[DNA fragments from thousands of years ago are providing insights
into multiple sclerosis, diabetes, schizophrenia and other illnesses.]
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SUNDAY SCIENCE: ANCIENT SKELETONS GIVE CLUES TO MODERN MEDICAL
MYSTERIES  
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Carl Zimmer
January 10, 2024
New York Times
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_ DNA fragments from thousands of years ago are providing insights
into multiple sclerosis, diabetes, schizophrenia and other illnesses.
_

A 4,000-year-old skeleton of a Yamnaya person found in Bulgaria.,
Michal Podsiadlo

 

Multiple sclerosis, an autoimmune disease that affects 2.9 million
people
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presents a biological puzzle.

Many researchers suspect that the disease is triggered by a
virus, known as Epstein-Barr
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which causes the immune system to attack the nerves and can leave
patients struggling to walk or talk. But the virus can’t be the
whole story, since nearly everyone is infected with it at some point
in life.

A new study found
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solution to this paradox in the skeletal remains of a lost tribe of
nomads who herded cattle across the steppes of western Asia 5,000
years ago. It turns out that the nomads carried genetic mutations that
most likely protected them from pathogens carried by their animals,
but that also made their immune systems more sensitive. These genes,
the study suggests, made the nomads’ descendants prone to a runaway
immune response.

The finding is part of a larger, unprecedented effort to understand
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evolutionary past has shaped the health of living people. Researchers
are analyzing thousands of genomes of people who lived between
Portugal and Siberia and between Norway and Iran roughly 3,000 to
11,000 years ago. They hope to trace the genetic roots of not only
multiple sclerosis, but also diabetes, schizophrenia and many other
modern illnesses.

“We are taking ancient human genomics to a whole new level,” said
Eske Willerslev, a geneticist at the University of Copenhagen who led
the effort.

The researchers published the multiple sclerosis study as well as
three other papers on the genetics and health of ancient peoples on
Wednesday in the journal Nature.

For more than a decade, Dr. Willerslev and other researchers
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been pulling DNA from ancient human bones
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By comparing the surviving genetic material with that of living
people, the scientists have been able to track some of the most
significant migrations of people across the world.

For example, they have chronicled the movement of farmers from what is
now Turkey across Europe starting about 8,000 years ago. These early
farmers encountered European hunter-gatherers who had lived
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the continent for more than 30,000 years. In some places,
hunter-gatherer DNA vanished from skeletons after the arrival of the
farmers, suggesting violent conflicts. In other places, the two
populations mingled enough to produce later generations with a mixed
ancestry.

Thousands of years passed before the next big migrational shift. About
5,000 years ago, European DNA began to show the genetic signatures of
a group of pastoralists who lived on the steppes that stretch from
Ukraine to Kazakhstan, called the Yamnaya.

The Yamnaya traveled on horses and in wagons across hundreds of miles
of grassland, herding cows, goats and sheep along the way. Even
without farms or cities, they prospered for centuries, burying their
dead with gold and jewelry.

In the Bronze Age, the Yamnaya expanded their territory, sweeping
through much of Asia as well as Europe. Dr. Willerslev and his
colleagues have found that once in Europe, the group often wiped out
the farmers it encountered, although they also had peaceful relations
in some places.

Today, people in northern Europe can trace most of their ancestry to
the Yamnaya. Farther south, Yamnaya ancestry is less common. People
there instead have more ancestry from Near East farmers and Europe’s
earlier hunter-gatherers.

Dr. Willerslev and his colleagues wondered what kind of genetic
variations each ancient group carried by each ancient group and how
they affected their health. To find out, the researchers studied some
of their living descendants.

They took advantage of UK Biobank, a huge database of DNA and medical
information. Most of the 433,395 volunteers whom the scientists
studied were born in Britain, but 24,511 were born in other countries.

The researchers were able to tie thousands of genetic variants in the
database to increased risks for a wide range of diseases. They then
compared the volunteers’ DNA with the genetic fragments from ancient
skeletons.

One analysis found that hunter-gatherers from Western Europe, for
example, carried many of the variants that raise the risk for high
cholesterol, high blood pressure and diabetes. Another showed that
ancient Near East farmers carried a high burden of variants linked to
anxiety and other mood disorders.

These findings don’t necessarily mean that these ancient people
suffered from these conditions. Genetic variants lay the trap, but
it’s often the environment that springs it.

Diabetes, for example, has become increasingly common in the modern
world, in part because of the cheap, sugar-loaded food that makes up
an increasing part of our diet. In earlier centuries, high-risk genes
for diabetes may not have had the opportunity to give rise to the
disease.

In some cases, Dr. Willerslev and his colleagues found, these genetic
variants provided ancient peoples with a survival advantage.

The variants that raise the risk of multiple sclerosis, for example,
became steadily more common among the Yamnaya. The nomads who carried
them appear to have had more offspring than those who didn’t.

“These variants that are causing the high risk of multiple sclerosis
today must in the past have had a benefit,” Dr. Willerslev said.

The new studies give some strong hints about what that benefit is.
Some of the skeletons contained DNA not just from humans, but also
from disease-causing viruses and bacteria. Many of these pathogens did
not appear among hunter-gatherers or even among the earliest farmers
in Europe. But the Yamnaya remains contained the genetic signatures of
a number of pathogens, including the one that caused plague
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“These variants seem to give some kind of protection from infectious
diseases,” Dr. Willerslev said.

A number of studies on multiple sclerosis suggest that the variants
that raise the risk of the disease also make the immune system’s
attack against viruses and bacteria more aggressive.

 

Dr. Willerslev and his colleagues argued that the Yamnaya were more
vulnerable to animal diseases than previous humans were. The Yamnaya
depended on animals for meat and milk and were in constant contact
with their herds as they moved across the steppes.

Those conditions provided a new opportunity for diseases to jump to
humans. In response, the Yamnaya evolved immune-related genes that
helped them fend off the new enemies.

“They’ve made a really, really compelling case,” Yassine
Souilmi, a genomicist at the University of Adelaide in Australia, said
of Dr. Willerslev and his colleagues. “I’ll be shocked if further
experimental testing doesn’t match their conclusions.”

Dr. Lars Fugger, a multiple sclerosis expert at the University of
Oxford who collaborated with Dr. Willerslev on the new studies, said
that the disease may not have become common until recent decades. In
today’s environment, with less infectious disease than past
centuries, he said, a strong immune system becomes more likely to
misfire, attacking its own body.

“Many of us are living in an environment that is squeaky clean,”
Dr. Fugger said. “The balance is no longer there.”

 

Understanding the evolutionary roots of multiple sclerosis could guide
researchers to better treatments for the disease. Currently, the only
effective treatments for the condition are drugs that suppress the
immune system. To Dr. Fugger, those drugs seem like blunt instruments
against a delicately balanced part of our biology.

“Rather than just knocking it out, we should just try to find out in
greater detail how it’s unbalanced, and then try to recalibrate
it,” he said.

The researchers are starting similar analyses of other diseases, such
as schizophrenia and psoriasis. “This is just the beginning,” Dr.
Fugger said.

For now, they are continuing to rely on the UK Biobank, which means
their results will be largely limited to genes that have influenced
the health of northern Europeans. “It would be phenomenal to have
similar studies in other parts of the world,” said Lluis
Quintana-Murci, an evolutionary geneticist at Institut Pasteur who was
not involved in the research.

But there are few opportunities to carry out such studies. Many
countries lack detailed electronic health records, for one thing. And
unethical behavior of Western scientists has left many Indigenous
populations uninterested in donating DNA
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such efforts.

Dr. Souilmi, who is helping to build a database
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Indigenous Australians, said that the different evolutionary path of
each population could reveal important insights about human biology in
general. “By studying other parts of the world, we’re actually
broadening our understanding of all human conditions today,” he
said.

_CARL ZIMMER [[link removed]] covers news
about science for The Times and writes the Origins column
[[link removed]]. I report on life — from
microbes at the bottom of the sea to high-flying migratory birds to
aliens that may dwell on other planets. For my column, I focus on how
life today got its start, including our own species. Along with
covering basic science, I write stories about how biological
discoveries evolve into medical applications, such as editing genes
and tending to our microbiome. _

_I wrote my first story for The Times in 2004. In 2013 I became a
columnist. I began my career in journalism at Discover Magazine, where
I rose to senior editor. I went on to write articles for magazines
including The Atlantic, Scientific American, Wired and Time._

_I also write books about science. So far, I’ve published 14,
including “She Has Her Mother’s Laugh,” “Life’s Edge,” and
“Parasite Rex.” I am professor adjunct at Yale’s Department of
Molecular Biophysics and Biochemistry, where I teach seminars on
writing and biology lecture courses. I have also co-authored a
textbook on evolutionary biology, now in its fourth edition._

_My books and articles have earned a number of awards including the
National Academics Communication Award and the Stephen Jay Gould
Prize, given out by the Society for the Study of Evolution. I have won
fellowships from the Johns Simon Guggenheim Foundation and the Alfred
P. Sloan Foundation. During the Covid-19 pandemic, I contributed to
the coverage that won The Times the Pulitzer Prize for Public Service
in 2021. I am, to my knowledge, the only writer after whom both a
species of tapeworm and an asteroid have been named._

_I live with my wife in Connecticut, alongside salt marshes rife with
snapping turtles._

_Subscribe to the NEW YORK TIMES.
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__

The Link Between Climate Change and a Spate of Rare Disease Outbreaks
in 2023
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Zoya Teirstein
The temperature-sensitive pathogens that caught U.S. communities off
guard are a grim preview of the future.
GRIST
December 22, 2023

* Science
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* biology
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* Medicine
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* DNA
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* migration
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* disease
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* Evolution
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