Genetics of Korea's extreme divers could unlock chronic disease treatments
Now, an international team of researchers has found evidence of natural selection at work: a genetic variation found in Jeju Islanders that helps to keep their blood pressure from rising as much when diving, according to a paper published in the journal Cell Reports.
In theory, understanding the genetic adaptation could lead to the development of medications that help people at risk for stroke or blood pressure problems.
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'When you're diving, your blood vessels are responding in complicated ways to try to keep your vital organs safe as your oxygen is running low,' explained Melissa Ilardo, assistant professor of biomedical informatics at the University of Utah Health, who led the study.
'It becomes a trade-off between short term and long term benefits - what keeps you safe while you're diving might lead to complications further down the line. Evolution seems to have found a way to balance this out - a genetic variant that may protect divers while they're holding their breath and beyond.'
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In their study, researchers discovered two kinds of adaptation at work.
The first, developed over centuries, affects part of the genetic blueprint of all Jeju Islanders whether or not they dive, providing a protective blood pressure response to immersion in water. The variant is also thought to protect pregnant women who dive from developing preeclampsia, a complication of pregnancy that can be serious, even fatal.
The other adaptation, present only in the Haenyeo, is gained from training and causes the heart rate to slow when the women dive.
'When you're diving, every heartbeat is bringing more oxygen to your cells which is normally a good thing,' Ilardo said, 'but when you don't have oxygen coming in, you want to slow that down.'
Although it has not been established definitively, the history of diving and the genetic adaptation might be the reason Jeju Islanders have one of the lowest age-standardized stroke death rates in South Korea: a little over 24 deaths per 100,000 people; the rate in the United States is about 37 deaths per 100,000 people.
The Haenyeo are not the only diving population scientists have studied. Ilardo and others have examined the male and female Bajau divers of Indonesia who have evolved larger spleens, which may help them hold their breath longer underwater. Other scientists have investigated Tibetans, who have evolved with the ability to live at higher altitudes where there is less oxygen.
Insights gained from examining small populations with unique characteristics have helped researchers develop treatments for various medical conditions. The class of medications called PCSK9 inhibitors, used to lower LDL (bad) cholesterol, were discovered when research teams studied a French family with the genetic condition familial hypercholesterolemia, which affects about one in 300 people worldwide.
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Ilardo said it is not clear why the Jeju Island divers are all women, 'but at some point, we think, it switched from men and women diving, which we see in many places in the world, to all women.'
In the course of her work on the Haenyeo, Ilardo made three trips to Jeju Island and collaborated with another scientist, Joo-Young Lee, from Seoul National University, who has spent years with the divers and earned their trust.
'I mean it's mind-blowing, especially given the average of age of the divers,' Ilardo said. 'I watched an 87-year-old woman jump off a boat that hadn't stopped moving.'
Although generations of Haenyeo dove into the icy waters wearing only cotton bodysuits, around the 1980s, they began wearing wetsuits.
The scientists compared three groups of about 30 women each: Haenyeo; non-Haenyeo Jeju Islanders; and non-Haenyeo women from the South Korean mainland. The authors acknowledged the study was limited by its relatively small sample size.
Researchers measured physiological characteristics, such as blood pressure and heart rate, then sequenced the DNA of participants to look for genetic differences.
In a simulated dive, ordinary Jeju Islanders' heartbeats slowed by about 20 beats per minute, researchers found, about the same amount as women on the South Korean mainland. In the same circumstances, the Haenyeo, who have been diving their whole lives, slow their heartbeats by up to twice that number.
In simulated dives, participants held their breath and submerged their faces in a basin of cold water, which triggers the same response in the body as diving. The simulation allowed the researchers to carry out the study without having untrained, and possibly non-swimming, older women try to dive in the open ocean.
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The genetic variant shared by Jeju Islanders, not just the Haenyeo, triggers the protective blood pressure response to immersion in water, but it's not entirely clear how it works. The variant appears to influence a receptor that plays a role in blood vessel inflammation.
Ilardo and her colleagues validated their findings by searching the large-scale All of Us database, run by the National Institutes of Health, for people with the same genetic variant. They found that among people of European ancestry, the same variant was linked to the protective blood pressure response seen in the Jeju Islanders, though the effect was not as strong.
The scientists think that natural selection for this genetic variation started about 1,200 years ago.
The process, they say, may have unfolded like this:
Two pregnant Jeju Island women were diving many years ago. One of them carried the protective genetic variant while the other did not. Over the course of her pregnancy, the woman without the protective variant developed preeclampsia because of her daily diving; the condition led to the deaths of mother and child.
The woman with the protective variant survived and so did her children.
Even the loss of a few children per generation adds up over time. Gradually, more and more Jeju Island children are born with the variant.
Tatum Simonson, associate professor of medicine at UC San Diego Health, called the study, which she was not involved in, 'a good first step towards understanding how genetic adaptation, but also importantly, how training can have an effect on blood pressure in these sort of extreme conditions.'
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Simonson cautioned that working with blood pressure measurements can be challenging. Human blood pressure is a snapshot in time that reflects what is going on in a person's life at that moment. It will be different if a person is anxious, excited, angry, or depressed. To their credit, she said, the scientists collected multiple blood pressure readings at different points.
Ilardo collaborated on the research with a team of physiologists led by Nikolai Nordsborg at the University of Copenhagen.
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