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Bloody Biology

Neanderthal blood study hints at one possible reason they went extinct

A landmark analysis reveals what we can learn from blood.

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In 1901, biologist Karl Landsteiner made a landmark discovery: Human blood contains different types of groups. This finding led to a Nobel Prize and the eventual discovery of the four specific blood types: A, B, O, and AB.

Today, more than a century later, Landsteiner‘s discovery is why millions of people receive life-saving blood transfusions. But more peculiarly, it’s allowed for an unprecedented look into the lives, and eventual demise, of ancient humans.

Scientists recently analyzed the blood types of the Denisovans and Neanderthals, two now extinct members of our genus. In a study published Wednesday in the journal PLOS One, they claim the analysis points to new clues about the origin of these humans, their health, and how their genetics influence people alive today.

These include insight into early interbreeding with Homo sapiens, a previously unknown genetic link to modern humans, and evidence of a genetic disease that may have hampered reproductive success.

How they made the discovery — To know a person’s blood type, you don’t actually need access to their blood.

The study team analyzed ancient genetic data collected by the Max Planck Department of Evolutionary Genetics to determine blood type — blood type is determined by changes in the amino acids of certain alleles. Like hair or eye color, blood type is inherited.

“Blood group systems were not known in Neanderthals and Denisovans.”

The team was also looking to identify the presence of genetic variation across Neanderthals and Denisovans, a concept known as polymorphism.

Co-author Silvana Condemi is the research director of the National Center for Scientific Research in France. The effort to identify polymorphism, she tells Inverse, came with the aim to “bring a complementary view on the evolutionary history of the human lineage.”

What’s new — For the first time, scientists discovered that Neanderthals and Denisovans possess the ABO blood groups, which contain antigens that are important for modern blood transfusions.

This is the first time ABO blood groups have been confirmed in humans beyond modern-day Homo sapiens. It implies that the ancestors of Neanderthals, Denisovans, and Homo sapiens likely possessed these blood types too, Condemi says.

A Neanderthal skull on display in Paris, France. STEPHANE DE SAKUTIN/AFP via Getty Images

The team also analyzed the genes that secrete the ABO blood groups, finding a certain form of a gene called a “se” allele. This allele was previously only seen in modern-day humans. (Alleles are a set of genes that appear only in one location on a chromosome.)

Beyond the discovery of the ABO blood groups, Condemi and colleagues made five other critical discoveries:

  1. Scientists discovered a previously unknown allele called Rhd Duc2. This is found only in Neanderthals and in the blood types of some Aboriginal Australians and indigenous Papuans.
  2. The results suggest early interbreeding likely occurred between Neanderthals and modern humans after they emerged from Africa, likely somewhere in the present-day Middle East.
  3. The researchers found the molecular basis for the blood groups in Neanderthals and Denisovans, which was similar to the DNA found in modern people in Africa. This supports the idea that Neanderthals and Denisovans originated in Africa.
  4. In Denisovan and Neanderthal genetic data, the researchers found a gene associated with strong resistance to Norovirus, which causes an upset stomach. This gene expression hadn’t previously been found in non-human primates.

But perhaps most fascinating, is the finding of an allele associated with increased vulnerability to diseases that affect fetuses and newborns. A specific example is hemolytic disease, a blood disorder found in newborns. It’s possible this played a role in the eventual extinction of Neanderthals as it “contributes to a decrease in reproductive success,” Condemi explains.

Why this matters — Condemi argues that the study’s findings will “contribute to a better understanding of the history and evolution of modern man.”

“This shows the importance of the study of blood systems to understand the evolutionary history of humans, the diffusion in Eurasia of our species, as well as its encounters with other humans,” she says.

The dominance of modern man — Homo sapiens — coincided with the extinction of the Neanderthals roughly 40,000 years ago. To understand how modern man dominated planet Earth, we need to understand why Neanderthals disappeared.

While the study wasn’t designed with the intention of probing Neanderthal extinction, the research ultimately became “a new way to address this question,” Condemi says.

What’s next — While scientists have previously conducted genetic research on the remains of Denisovans and Neanderthals, few researchers have thought to analyze blood type.

“Blood group systems were not known in Neanderthals and Denisovans,” Condemi says.

Blood analysis is a unique tool, albeit one that needs a larger dataset of ancient genes to reach its full potential, Condemi says.

Until then, the research reveals pieces of the puzzle — deepening our understanding of how ancient humans lived and died, ultimately paving the way for our domination of Earth.

Abstract: Blood group systems were the first phenotypic markers used in anthropology to decipher the origin of populations, their migratory movements, and their admixture. The recent emergence of new technologies based on the decoding of nucleic acids from an individual’s entire genome has relegated them to their primary application, blood transfusion. Thus, despite the finer mapping of the modern human genome in relation to Neanderthal and Denisova populations, little is known about red cell blood groups in these archaic populations. Here we analyze the available high-quality sequences of three Neanderthals and one Denisovan individuals for 7 blood group systems that are used today in transfusion (ABO including H/ Se, Rh (Rhesus), Kell, Duffy, Kidd, MNS, Diego). We show that Neanderthal and Denisova were polymorphic for ABO and shared blood group alleles recurrent in modern Sub-Saharan populations. Furthermore, we found ABO-related alleles currently preventing from viral gut infection and Neanderthal RHD and RHCE alleles nowadays associated with a high risk of hemolytic disease of the fetus and newborn. Such a common blood group pattern across time and space is coherent with a Neanderthal population of low genetic diversity exposed to low reproductive success and with their inevitable demise. Lastly, we connect a Neanderthal RHD allele to two present-day Aboriginal Australian and Papuan, suggesting that a segment of archaic genome was introgressed in this gene in non-Eurasian populations. While contributing to both the origin and late evolutionary history of Neanderthal and Denisova, our results further illustrate that blood group systems are a relevant piece of the puzzle helping to decipher it.
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