From the fossilized skulls we know that his brain was bigger – a little bigger than ours, in fact – but it tells us little about his neurology and development.
Scientists at the University of California, San Diego have come up with a provocative and exciting way to answer this question. They created genetically modified blood tissue blobs to carry genes that belong to Neanderthals and other archaeological hominins, but not to Homo sapiens.
While the research is at a very early stage, researchers have found that neanderthalized brain organoids have undergone significant changes in how they are arranged and wired in the brain.
“The question here is what makes us human,” said Alison Muotri, professor and director of the stem cell program at the University of California San Diego School of Medicine Medicine Institute for Genomic Medicine.
“Why are our brains different from other species, including our own extinct relatives?”
Neuroarthology
Muotri, who has so far spent eight years on the project, calls his work “neuroarchiology.”
“When you get a piece of bone or (charcoal) and you try to reconcile how that society lives, what they’re doing, how they’re connected to each other – you try to understand the mind. We’re on the genetic side. But we’re doing the same level. ”
Muotri said the neanderthalized brain organoids were “pop popcorn shapes” compared to the more rounded, uniform shapes of modern humans. His team also observed that the neurons in organoids mature faster than modern humans.
“Neurons in the ancient version organoids, we see more activity in the very early stages than modern humans. We certainly did not expect it.”
He said he saw similar activity in his previous work on chimpanzee organoids.
“A baby chimpanzee can push a human newborn too far back. We should follow it until our babies become independent. We don’t see that in other species. I think that’s something we’re seeing here.”
However, Muotri insisted that this is speculative. Organoids are a long way from the real brain. For one, it lacks connections with other organs.
“We don’t know how the human brain, with these ancient versions, would behave,” he said. “All of these differences we see at an early stage can be overcome, because there are ways to compensate the brain.”
“But we know that a very early, subtle change in brain development can result in an adult brain. Take, for example, the genes involved in autism.”
Gene acquisition with archaeological material
We now know that many of us have Neanderthals, including DNA. There are traces of past encounters between early modern humans and Neanderthals, who inhabited parts of Europe and Asia about 1,000,000 years ago.
The UCSD team first compared the genomes of Neanderthals, Denisovans and modern human populations to find that genetic variants are not shared with our closest cousins.
“We asked what is unique about us? We just eliminated 61 protein-coding genes that differ between modern and archaeological humans,” Muotri said.
The team chose to focus on one gene called NOVA1 because it is considered the “master regulator” of other genes affecting early neurodevelopment in modern humans. He said the changes in the gene were linked to mental disorders such as schizophrenia and autism.
Since then, scientists have used the CRISPR gene acquisition technique, which won the Nobel Prize in Chemistry in 2020, to exchange modern NOVA1 genes for archaeological versions in human stem cells and to convert stem cells into organoids.
“It’s an extremely difficult set of experiments,” said Grace Camp, an assistant professor at the University of Basel in Switzerland, who was not involved in the research.
“Organoids are difficult to control. If there were all their controls, one would believe that this one amino acid change has a drastic effect on brain development. That’s abnormal.”
‘There is no magic that makes us human’
Such daring research naturally comes with warnings.
Gene acquisition is not a complete process, and inserting archaeological genes into human cells does not reproduce the Neanderthal genome as it really is, said Tony K. Rae, an associate professor of epidemiology and biostatics at the university’s Baker Computational Health Sciences. California, San Francisco.
“It’s challenging to say that the Neanderthal variant organoid results essentially reflect how the Neanderthal brain evolved,” he said via email. Kapra was not involved in the study.
“This mutation is being evaluated in the context of the human genome, so the archaeological variant is on a genetic background that does not reflect what the Neanderthal genome was like.”
Still, Capra was excited by the research, published Thursday in the journal Science. However, he warned that “we should not expect any magical variant out there from which we became human.
“Most of the traits that make us modern humans are much more genetically complex than Neanderthals (or chimpanzees),” said Karapara. “Thousands of parts of our genome contribute to neurology and development.”
He added, “Organoids are attractive because they enable us to test variants in more complex settings than single cells, but eventually we will need to completely ‘neutralize’ the organisms.”
Capra said recent archaeological research has suggested that Neanderthals had many cognitive abilities similar to those of early modern humans, but, like fossils and stone artifacts, that improbable neuroarthology could make certain decisions, Capra said.
“We will not be able to recreate the environmental and social context in which these individuals lived or where these events took place. The environment is so necessary to shape how the genome expresses itself that we always have to guess,” he said.
That said, I think we will learn a lot from bones and the genome in the coming years. “
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