Standing atop a mountain thousands of meters in the air is one of the harshest of environments human can experience. But according to a study published earlier this year by a group of Chinese scientists in the journal PLoS One, it's also a place where the mysteries of DNA may be solved. Although the building blocks of human biology take generations to change permanently, researchers are looking at how short-term functions contribute to the process. Their focus on gene expression, one such function, is particularly sharp.

"Virtually all human activities change gene expressions," says scientist Liang Yu, one of the study's authors working at BGI, a renowned genomics institute in Shenzhen, China."When a gene is expressed, most likely it will be translated into a corresponding protein." Proteins, explains Liang, are the worker bees of the body, and all have genetic blueprints that guide their actions."[It's like] a house being coded by a design," he says.

But unlike a blueprint that goes untouched after the house is built, gene expressions morph constantly due to external environments. "Some people will put on weight in the winter and lose it in the summer," Liang poses, as an example of this change in design. "Even light signals from different landscapes and vistas, entering our eyes, affecting our mood, will also change our gene expressions."

In extreme landscapes and activities such as scaling mountains, gene expression changes drastically in an effort to help the body adapt to high altitudes and low oxygen levels. "Some climbers may suffer from mountain sicknesses caused by maladaptation," says Liang, "[but] the exact reasons are unknown to us." His team's discovery could change this, paving the way for the development of better treatment strategies.

The BGI scientists' findings show that gene expressions in multiple climbers become more identical as they ascend. The root causes of maladaptation, Liang says, are most likely found in this period of flux. Monitoring changes in gene expression, he explains, is in essence a way to follow illnesses as they develop in real time on the mountain.

 And follow, Liang and his team did. Having set up a high altitude research lab eight years prior, they were already established climbers when they tackled Mount Xixiabangma alongside their test subjects. The group climbed in China's Tibet Autonomous Region for nearly a month, tracking three men and one woman of varying ages as they summited more than 8,000 meters. "The worst days for the climbers, including myself, were the days we climbed from the base camp up to the mountaintop and then back to the base camp," he recalls. "The air was really thin and the climbing very strenuous."

The scientists' subjects had the added challenge of being somewhat out of practice. "If the climbers had climbed above 3,000 meters prior to the study, their bodies would have undergone changes and it would take time for these to be undone," Liang explains. In his view, having their climbers go six months without exposure to major altitude change was a "scrupulous" decision. "[They were] from different places and had different lifestyles and other factors influencing their gene expressions," he says. "But when they came to the same place, [undergoing] plenty of exercise, their gene expressions tended to be more similar to each other."

The next step was pinpointing which genes were stressed most by the climb. Gene expressions revert back to normal once the climber is back on less rocky ground "unless he or she suffers from chronic mountain sicknesses," says Liang. Over the course of the study, he explains, "some inflammatory factors were found to be higher-than-normal. We may now develop new anti-inflammation drugs to remit their symptoms."

That move might be just one of many small – or rather, short – steps to long-term change.

Tech Bytes

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