Study: Genetic quirk may have helped humans survive killer smoke

Backyard barbecuing or sitting around a campfire in the summer, toasty hands and roasted chestnuts in the winter - in any season, people love a nice fire.

And in the smoke that those flames produce, scientists may have found a clue to the success of our species.

For prehistoric humans, including Neanderthals, fire was their technology, providing heat, light, and a means of making more foods digestible. But when they made those fires in caves, they would also inhale great quantities of smoke and its toxic chemicals.

According to a new study from Pennsylvania State University and Oregon State University, a genetic mutation may have given evolutionarily modern humans the advantage over Neanderthals by making them less vulnerable to smoke's toxic effects. This mutation is found in modern humans, but not Neanderthals or any other primates.

"If you think of what would be in a cave, it's really nasty," said Gary Perdew, a professor of agricultural sciences at Penn State. "The people most susceptible would be children," who might not live long enough to reproduce.

"If you were susceptible to lung toxicity, you would have lung infections, you would die," Perdew said.

The mutation is in the aryl hydrocarbon receptor gene, which binds molecules from the environment, as well as some produced in the body. The mutation slows down how quickly smoke toxins are received and processed in our bodies.

The researchers found this mutation was unique in evolutionarily modern humans by comparing DNA sequences from modern humans, Neanderthals, Denisovans (close relatives of Neanderthals), and non-human primates. They found the mutation in all modern humans, as well as a 45,000-year-old human, the oldest human so far sequenced.

"We searched through over a thousand human genomes, we even looked in bush people, and we could not find anyone who was like Neanderthal. The Neanderthal version never survived," said Perdew.

"We metabolize these compounds at a rate that helps us if you breathe a lot of smoke. It gave us the right level of metabolism over toxicity," Perdew said. The right level, because if we metabolize the toxins too quickly, like the Neanderthal receptor does, the secondary chemicals that accumulate from metabolism build up too quickly to be excreted before they do damage.

Perdew says that although the findings suggest the mutation gave modern humans an evolutionary advantage, the suggestion is not certain. Something else could have killed off the Neanderthals. The only way to test the mutation would be to insert copies of the human and Neanderthal genes in mice, and then test the effects of smoke inhalation on their health.

"That's years off," Perdew said. "It's a long road to get to there."

Rachel Carmody, an assistant professor of human evolutionary biology at Harvard University, called the study exciting. "For the derived version to have replaced the ancestral version in all populations suggests that it confers an important advantage," she said. But, she added, "pinning down what advantage that might be is difficult because the aryl hydrocarbon receptor has multiple biological roles."

The receptor "also binds a variety of plant-derived compounds and compounds produced by gut microbes," she wrote in an email, so changes in it could have been caused by something other than smoke.

Today, though humans still have this mutation, it does not get quite the workout it did, thanks to our far-better-ventilated living spaces. "The level of indoor pollution in any other venue beyond standing in front of your fire and breathing the smoke, we handle that very well," Perdew said.

cgilman@philly.com

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