It has been 200 years since the first discovery of a Neanderthal fossil; yet very little has since been uncovered about our long-extinct human relatives. The challenge, most scientists say, lies in the few fossilized remains left of our human relatives — skulls may tell us about the shape and size of their brains, but little else about their neurology.
However, some researchers may have uncovered a first step to solving the problem. Using genome-editing, scientists at the University of California were able to grow ‘mini-brains’ with the use of an archaic gene that once belonged to Neanderthals and Denisovans, but not Homo Sapiens.
The created organoids — miniature organs created using stem cells — are by no means a true representation of the real thing, but researchers say they still differ significantly from the brains of modern humans, namely in shape, size and texture. “As soon as we saw the shape of the organoids, we knew that we were on to something,” Alysson Muotri, study leader and neuroscientist at the University of California, San Diego
While the brain tissue of modern humans are typically smooth and spherical, the study, which was published in Science on Feb 11, found that the tissue created with the ancient genes were smaller and had rough, complex surfaces.
“The question here is what makes us human,” Muotri
. “Why are our brains so different from other species including our own extinct relatives?”
In order to ascertain which gene to insert into the organoid, researchers compared modern human genome sequences with the near-complete genomes of two Neanderthals and one Denisovan.
“We asked what is unique about us? We ended up with only 61 protein-coding genes that are different between modern and archaic humans,” Muotri said.
One of those genes was NOVA1 — a gene used to develop the brain’s neurological activity. The version of the gene found in modern humans differs from its ancient variant — which can still be found in some living primates — by a single amino acid base. “The fact that all humans, or nearly all humans, now have this version and not the old one means it gave us a tremendous advantage at certain points during evolution. So the question we have now is, what are these advantages?” Muotri told Nature.
Scientists then used the CRISPR technology to swap the modern version of the gene for its archaic ancestor in stem cells and encourage the cells to grow into the organoids.
The neurons matured much faster in the organoids than in the modern human cells, Muotri observed. “The neurons in the archaic version organoids, we see more activity in the very early stages than the modern human ones. We were definitely not expecting that,” he told CNN.
Why are our brains so different from other species including our own extinct relatives?
He added that he had made similar observation when studying the development of chimpanzee organoids.
“A baby chimpanzee can outsmart a human newborn by far. We need time to nurture our babies until they become independent. We don’t see that in other species. I think what we’re seeing here is something similar,” he said.
Researchers acknowledged that the study’s results come with limitations. For one, the observed changes could simply be due to the result of changing the protein in the tissue, magnifying the effect of many mutations on top of each other. “It’s like Jenga,” Gray Camp, a developmental biologist at the University of Basel in Switzerland, told Nature. “You pull out that amino acid and the brain doesn’t function.”
It’s also important to note that the organoid does not fully represent what a Neanderthal brain looked like and functioned.
However, the technology does open up pathways to study the evolutionary processes shaping humans into what they are today as well as understanding brain evolution across primates.
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