and memory.

"Humans have the ability to turn on this gene more easily and more intensely than other primates," said IU Bloomington computational biologist Matthew Hahn, who did the brunt of the population genetics work for the paper. "Given its function, we believe regulation of this gene was likely important in the evolution of modern humans' mental capacity."

Prodynorphin is a precursor molecule of the neurotransmitters alpha-endorphin, dynorphin A, and dynorphin B, collectively called opioids because their action is similar to stimulatory effects caused by the drug opium.

The notion that humans are more perceptive than other primates would hardly be news. But the list of genes known to have tracked or guided humanity's separation from the other apes is a short one. Genes controlling the development of the brain almost always turn out to be identical or nearly so in chimpanzees and human beings. And as it turns out, the protein prodynorphin is identical in humans and chimps.

It's the prodynorphin gene's promoter sequence -- upstream DNA that controls how much of the protein is expressed -- where the big differences are. "Only about 1 to 1.5 percent of our DNA differs from chimpanzees," Hahn said. "We found that in a stretch of DNA about 68 base pairs in length upstream of prodynorphin, 10 percent of the sequence was different between us and chimps."

Hahn said this "evolutionary burst" is responsible for differences in gene expression rates. When induced, the human prodynorphin gene was 20 percent more active than the chimpanzee prodynorphin gene. Past research has also observed variation in expression levels within humans.

This report supports a growing consensus among evolutionary anthropologists that hominid divergence from the other great apes was fueled not by the origin of new genes, but by the quickening (or slowing) of the expression of existing genes.

Hahn and his colleagues at Duke University, University College London and Medical University of Vienna first became interested in primate prodynorphin after noticing an unusual amount of variation in the human version's promoter. The scientists decided to examine the prodynorphin gene in human beings around the world and in non-human primates to see whether such variation was commonplace and whether that variation affected gene expression.

The group found a surprisingly large amount of genetic variation among humans within the prodynorphin gene's promoter. They examined prodynorphin genes from Chinese, Papua New Guineans, (Asian) Indians, Ethiopians, Cameroonians, Austrians and Italians.

The group also sequenced and cloned prodynorphin genes from chimpanzees, gorillas, orangutans, rhesus macaques, pigtail macaques and guinea baboons. The researchers found that high genetic variation in the prodynorphin promoter was unique to humans. Other primates' promoters were far more homogeneous.

Exactly how prodynorphin influences human perception is unknown. Evidence for its various effects comes entirely from clinical studies of people who have mutations in the gene. Past clinical studies have also indicated a positive correlation between lower prodynorphin levels in the brain and susceptibility to cocaine dependence.

Matthew Rockman, David Goldstein and Gregory Wray (Duke University); Nicole Soranzo (University College London); and Fritz Zimprich (Medical University of Vienna) also contributed to the research. It was funded by grants from the National Science Foundation, NASA, the Royal Society, and the Leverhulme Trust (U.K.).
-end-
To speak with Hahn, please contact David Bricker.

Indiana University

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