A Single Neanderthal Gene Differentiates African from European Immune Systems

The African immune system has a downside—a higher risk of an autoimmune disorder.

 

You would think that since we are actually all one race, the human race, we would have the same susceptibility to diseases. But in fact, there is tremendous variance among the immune systems of different peoples living in varying parts of the world. The likelihood of developing certain infections, autoimmune diseases, or inflammatory conditions varies greatly, depending on where in the world your ancestors hailed. The immune systems of those of African and European descent diverge for instance, due to the different health challenges each population faced, historically.


Now, two new studies published in the journal Cell, help us to understand more about these differences. African immune systems are by and large stronger than their European counterparts, researchers found. Some of these variations can be traced back on the genetic level to proto-Europeans interbreeding with Neanderthals, which weakened their immune systems, over Africans who did not.

Homo sapiens left Africa somewhere between 100,000 and 60,000 years ago, and encountered a Europe already colonized by Neanderthals. Eventually, the two interbred, and the immune responses of Neanderthals helped homo sapiens adapt to their new environment and the pathogens there. Sometime after, around 40,000 years ago, Neanderthals vanished from the Earth. Today 20% of the world population carries Neanderthal genes within them.

Since Europe had a colder climate, a subtler inflammatory response was sufficient, researchers believe. However, in Africa, pathogens are more robust and so a faster immune response was required to ensure survival. Though they may respond better to pathogens, having an African immune system does have a downside, a higher risk of an autoimmune disorders.

Lluis Quintana-Murci of Institut Pasteur and CNRS in Paris, led one study. He said their findings show that such differences are responses that have been transcribed into DNA. Since the single gene they discovered was passed on by Neanderthals already living in Europe, it is considered something that conveyed an evolutionary advantage.

 

The earliest homo sapiens to settle Europe interbred with Neanderthals and benefited from their immune systems.

RNA sequencing was used by Quintana-Murci and his team, to categorize immune cells called primary monocytes, taken from 200 participants, half of European and the other African ancestry. Researchers looked at how the cells would respond when encountering a certain bacteria or virus. Differences in gene activity within immune cells varied widely between populations. What differentiated these two studies from others is not only studying immune response but the gene expression behind them.

Quintana-Murci and colleagues found that changes in a single gene, adopted from Neanderthals, became integral in the modern day European immune system and how it responds to pathogens. This discovery offers substantial evidence pertaining to gene selection and immune response. Certain regulatory variants too came from Neanderthals, which Europeans “borrowed” when the two interbred. This all plays out in how a Caucasian immune system responds to viral infections.

Luis Barreiro was the senior author of the other study. Barreiro hails from University of Montreal and the CHU Sainte-Justine, also in Canada. He and his team tested how African and European immune systems, particularly cells known as primary macrophages, responded to live, pathogenic bacteria. The macrophages of 175 Americans, 80 African Americans and 95 Caucasians, were used. These cells were grown in dishes and then infected with either listeria or salmonella bacteria.  

Le Moustier Neanderthals by: Charles Robert Knight, Public Domain, Wikipedia Commons

After infecting them, Barreiro and colleagues returned 24 hours later to see how each cell responded. Those of an African descent showed an inflammatory response three times faster than that of European Americans. But this also had a disadvantage. A more active immune system comes with a higher risk of autoimmune disorders, such as Crohn’s disease. This is why African American women are three times more likely to develop Lupus than white ones, for example. After that, researchers examined the genes behind these responses and found that 12,000 of them, approximately 30% of the total, were expressed differently between these two races.

More research will need to be conducted to see how immune systems of different races and ethnicities act in different ways. This research may someday lead to more personalized treatment options, properly tailored to the patient’s biology. Previously, the molecular and genetic basis for immune system differences has been a mystery, Bareiro said. This research illustrates how the history of natural selection continues to influence us to this day.

Everything about disease resistance does not reside with the genes, however. According to Barreiro, "Genetics explains only about 30% of the observed differences in immune responses.” Diet, exercise, environmental influences, smoking, and other factors, tell a lot more of the story. Barreiro added that future studies should quantify what exact influence genetics have, and to what extent lifestyle choices and other factors contribute to overall health. Another issue is the lack of diversity in genomic-wide studies. 80% of genetic and biological samples have come from Caucasians, a recent comment in the journal Nature pointed out. This study illustrates just how critical knowing such differences is.

To learn more about the exploits of our ancient ancestors and how it affects us today, click here: 

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New fossils suggest human ancestors evolved in Europe, not Africa

Experts argue the jaws of an ancient European ape reveal a key human ancestor.

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Homo sapiens have been on earth for 200,000 years — give or take a few ten-thousand-year stretches. Much of that time is shrouded in the fog of prehistory. What we do know has been pieced together by deciphering the fossil record through the principles of evolutionary theory. Yet new discoveries contain the potential to refashion that knowledge and lead scientists to new, previously unconsidered conclusions.

A set of 8-million-year-old teeth may have done just that. Researchers recently inspected the upper and lower jaw of an ancient European ape. Their conclusions suggest that humanity's forebearers may have arisen in Europe before migrating to Africa, potentially upending a scientific consensus that has stood since Darwin's day.

Rethinking humanity's origin story

The frontispiece of Thomas Huxley's Evidence as to Man's Place in Nature (1863) sketched by natural history artist Benjamin Waterhouse Hawkins. (Photo: Wikimedia Commons)

As reported in New Scientist, the 8- to 9-million-year-old hominin jaw bones were found at Nikiti, northern Greece, in the '90s. Scientists originally pegged the chompers as belonging to a member of Ouranopithecus, an genus of extinct Eurasian ape.

David Begun, an anthropologist at the University of Toronto, and his team recently reexamined the jaw bones. They argue that the original identification was incorrect. Based on the fossil's hominin-like canines and premolar roots, they identify that the ape belongs to a previously unknown proto-hominin.

The researchers hypothesize that these proto-hominins were the evolutionary ancestors of another European great ape Graecopithecus, which the same team tentatively identified as an early hominin in 2017. Graecopithecus lived in south-east Europe 7.2 million years ago. If the premise is correct, these hominins would have migrated to Africa 7 million years ago, after undergoing much of their evolutionary development in Europe.

Begun points out that south-east Europe was once occupied by the ancestors of animals like the giraffe and rhino, too. "It's widely agreed that this was the found fauna of most of what we see in Africa today," he told New Scientists. "If the antelopes and giraffes could get into Africa 7 million years ago, why not the apes?"

He recently outlined this idea at a conference of the American Association of Physical Anthropologists.

It's worth noting that Begun has made similar hypotheses before. Writing for the Journal of Human Evolution in 2002, Begun and Elmar Heizmann of the Natural history Museum of Stuttgart discussed a great ape fossil found in Germany that they argued could be the ancestor (broadly speaking) of all living great apes and humans.

"Found in Germany 20 years ago, this specimen is about 16.5 million years old, some 1.5 million years older than similar species from East Africa," Begun said in a statement then. "It suggests that the great ape and human lineage first appeared in Eurasia and not Africa."

Migrating out of Africa

In the Descent of Man, Charles Darwin proposed that hominins descended out of Africa. Considering the relatively few fossils available at the time, it is a testament to Darwin's astuteness that his hypothesis remains the leading theory.

Since Darwin's time, we have unearthed many more fossils and discovered new evidence in genetics. As such, our African-origin story has undergone many updates and revisions since 1871. Today, it has splintered into two theories: the "out of Africa" theory and the "multi-regional" theory.

The out of Africa theory suggests that the cradle of all humanity was Africa. Homo sapiens evolved exclusively and recently on that continent. At some point in prehistory, our ancestors migrated from Africa to Eurasia and replaced other subspecies of the genus Homo, such as Neanderthals. This is the dominant theory among scientists, and current evidence seems to support it best — though, say that in some circles and be prepared for a late-night debate that goes well past last call.

The multi-regional theory suggests that humans evolved in parallel across various regions. According to this model, the hominins Homo erectus left Africa to settle across Eurasia and (maybe) Australia. These disparate populations eventually evolved into modern humans thanks to a helping dollop of gene flow.

Of course, there are the broad strokes of very nuanced models, and we're leaving a lot of discussion out. There is, for example, a debate as to whether African Homo erectus fossils should be considered alongside Asian ones or should be labeled as a different subspecies, Homo ergaster.

Proponents of the out-of-Africa model aren't sure whether non-African humans descended from a single migration out of Africa or at least two major waves of migration followed by a lot of interbreeding.

Did we head east or south of Eden?

Not all anthropologists agree with Begun and his team's conclusions. As noted by New Scientist, it is possible that the Nikiti ape is not related to hominins at all. It may have evolved similar features independently, developing teeth to eat similar foods or chew in a similar manner as early hominins.

Ultimately, Nikiti ape alone doesn't offer enough evidence to upend the out of Africa model, which is supported by a more robust fossil record and DNA evidence. But additional evidence may be uncovered to lend further credence to Begun's hypothesis or lead us to yet unconsidered ideas about humanity's evolution.