Enlarged spleen key to diving endurance of Indonesian 'sea nomads'

Competitive breath-hold divers have only two options to increase their time underwater - through training, they can try to boost their lung capacity or increase their red blood cell count.

Over hundreds if not thousands of years, however, a group of Southeast Asian "sea nomads" known for their deep-diving prowess has evolved a better solution: larger spleens.

The spleen holds oxygenated red blood cells, so presumably an enlarged spleen - those of the sea nomads, or Bajau people, are about 50 percent larger than the spleens of unrelated, non-diving neighboring groups - injects more blood cells into the circulation and makes more oxygen available for basic body functions during prolonged dives.

The physical and genetic changes that have enabled the Bajau to dive longer and deeper is yet another example of the immense variety of human adaption to extreme environments, in this case, environments with low levels of oxygen, said Rasmus Nielsen, a professor of integrative biology at the University of California, Berkeley. These examples can be key to understanding human physiology and human genetics.

"We can't really make experiments in humans, where we expose people to new conditions and have controlled genetic experiments in the same way we can do in fruit flies and mice," Nielsen said. "But nature has made experiments for us that tell us how humans react and adapt genetically to a whole new set of physiological conditions, so that we can explore and learn much more about the interaction between genetics and physiology."

The surprise finding led researchers from the University of Copenhagen and UC Berkeley to a genetic mutation that appears to have spread throughout the population to increase spleen size. This genetic variant upregulates thyroid hormone, which in mice has been linked to larger spleen size.

A second genetic adaptation associated with the Indonesian population of Bajau involves the constriction of blood vessels in the extremities to preserve oxygen for vital organs, a key part of the human "diving reflex."

Nielsen and Eske Willerslev, who is on the faculty of both the University of Copenhagen in Denmark and the University of Cambridge in the U.K., are the senior authors of a paper about the finding that will be published online April 19 in the journal Cell. The first author is Melissa Ilardo, a doctoral candidate at the University of Copenhagen.

Sea nomads

The Bajau people, groups of whom are spread among the islands of Indonesia, Malaysia and the Philippines, are often called sea nomads, and traditionally lived on boats and harvested nearly everything they ate from the sea. Some have been shown to spend as much as 60 percent of their work day diving for food - spearing fish and octopus and gathering crustaceans and sea cucumbers - at depths greater than 70 meters, or 230 feet, using only a wooden mask. Linguistic analysis suggests that they have lived this way for more than a thousand years. A chronicler of one of Ferdinand Magellan's voyages recorded their unusual lifestyle in 1521.

Ilardo was intrigued by the Bajau (be joe') and proposed a Ph.D. thesis project to find out whether and how they adapted to sustained deep dives. She suspected this involved the spleen, since contraction of the spleen is a key part of the mammalian diving reflex, and some deep-diving seals, such as the Weddell, have enlarged spleens.

"The closest thing to the Bajau in terms of underwater working time is sea otters; they are also spending about 60 percent of their time in the water," Ilardo said. "That is really remarkable, even compared to other professional or traditional divers. They are just spending an extraordinarily long time underwater compared to their recovery time."

Studies suggest that the Bajau experience the most extreme low-oxygen situations humans encounter.

Willerslev, Ilardo's adviser, connected her with Nielsen, who has investigated how humans living in low-oxygen environments adapt and how that's reflected in their genetic heritage. In 2014, for example, Nielsen showed that Tibetans adapted to living at oxygen-poor high altitudes by selecting for a specific genetic mutation that prevented chronic high red blood cell levels, which can cause medical problems. Though both Willerslev and Nielsen were dubious about the success of Ilardo's project, they supported the idea of testing it out.

In 2015, Ilardo visited one Bajau community living on an island connected via a bridge to the bigger island of Sulawesi. The village, Jaya Bakti, provides easy access to the ocean for often weeks-long excursions during which the Bajau live off the fruits of the sea. The community seemed eager to learn about their genetic heritage, so she returned twice that year with a portable ultrasound machine to measure spleen size in 59 Bajau in addition to 34 people from a neighboring village, Koyoan, inhabited by the unrelated Saluan people, who do not dive.

After eliminating individuals who were related, she analyzed the data and found that, on average, the Bajau had spleens about 50 percent larger than those of Saluans. According to Nielsen, this means they could mobilize perhaps 10 percent more red blood cells during a dive than those not adapted to the low-oxygen conditions of breath-hold diving. There was no difference in spleen size between Bajau who dived and Bajau who did not dive.

"The Bajau have a different solution to low-oxygen conditions than the Tibetans," Nielsen said. "While it is unhealthy to have high concentrations of red blood cells all the time, it is really good for you if you have high RBCs when you really need them. They have increased the storage capacity in the spleen for when they need it, but they don't have any negative effects of constantly having too high red blood cells."

Diving reflex

Contraction of the spleen to release oxygenated red blood cells into the circulation is a key part of humans' and all mammals' innate diving reflex, which is initiated when you hold your breath and at the same time immerse your face in cold water.

"We all know that if you dive down into cold water, you feel refreshed," Nielsen said. "That is not just in your brain, it's in your body. In addition to contraction of the spleen, you also have bradycardia, a lowering of the heart rate, and the blood is shunted into the central vital organs and away from the skin."

Ilardo also collected spit samples from the Bajau villagers and identified several gene variants that were at much higher frequency in the genomes of the Bajau versus the Saluans. One, PDE10A, codes for an enzyme called phosphodiesterase, which mediates contraction of smooth muscle but is also associated with thyroid hormone release. The researchers collaborated with a group in the Netherlands, which confirmed that higher PDE10A levels are associated with an increased release of thyroid hormone.

"We think the way it works is that the expression of this variant gene changes thyroid hormone release, which then has an effect on spleen size," Nielsen said. "Nothing is really known about the genetic basis of spleen size in humans, so it is hard to validate without further research."

Ilardo, who has now taken up a postdoctoral position at the University of Utah, plans to pursue the connection between these genetic variants, spleen size and diving ability, while the Dutch group is looking at the connection between thyroid hormone levels and spleen size in humans and possible medical implications.

"This really tells us how valuable and important indigenous populations are around the world that are living extreme lifestyles, in terms of understanding the function of various genetic traits and finding the underlying genetic background for various physiological traits," said Willerslev, who is a pioneer in analyzing the genomes of early humans and indigenous populations. "Most of these populations are completely understudied, and I think there is a huge benefit, not only potentially to them, but also to the rest of mankind by actually paying some attention to them."

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The work was supported by the Lundbeck Foundation, Danish National Research Foundation, Danish National Science Foundation and KU2016.

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