[Our Homo sapiens ancestors shared the world with Neanderthals,
Denisovans and other types of humans whose DNA lives on in our genes.
Unearthing those extinct genomes has profound practical and
philosophical implications. ]
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UNEARTHING SECRETS OF OUR SHARED HUMAN DNA  
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Joshua Akey
October 7, 2022
The Conversation
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_ Our Homo sapiens ancestors shared the world with Neanderthals,
Denisovans and other types of humans whose DNA lives on in our genes.
Unearthing those extinct genomes has profound practical and
philosophical implications. _

Skulls of Homo sapiens and Homo neanderthalensis,

 

When the first modern humans arose
[[link removed]] in East
Africa sometime between 200,000 and 300,000 years ago, the world was
very different compared to today. Perhaps the biggest difference was
that we – meaning people of our species, _Homo sapiens_ – were
only one of several types of humans (or hominins
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that simultaneously existed on Earth.

From the well-known Neanderthals
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and more enigmatic Denisovans
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in Eurasia, to the diminutive “hobbit” _Homo floresiensis_
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on the island of Flores in Indonesia, to _Homo naledi_ that lived in
South Africa
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multiple hominins abounded.

Then, between 30,000 and 40,000 years ago, all but one type of these
hominins disappeared
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and for the first time we were alone.

Until recently, one of the mysteries about human history was whether
our ancestors interacted and mated with these other types of humans
before they went extinct. This fascinating question was the subject of
great and often contentious debates among scientists for decades
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because the data needed to answer this question simply didn’t exist.
In fact, it seemed to many that the data would never exist.

Svante Pääbo
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however, paid little attention to what people thought was or was not
possible. His persistence in developing tools to extract, sequence and
interpret ancient DNA enabled sequencing the genomes of Neanderthals
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For developing this new field of paleogenomics
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Pääbo was awarded the 2022 Nobel Prize in Physiology or Medicine.
This honor is not only well-deserved recognition for Pääbo’s
triumphs, but also for evolutionary genomics and the insights it can
contribute toward a more comprehensive understanding of human health
and disease.

[Diagram of human lineages diverging and interbreeding over time]
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A simplified model of human evolution showing how humans are related
to Neanderthals and Denisovans. Arrows between different branches show
mating that occurred. Events that happened further back in time are
closer to the top of the image. Joshua Akey, CC BY-ND
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Mixing and mating, revealed by DNA

Genetic studies of living people over the past several decades
revealed the general contours of human history. Our species arose in
Africa, dispersing out from that continent around 60,000 years ago,
ultimately spreading to nearly all habitable places on Earth. Other
types of humans existed as modern humans migrated throughout the
world, but the genetic data showed little evidence that modern humans
mated with other hominins.

Over the past decade, however, the study of ancient DNA, recovered
from fossils up to around 400,000 years old
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has revealed startling new twists and turns in the story of human
history.

For example, the Neanderthal genome provided the data necessary to
definitively show that humans and Neanderthals mated. Non-African
people alive today inherited about 2% of their genomes
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Neanderthal ancestors, thanks to this kind of interbreeding.

In one of the biggest surprises, when Pääbo and his colleagues
sequenced ancient DNA obtained from a small finger bone fragment that
was assumed to be Neanderthal, it turned out to be an entirely unknown
type of human, now called Denisovans
[[link removed]]. Humans and Denisovans also
mated
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with the highest levels of Denisovan ancestry present today –
between 4% and 6% – in individuals of Oceanic ancestry.

Strikingly, ancient DNA from a 90,000-year-old female revealed that
she had a Neanderthal mother and a Denisovan father
[[link removed]]. Although there are still
many unanswered questions, the picture emerging from analyses of
ancient and modern DNA is that not only did multiple hominins overlap
in time and space, but that matings were relatively common.

[artist's recreation of Neanderthal man wearing a modern business
suit]
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Does a Neanderthal in modern clothing makes it easier to imagine
mingling with his species? picture alliance via Getty Images
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Archaic genes you carry today

Estimating the proportion of ancestry that modern individuals have
from Neanderthals or Denisovans is certainly interesting. But ancestry
proportions provide limited information about the consequences of
these ancient matings.

For instance, does DNA inherited from Neanderthals and Denisovans
influence biological functions that occur within our cells? Does this
DNA influence traits like eye color or susceptibility to disease? Were
DNA sequences from our evolutionary cousins ever beneficial, helping
humans adapt to new environments?

To answer these questions, we need to identify the bits of Neanderthal
and Denisovan DNA scattered throughout the genomes of modern
individuals.

In 2014, my group [[link removed]] and David Reich’s
group [[link removed]] independently published the
first maps of [[link removed]]
Neanderthal sequences [[link removed]]
that survive in the DNA of modern humans. Today, roughly 40% of the
Neanderthal genome has been recovered not by sequencing ancient DNA
recovered from a fossil, but indirectly by piecing together the
Neanderthal sequences [[link removed]] that
persist in the genomes of contemporary individuals.

Similarly, in 2016 my group [[link removed]]
and David Reich’s group [[link removed]]
published the first comprehensive catalogs of DNA sequences in modern
individuals inherited from Denisovan ancestors. Surprisingly, when we
analyzed the Denisovan sequences that persist in people today, we
discovered they came from two distinct Denisovan populations, and
therefore at least two separate waves of matings occurred between
Denisovans and modern humans
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The analysis of Neanderthal and Denisovan DNA in modern humans reveals
that some of their sequence was harmful and rapidly got purged from
human genomes. In fact, the initial fraction of Neanderthal ancestry
in humans who lived approximately 45,000 years ago was around 10%.
That amount rapidly declined over a small number of generations to the
2% observed in contemporary individuals
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The removal of deleterious archaic sequences also created large
regions of the human genome that are significantly depleted of both
Neanderthal and Denisovan ancestry. These deserts of archaic hominin
sequences are interesting because they may help identify genetic
changes that contribute to uniquely modern human traits
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for language, symbolic thought and culture, although there is debate
about just how unique these traits are to modern humans
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In contrast, there are also sequences inherited from Neanderthals and
Denisovans that were advantageous, and helped modern humans adapt to
new environments as they dispersed out of Africa. Neanderthal versions
of several immune-related genes have risen to high frequency in
several non-African populations, which likely helped humans fend off
exposure to new pathogens
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Similarly, a version of the _EPAS1_ gene, which contributes to
high-altitude adaptation
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in Tibetan populations, was inherited from Denisovans.

It is also becoming clear that DNA sequences inherited from
Neanderthal and Denisovan ancestors contribute to the burden of
disease in present day individuals. Neanderthal sequences have been
shown to influence both susceptibility to
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severe COVID-19 [[link removed]]. Archaic
hominin sequences have also been shown to influence
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depression, Type 2 diabetes and celiac disease among others. Ongoing
studies will undoubtedly reveal more about how Neanderthal and
Denisovan ancestry contributes to human disease.

[photo of man holding a human skull and looking at the face]
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Svante Pääbo’s work built the foundation of the new field of
paleogenomics. Jens Schluete via Getty Images News
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I was a graduate student when the Human Genome Project
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was nearing completion a little over two decades ago. I was drawn to
genetics because I found it fascinating that, by analyzing the DNA of
present-day individuals, you could learn aspects about a
population’s history that occurred tens of thousands of years ago.

Today, I am just as fascinated by the stories contained in our DNA,
and the work of Svante Pääbo and his colleagues has enabled these
stories to be told in a way that simply was not possible before.[The
Conversation]

Joshua Akey
[[link removed]], Professor
at the Lewis-Sigler Institute for Integrative Genomics, _Princeton
University
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This article is republished from The Conversation
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the original article
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* Science
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* paleontology
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* Evolution
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* human evolution
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* DNA
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