When modern humans journeyed out of Africa, a rapid evolution in their red blood cells may have helped them survive — but it may have also led to the eventual disappearance of Neanderthals, a new study finds.
By sequencing the genomes of dozens of people who lived between 120,000 and 20,000 years ago, researchers found that Neanderthals had a rare blood group that could have been fatal to their newborns. Their study was published Thursday (Jan. 23) in the journal Scientific Reports.
Humans' blood groups are characterized by proteins and sugars — called antigens — found on the surface of red blood cells. Many people are familiar with the ABO blood typing system, which lumps blood into the groups A, B, AB and O. The antigens on a person's red blood cells are recognized as safe by the immune system, but someone with type B blood will have antibodies that attack type A antigens, for example.
Another important antigen is the Rh factor, which gives the "positive" and "negative" signs to blood types. So, nowadays, knowing which of the eight possible combinations of blood group and Rh factor a person has is key to a successful blood transfusion.
But red blood cells are even more complicated than this — there are hundreds of other, lesser-known antigens known to hang out on the surface of these cells in modern humans, as well as differences in the inside of the cells. Since these variations in red blood cells are passed down over the generations, a team of researchers at Aix-Marseille University in France decided to look into ancient genomes to better understand the evolutionary history of Neanderthals, Denisovans and humans.
Related: The mystery of the disappearing Neanderthal Y chromosome
"Neanderthals have an Rh blood group that is very rare in modern humans," study lead author Stéphane Mazières, a population geneticist at Aix-Marseille University, told Live Science in an email. This Rh variant — a type of RhD, another red blood cell antigen — is not compatible with the variants the team found in the Denisovans or the early Homo sapiens in their study.
"For any case of inbreeding of a Neanderthal female with a Homo sapiens or Denisova male," Mazières said, "there is a high risk of hemolytic disease of the newborn." The condition can lead to jaundice, severe anemia, brain damage and death.
"This could have contributed to the demise of the Neanderthal population," Mazières said.
Experts aren't sure why most modern humans have the Rh protein on the surface of their cells, nor why some people lack the protein, but an issue can arise if an Rh-negative person is pregnant with an Rh-positive fetus. In this scenario, called Rh incompatibility, the pregnant person's immune system may create antibodies and attack the fetus's red blood cells, leading to hemolytic disease of the newborn.
Treatment today for Rh incompatibility involves the prenatal administration of an immunoglobulin, a lab-made antibody, which prevents the pregnant person from making antibodies against the fetus's blood. But 100,000 years ago, this type of red blood cell incompatibility would have been impossible to treat.
Mazières and colleagues found that the Rh gene variants found in many people today come from early Homo sapiens ancestors, who appear to have evolved them soon after leaving Africa, possibly while living on the Persian Plateau. Neanderthals, on the other hand, had Rh variants compatible with one another but that remained largely unchanged throughout the last 80,000 years of their existence.
While Neanderthals' general isolation could explain why their red blood cells did not evolve much over the years, there are still questions about why early humans' red blood cells diversified so much and so quickly — over a span of at least 15,000 years.
"My first thought was because of a demographic expansion," Mazières said. "Then, probably that the novel environments of Eurasia may have helped to maintain them throughout the generations."
This research into red blood cell variations fits in well with archaeological and genetic studies, Mazières suggested, showing that new genetic lineages and new stone tool industries arose in the Persian Plateau between 70,000 and 45,000 years ago. The lack of diversity in the red blood cells of Neanderthals and Denisovans over the same time span could indicate inbreeding and declining population numbers, eventually leading to the extinction of these groups.
