Researchers Create Neanderthal "Mini Brains" By Altering A Single Human Gene

Only 61 genetic alterations separate modern humans from Neanderthals. Image Chettaprin.P/

A team of researchers has managed to grow Neanderthal-like mini-brains in a laboratory by swapping a single human gene for an ancient variant. Aside from allowing for a close inspection of the cortical apparatus of our extinct relatives, this incredible experiment also sheds light on the genetic roots of human intelligence.

Outlining their work in the journal Science, the study authors point out that the organoids they produced should not be considered true Neanderthal brains, but are more like blobs of neurons that possess the genetic characteristics of this extinct hominid species.

The researchers began by comparing the sequenced genomes of modern humans and Neanderthals, and identified 61 specific mutations that separate the two species. Of these altered genes, one in particular caught their attention.

Known as neuro-oncological ventral antigen 1 (NOVA1), the gene in question is a master regulator of other genes and plays a central role in the formation of synapses, which are the connections between neurons. More specifically, NOVA1 influences a process called splicing, which is crucial for gene expression.

In humans, altered NOVA1 splicing has been associated with various neurological disorders, highlighting the importance of this gene for neurodevelopment.

The Neanderthal variant of NOVA1 differs from that of modern humans by a single molecular building block, otherwise known as a nucleotide. Nevertheless, swapping one variant for another was found to have dramatic consequences.

To discover this, the researchers used a gene-editing technique called CRISPR in order to alter the genome of human pluripotent stem cells, swapping out their human NOVA1 variant for the Neanderthal form. These stem cells later developed into neurons, forming small organoids of Neanderthal-ized brain tissue.

Even to the naked eye, these mini-brains differed greatly from human organoids, displaying a markedly different shape. Closer inspection revealed that the Neanderthal organoids developed more slowly and had greater surface complexity than those with the modern NOVA1 gene.

The expression of the archaic variant also led to altered synaptic protein interactions and neurotransmitter signaling, and prevented neurons from synchronizing in networks.

Based on these observations, the researchers conclude in the paper that “the human-specific substitution in NOVA1, which became fixed in modern humans after divergence from Neanderthals, may have had functional consequences for our species’ evolution.”

In a statement, study author Dr Alysson Muotri remarked that "it's fascinating to see that a single base-pair alteration in human DNA can change how the brain is wired." 

"We don't know exactly how and when in our evolutionary history that change occurred. But it seems to be significant, and could help explain some of our modern capabilities in social behavior, language, adaptation, creativity and use of technology."

It’s important to note, however, that this study only analyzed the impact of one Neanderthal gene variant, and that there are still 60 more genes to investigate. To understand exactly how a Neanderthal brain looked and functioned, researchers will need to create organoids that possess all of these ancient gene variants.


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