Tibetans were able to adapt
to high altitudes thanks to a gene picked up when their ancestors mated with a
species of human they helped push to extinction, according to a new report by
University of California, Berkeley, scientists.
An unusual variant of a gene
involved in regulating the body's production of hemoglobin – the molecule that
carries oxygen in the blood – became widespread in Tibetans after they moved
onto the high-altitude plateau several thousand years ago. This variant allowed
them to survive despite low oxygen levels at elevations of 15,000 feet or more,
whereas most people develop thick blood at high altitudes, leading to
cardiovascular problems.
"We have very clear
evidence that this version of the gene came from Denisovans," a mysterious
human relative that went extinct 40,000-50,000 years ago, around the same time
as the more well-known Neanderthals, under pressure from modern humans, said
principal author Rasmus Nielsen, UC Berkeley professor of integrative biology.
"This shows very clearly and directly that humans evolved and adapted to
new environments by getting their genes from another species."
This is the first time a gene
from another species of human has been shown unequivocally to have helped
modern humans adapt to their environment, he said.
Nielsen and his colleagues at
BGI-Shenzhen in China will report their findings online July 2 in advance of
publication in the journal Nature.
The gene, called EPAS1, is activated
when oxygen levels in the blood drop, triggering production of more hemoglobin.
The gene has been referred to as the superathlete gene because at low
elevations, some variants of it help athletes quickly boost hemoglobin and thus
the oxygen-carrying capacity of their blood, upping endurance. At high
altitude, however, the common variants of the gene boost hemoglobin and its
carrier, red blood cells, too much, increasing the thickness of the blood and
leading to hypertension and heart attacks as well as low-birth-weight babies
and increased infant mortality. The variant or allele found in Tibetans raises
hemoglobin and red blood cell levels only slightly at high elevation, avoiding
the side-effects seen in most people who relocate to elevations above 13,000
feet.
"We found part of the
EPAS1 gene in Tibetans is almost identical to the gene in Denisovans and very
different from all other humans," Nielsen said. "We can do a
statistical analysis to show that this must have come from Denisovans. There is
no other way of explaining the data."
Harsh conditions on Tibetan
plateau
The researchers first
reported the prevalence of a high-altitude version of EPAS1 in Tibetans in
2010, based on sequencing of the genomes of numerous Han Chinese and Tibetans.
Nielsen and his colleagues argued that this was the result of natural selection
to adapt to about 40 percent lower oxygen levels on the Tibetan plateau. That
is, people without the variant died before reproducing at a much higher rate
than those with it. About 87 percent of Tibetans now have the high-altitude
version, compared to only 9 percent of Han Chinese, who have the same common
ancestor as Tibetans.
Nielsen and his colleagues
subsequently sequenced the EPAS1 gene in an additional 40 Tibetans and 40 Han
Chinese. The data revealed that the high-altitude variant of EPAS1 is so
unusual that it could only have come from Denisovans. Aside from its low
frequency in Han Chinese, it occurs in no other known humans, not even
Melanesians, whose genomes are nearly 5 percent Denisovan. A high quality
sequence of the Denisovan genome was published in 2012.
Nielsen sketched out a
possible scenario leading to this result: modern humans coming out of Africa
interbred with Denisovan populations in Eurasia as they passed through that area
into China, and their descendants still retain a small percentage – perhaps 0.1
percent – Denisovan DNA. The group that invaded China eventually split, with
one population moving into Tibet and the other, now known as Han Chinese,
dominating the lower elevations.
He and his colleagues are
analyzing other genomes to pin down the time of Denisovan interbreeding, which
probably happened over a rather short period of time.
"There might be many
other species from which we also got DNA, but we don't know because we don't
have the genomes," Nielsen said. "The only reason we can say that
this bit of DNA is Denisovan is because of this lucky accident of sequencing
DNA from a little bone found in a cave in Siberia. We found the Denisovan
species at the DNA level, but how many other species are out there that we
haven't sequenced?"
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