Only ‘1’ mutation may have given rise to the modern human brain

Studies of lab-grown “mini-brains” suggest that a mutation in the brain of our ancestors may have created the modern human mind.How did we develop such advanced cognitive abilities that led to complex language, literature, and engineering? How does the modern human brain differ from the brains of our closest evolutionary relatives, such as Neanderthals and Denisovans? With these and other questions, how we became the people of today is a question that scientists have been trying to answer for a long time.

By reintroducing ancient genes from extinct species into human “minibrains”, scientists are starting to find new clues. (Minibrains are lab-grown clusters of stem cells that organize themselves into tiny versions of the human brain.)

Much of what we know about human evolution comes from studies of ancient fossils and bones. By studying the size and shape of fossilized skulls, we also know that the brains of archaic humans were roughly the same size as modern human skulls, if not larger, and looked like different shapes.

However, although such variations can be associated with different cognitive abilities and functions, fossils alone cannot explain how shapes affect function. Fortunately, recent technological advances point the way to understanding how different we are from our extinct relatives.

How is our brain different from that of ancient humans?

DNA sequencing allows scientists to compare the genes of Neanderthals and Denisovans with those of modern humans. This helps identify differences and similarities by revealing that we share most of our DNA with Neanderthals and Denisovans.

Still, in some regions there are gene variants carried only by modern humans. These human-specific DNA regions may point to features that distinguish our species from our extinct relatives. By understanding how these genes work, we can learn about traits unique to modern humans.

Comparing archaic and modern DNA sequences, studies are detecting differences in genes important for brain function, behavior and development, particularly genes located in cell division and at synapses that transmit electrical nerve impulses between cells. These show that the modern human brain matured more slowly than the Neanderthal brain. Specifically, the development of the orbitofrontal cortex in infants may have changed significantly, but with subtle nuance, since its separation from Neanderthals.

It has long been unclear which evolutionary changes were critical. A team led by Alysson Muotri of the University of California recently published a study in Science Mag that seeks an answer to this question.

They did this by growing mini-brains from skin-derived stem cells (known as organoids). Brain organoids are not conscious like ours; It works very simply and cannot reach sizes larger than about five or six millimeters due to the lack of blood supply. But it can emit brain waves and create relatively complex neural networks that respond to light.

Using Nobel-winning CRISPR-Cas9 technology, known as “genetic scissors,” that allows precise editing and manipulation of genes, the team added an extinct version of a gene related to brain development to the organoids. We knew this ancient version was present in Neanderthals and Denisovans. A mutation later changed the gene into the current version carried by modern humans.

The engineered organoids showed several differences. They expanded more slowly than human organoids and changed the formation of connections between neurons. They were also smaller than smooth and spherical modern human organoids and had rough, complex surfaces.

What does the study tell us?

The study identified 61 genes that differed between modern and archaic humans. One of these genes is NOVA1, which has an important role in regulating the activity of other genes during early brain development; It also plays a role in synapse formation.

The altered activity of NOVA1 was found to cause neurological disorders such as microcephaly, seizures, severe developmental delay, and a genetic disorder called familial dysautonomia, suggesting that this is important for normal human brain function.

The version that modern people carry differs in a single letter of the code. This change causes the NOVA1 protein to have a different composition and possibly a different activity.

Interestingly, when analyzing organoids, the scientists discovered that the archaic NOVA1 gene changed the activity of 277 other genes; They play a role in forming synapses and connections between most brain cells.

As a result, mini-brains had a different cell network than modern humans. This means that the mutation in NOVA1 causes significant changes in our brain. A change in a single letter of the DNA code likely triggered a new brain function in modern humans. What we don’t know is exactly how it happened.

The team says they will follow up with the fascinating findings by investigating the other 60 genes in more detail to see what happens when you change each or a combination of several.

While it is undoubtedly an interesting area of ​​research where organoids provide important information about the brains of these ancient species, we are still at the beginning. Manipulation of a single gene cannot capture true Neanderthal and Denisovan genetics. But it could still help scientists understand how some human-specific genes work.

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