Interbreeding with our fellow hominins appears to
have helped humans survive harsh climates.
· MAY 31, 2016
Native Tibetans make use of
a gene derived from Denisovans to stay healthy at high altitudes.
·
By EMILY SINGER
TEXT SIZE
Early human history was a promiscuous affair.
As modern humans began to spread out
of Africa roughly 50,000 years ago, they encountered other species that looked
remarkably like them—the Neanderthals and Denisovans, two groups of archaic
humans that shared an ancestor with us roughly 600,000 years earlier. This
motley mix of humans coexisted in Europe for at least 2,500 years, and we now know
that they interbred, leaving a lasting legacy
in our DNA.
The DNA of non-Africans is made up of roughly 1 to 2 percent
Neanderthal DNA, and some Asian and Oceanic island populations have as much
as 6 percent Denisovan DNA.
Over the last few years, scientists have dug deeper
into the Neanderthal and Denisovan sections of our genomes and come to a
surprising conclusion. Certain Neanderthal and Denisovan genes seem to have
swept through the modern human population—one variant, for example, is present
in 70 percent of Europeans—suggesting that these genes brought great advantage
to their bearers and spread rapidly.
“In some spots of our genome, we are more
Neanderthal than human,” said Joshua Akey, a geneticist at the
University of Washington. “It seems pretty clear that at least some of the
sequences we inherited from archaic hominins were adaptive, that they helped us
survive and reproduce.”
But what, exactly, do these fragments of
Neanderthal and Denisovan DNA do? What survival advantage did they confer on
our ancestors? Scientists are starting to pick up hints. Some of these genes
are tied to our immune system, to our skin and hair, and perhaps to our
metabolism and tolerance for cold weather, all of which might have helped
emigrating humans survive in new lands.
“What allowed us to survive came from other species,” said Rasmus Nielsen, an evolutionary biologist
at the University of California, Berkeley. “It’s not just noise, it’s a very
important substantial part of who we are.
* * *
The Tibetan plateau is a vast stretch of
high-altitude real estate isolated by massive mountain ranges. The scant oxygen
at 14,000 feet—roughly 40 percent lower than the concentrations at sea
level—makes it a harsh environment. People who move there suffer higher rates
of miscarriage, blood clots, and stroke on account of the extra red blood cells
their bodies produce to feed oxygen-starved tissue.
Native Tibetans, however,
manage just fine. Despite the meager air, they don’t make as many red blood
cells as the rest of us would at those altitudes, which helps to protect their
health.
In 2010, scientists discovered that Tibetans owe
their tolerance of low oxygen levels in part to an unusual
variant in a gene known as EPAS1. About 90 percent of the Tibetan
population and a smattering of Han Chinese (who share a recent ancestor with
Tibetans) carry the high-altitude variant. But it’s completely absent from a
database of 1,000 human genomes from other populations.
The unique gene then flourished in those who lived at high altitudes and
faded away in descendants who colonized less harsh environments.
In 2014, Nielsen and colleagues found that Tibetans
or their ancestors likely acquired the unusual DNA sequence from Denisovans, a
group of early humans first described in 2010 that are more
closely related to Neanderthals than to us.
The unique gene then flourished in
those who lived at high altitudes and faded away in descendants who colonized
less harsh environments. “That’s one of the most clear-cut examples of how
[interbreeding] can lead to adaptation,” said Sriram Sankararaman, a geneticist and computer
scientist at the University of California, Los Angeles.
The idea that closely related species can benefit
from interbreeding, known in evolutionary terms as adaptive introgression, is
not a new one. As a species expands into a new territory, it grapples with a
whole new set of challenges—different climate, food, predators, and pathogens.
Species can adapt through traditional natural selection, in which spontaneous
mutations that happen to be helpful gradually spread through the population.
But such mutations strike rarely, making it a very slow process. A more
expedient option is to mate with species that have already adapted to the
region and co-opt some of their helpful DNA. (Species are traditionally defined
by their inability to mate with one another, but closely related
species often interbreed.)
This phenomenon has been well documented in a number of species, including mice that
adopted other species’ tolerance to pesticides and butterflies that
appropriated other species’ wing patterning. But it was difficult to study
adaptive introgression in humans until the first Neanderthal genome was
sequenced in 2010, providing scientists with hominin DNA to compare to our own.
Neanderthals and Denisovans would have been a good
source of helpful DNA for our ancestors. They had lived in Europe and Asia for
hundreds of thousands of years—enough time to adjust to the cold climate, weak
sun and local microbes. “What better way to quickly adapt than to pick up a
gene variant from a population that had probably already been there for 300,000
years?” Akey said.
Indeed, the Neanderthal and Denisovan genes with the
greatest signs of selection in the modern human genome “largely have to do with
how humans interact with the environment,” he said.
To find these adaptive segments, scientists search
the genomes of contemporary humans for regions of archaic DNA that are either
more common or longer than expected. Over time, useless pieces of Neanderthal
DNA—those that don’t help the carrier—are likely to be lost. And long sections
of archaic DNA are likely to be split into smaller segments unless there is
selective pressure to keep them intact.
In 2014, two groups, one led by Akey and the other
by David Reich, a geneticist at Harvard
Medical School, independently published genetic maps that
charted where in our genomes Neanderthal DNA is most likely to be found. To
Akey’s surprise, both maps found that the most common adaptive
Neanderthal-derived genes are those linked to skin and hair growth. One of the
most striking examples is a gene called BNC2, which is linked to
skin pigmentation and freckling in Europeans.
Nearly 70 percent of Europeans
carry the Neanderthal version.
Scientists surmise that BNC2 and
other skin genes helped modern humans adapt to northern climates, but it’s not
clear exactly how. Skin can have many functions, any one of which might have
been helpful. “Maybe skin pigmentation, or wound healing, or pathogen defense,
or how much water loss you have in an environment, making you more or less
susceptible to dehydration,” Akey said. “So many potential things could be
driving this—we don’t know what differences were most important.”
* * *
One of the deadliest foes that modern humans had to
fight as they ventured into new territories was also the smallest—novel
infectious diseases for which they had no immunity. “Pathogens are one of the
strongest selective forces out there,” said Janet Kelso, a bioinformatician at the
Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.
Earlier this year, Kelso and collaborators
identified a large stretch of Neanderthal DNA—143,000 DNA base-pairs long—that
may have played a key role in helping modern humans fight off disease. The
region spans three different genes that are part of the innate immune system, a
molecular surveillance system that forms the first line of defense against
pathogens. These genes produce proteins called toll-like receptors, which help immune cells
detect foreign invaders and trigger the immune system to attack.
Modern humans can have several different versions
of this stretch of DNA. But at least three of the variants appear to have come
from archaic humans—two from Neanderthals and one from Denisovans.
To figure
out what those variants do, Kelso’s team scoured public databases housing reams
of genomic and health data. They found that people carrying one of the
Neanderthal variants are less likely to be infected with H. pylori,
a microbe that causes ulcers, but more likely to suffer from common allergies
such as hay fever.
Kelso speculates that this variant might have
boosted early humans’ resistance to different kinds of bacteria. That would
have helped modern humans as they colonized new territories. Yet this added
resistance came at a price. “The trade-off for that was a more sensitive immune
system that was more sensitive to nonpathogenic allergens,” said Kelso.
But she
was careful to point out that this is just a theory. “At this point, we can
hypothesize a lot, but we don’t know exactly how this is working.”
Most of the Neanderthal and Denisovan genes found
in the modern genome are more mysterious. Scientists have only a vague idea of
what these genes do, let alone how the Neanderthal or Denisovan version might
have helped our ancestors. “It’s important to understand the biology of these
genes better, to understand what selective pressures were driving the changes
we see in present-day populations,” Akey said.
A number of studies like Kelso’s are now under way,
trying to link Neanderthal and Denisovan variants frequently found in contemporary
humans with specific traits, such as body-fat distribution, metabolism or other
factors.
One study of roughly 28,000 people of European descent, published in Science in February, matched
archaic gene variants with data from electronic health records. Overall,
Neanderthal variants are linked to higher risk of neurological and psychiatric
disorders and lower risk of digestive problems. (That study didn’t focus on
adaptive DNA, so it’s unclear how the segments of archaic DNA that show signs
of selection affect us today.)
At present, much of the data available for such
studies is weighted toward medical problems—most of these databases were
designed to find genes linked to diseases such as diabetes or schizophrenia.
But a few, such as the U.K. Biobank, are much broader, storing information on
participants’ vision, cognitive test scores, mental health assessments, lung
capacity and fitness.
Direct-to-consumer genetics companies also have large,
diverse data sets. For example, 23andMe analyzes users’ genetics for clues
about ancestry, health risk and other sometimes bizarre traits, such as whether
they have a sweet tooth or a unibrow.
Of course, not all the DNA we got from Neanderthals
and Denisovans was good. The majority was probably detrimental. Indeed, we tend
to have less Neanderthal DNA near genes, suggesting that it was weeded out by
natural selection over time. Researchers are very interested in these parts of
our genomes where archaic DNA is conspicuously absent.
“There are some really
big places in the genome with no Neanderthal or Denisovan ancestry as far as we
can see—some process is purging the archaic material from these regions,”
Sankararaman said. “Perhaps they are functionally important
for modern humans.”
SOURCE: https://www.quantamagazine.org/how-neanderthal-dna-helps-humanity-20160526/?utm_source=Quanta+Magazine&utm_campaign=510f4dd932-EMAIL_CAMPAIGN_2017_08_24&utm_medium=email&utm_term=0_f0cb61321c-510f4dd932-389390733
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