Genetic mutations could finally explain how Tibetans survive 'the roof of the world'

12 February 2018

Humans might be the most resilient species on Earth, but until recently, no one could explain how a small population survives the incredibly harsh conditions of the Tibetan Plateau – a lofty, oxygen-starved environment that towers 4.5 km above sea level.

Here, at the so-called ‘roof of the world’, there’s 40% less oxygen than at sea level and harmful ultraviolet (UV) radiation beams down at dangerously high levels. And yet scientists estimate that humans have been thriving in this region for millennia.

So how do they do it?

Researchers have investigated the DNA of high-altitude Tibetans to find the secrets hidden in their genetic make-up.

Thanks to the largest ever sample of genomes for this kind of study, it’s the first time we’ve had such a clear insight into how human biology can specialise to cope with harsh, high-altitude environments.

“Previous studies were based on sequencing on less than 100 people. This is the first time we were able to run a genetic study of thousands of Tibetan people,” Professor Jian Yang from The University of Queensland’s Institute for Molecular Bioscience (IMB) explained.

When the Tibetan people’s genomes were compared with those of non-Tibetans, nine genetic variants (or gene mutations) were identified as the potential key to their incredible survival skills.

And one of those variants has been linked to a long-extinct subspecies of human that once interbred with Homo sapiens.

Pinpointing survival traits

In 2016, Yang and his colleagues from IMB teamed up with researchers at the Wenzhou Medical University in China to compare the genomes of more than 3,000 Tibetans with 7,200 non-Tibetans of Eastern Asian ancestry.

Of the nine major differences they found, two could be linked to the way high-altitude Tibetans have acclimatised to the Plateau’s incredibly thin air – mutations in or near the genes EPAS1 and ELGN1.

The EPAS1 mutation plays a role in reducing haemoglobin in the blood, which makes it easier to pump oxygen around the body when there’s much less of it in the atmosphere.

This is the opposite of how mountain climbers’ bodies respond to high altitudes – haemoglobin production is temporarily increased to help distribute oxygen through the blood. But if left to function like this long-term, it could lead to deadly blood clots and a higher risk of stroke.

EPAS1 is thought to have been passed down by a mysterious subspecies of ancient human called the Denisovans, and Yang and his team found that its haemoglobin-lowering mutation has a frequency of 40 per cent in Tibetans, but almost 0 per cent in non-Tibetans.

They also found that a variant near the MTHFR gene might help with the damaging levels of UV rays on the Tibetan Plateau.

“Some studies report that with high UV radiation exposure, you have reduced folate production,” he said, which suggests that high-altitude Tibetans have developed this mutation to compensate for the degradation of folate due to high UV radiation.

Questions still unanswered

Despite the key insights provided by this extensive study, there are still many questions that have been left unanswered, in no small part because linking a specific gene to a single trait is an incredibly difficult thing to do.

“If a trait-associated genetic variant is located in a genomic region where there are multiple genes with any known function to do with that trait, it’s actually very difficult to know which gene is responsible for the association,” Yang said.

Researchers now need to carry out functional studies, which aim to understand how a genetic variant causes a difference in gene expression, and ultimately leads to a difference in observable phenotype (a set of physical characteristics or traits).

And while they discovered nine key genetic variants that set the Tibetan highlanders apart from the rest of the local population, Yang suspects this is just the beginning – we now need even larger samples of genomes to fully understand the extent of their unique adaptions.

"We believe this set of nine is not the total - there must be a lot of others.”

The study was published in Proceedings of the National Academy of Sciences.

Banner image credit: Streetflash/


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