Modern humans inherited Neanderthal viral defenses

Neanderthals mysteriously disappeared about 40,000 years ago, but before disappearing, they crossed paths with another human species that was just beginning to spread around the world. As a result of these old discussions, many Europeans and modern Asians today host about 2% of Neanderthal DNA in their genome.

Curiously, fragments of Neanderthal DNA appear more often in modern human populations, prompting scientists to wonder whether their propagation was propelled by chance or whether these frequent genes confer a functional advantage.

Stanford scientists have now found convincing evidence of these. "Our research shows that a large number of frequent Neanderthal DNA extracts have been adapted for a very cool reason," said evolutionary biologist Dmitry Petrov, Professor Michelle and Kevin Douglas at the Faculty of Human Sciences. "The Neanderthal genes have probably afforded us some protection against the viruses our ancestors encountered when they left Africa."

At the first contact between the two species, Neanderthals had been living off Africa for hundreds of thousands of years, thus leaving their immune systems with enough time to develop defenses against infectious viruses in Europe and Europe. in Asia. In comparison, our newly immigrated ancestors would have been much more vulnerable. "It was much more logical for modern humans to borrow from Neanderthals the already adapted genetic defenses rather than wait for the development of their own adaptive mutations, which would have taken much longer," said David Enard, former Fellow. postdoctoral fellow at Petrov's laboratory. .

Petrov and Enard stated that their findings were consistent with a "poison" gene exchange model between two species. In this scenario, Neanderthals bequeathed to modern humans not only infectious viruses, but also genetic tools to fight against invaders.

"Modern humans and Neanderthals are so closely linked that it was not really a genetic barrier against the occurrence of these viruses," said Enard, who is now an assistant professor at the University of California. University of Arizona. "But this proximity also meant that Neanderthals could send us protections against these viruses."

In their new study, published online October 4 in the newspaper Cell, scientists have shown that the genetic defenses that Neanderthals have passed on to us are against RNA viruses, which encode their genes with RNA, a molecule chemically similar to DNA.

Persistent genes

Scientists have reached their conclusions after compiling a list of more than 4,500 genes in modern humans, known to interact one way or another with viruses. Enard then checked his list against a sequenced Neanderthal DNA database and identified 152 fragments of these genes from modern humans, also present in Neanderthals.

Scientists have shown that in modern humans, the 152 genes inherited from Neanderthals interact with HIV, influenza A and hepatitis C, all types of RNA viruses. Enard and Petrov concluded that these genes had helped our ancestors protect themselves from the old RNA viruses they had encountered while leaving Africa.

It is interesting to note that the Neanderthal genes they identified are present only in modern Europeans, suggesting that different viruses have influenced genetic exchanges between Neanderthals and the ancestors of today's Asians. That makes sense, said Enard, because it is thought that the miscegenation between Neanderthals and modern humans occurred several times and in many places in prehistory, and that different viruses were probably involved in each case.

In addition to offering a new perspective on crossbreeding between Neanderthals and humans, new discoveries also demonstrate that it is possible to sift the genome of a species and find evidence of old diseases. which once affected it, even when the viruses responsible for these diseases are long. faded away. This technique would work particularly well for RNA viruses, whose RNA-based genomes are more fragile than their DNA counterparts, says Enard.

"It's similar to paleontology," he added. "You can find clues about dinosaurs in different ways. Sometimes you will discover real bones, but sometimes you will only find footprints in the fossilized mud. Our method is also indirect: since we know which genes interact with which viruses, we can deduce the types of viruses responsible for epidemics of old diseases. "

Petrov is Associate Chair of the Department of Biology and Director of the Conservation Genomics Program at the Computer-Aided, Evolutionary and Human Genomics Center. He is also a member of the group Stanford Woods Institute for the Environment and a member of Stanford Bio-X and the Institute for Research on Children's Health. The research was funded by the National Institutes of Health.