THE TKTL1 PROTEIN

The mutation in question leads to a single amino acid change in a protein called TKTL1. Previous studies have shown that this mutation is present in almost everyone living todaybut not in older humans, such as Neanderthals and the Denisovansnor in other primates.

The TKTL1 protein is also known to be produced in progenitor cells that give rise to the neocortex (the outer layer of the brain involved in conscious thought and language). suggesting that she may have helped shape the brain modern humans, in particular by increasing the synthesis of certain membrane molecules necessary to increase the production of neurons in the frontal lobe.

As part of work published in the journal Science, Anneline Pinson and her colleagues at the Max Planck Institute sought to precisely determine its impact, by injecting the modern human TKTL1 protein into the brains of mouse embryos and ferrets. They also cultured brain organoids from human cells, some of which were modified to produce the older version of TKTL1, present in Neanderthals.

These experiments showed that the mutation increased the number of neocortical progenitor cells, called radial basal glia, involving a higher number of neurons in this part of the brain. According to Wieland Huttner, co-author of the study, the result would have been “an increase in the size of the neocortex, the density of neurons inside, or even both”.

SKULLS OF A SIMILAR SIZE BUT DIFFERENT SHAPE

The study of the skulls suggests that the brains of modern humans and Neanderthals were similar in size, but different in shape, with Neanderthals having more elongated brains. According to the researchers, it is possible that this difference in shape is also due to the mutation.

“Even though we don’t know how many neurons the Neanderthal brain had, we can assume that the frontal lobe of modern humans, where TKTL1 activity is highest, harbors more of them,” Pinson points out.

So could we make people smarter by modifying genes to increase the number of basal radial glial cells? “I don’t know if we could do it,” says the researcher. “Having more neurons can also have disadvantages. »

Why have modern human brains stopped growing?

In the collective imagination, as in science fiction, an oversized skull and brain is a sign of extraordinary cognitive abilities. This is what happened in human history: among hominins, our ancestors, there was an increase in brain size over time. This is the case for us, the Sapiens, but also for the Neanderthals, whose brain is sometimes larger than that of modern humans. Above all, our brains have not increased in size in the last 300,000 years. How did it grow and improve without increasing in size?

To answer this question, the researchers studied gene variants, gene versions involved in brain development and which are different in Neanderthals and modern humans, in particular that of the TK-TL1 gene. The scientists used organoids, tiny laboratory brains into which different versions of a gene could be implanted. It turns out that the Sapiens version produces more neurons and more connectivity between neurons… in the neocortex of the frontal lobe than the Neanderthal version! And we know that this frontal lobe is decisive for certain cognitive abilities such as language, decision-making or creativity. The modern human, Sapiens, would therefore have followed another path of improvement than the endless increase in brain size.

Alexandra Delbot interviews Jean Jacques Hublinpaleoanthropologist, holder of the paleoanthropology chair at the Collège de France, emeritus professor at the Max Planck Institute for Evolutionary Anthropology in Leipzig.

Differences revealed in human and Neanderthal brains

Now, an interesting study published on September 8 has revealed a possible difference that could have given modern humans, or sapiens, a cognitive advantage over Neanderthals, the Stone Age hominids that lived in Europe and parts of Europe. Asia before their extinction around 40,000 years ago. . .

Scientists at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, claim to have identified a genetic mutation that led to faster formation of neurons in the brains of sapiens. The primitive variant of the gene in question, known as TKTL1, differs from the modern human variant by just one amino acid.

“We have identified a gene that helps make us human,” said study author Welland Huttner, professor and director emeritus of the institute.

When two copies of the gene were inserted into mouse embryos, the research team discovered that a modern human variant of the gene resulted in an increase in a specific type of cell that creates neurons in the neocortex region of the brain. . The scientists also tested the two genetic variants in rodent embryos and brain tissue grown in the lab from human stem cells, called organoids, with similar results.

The team concluded that this ability to produce more neurons likely gave sapiens a cognitive advantage unrelated to overall brain size, suggesting that modern humans have “a more modern cortex to work with than ancient Neanderthals,” according to the study published in the journal. Science.

“This shows that although we don’t know how many neurons a Neanderthal brain has, we can assume that modern humans have more neurons in the frontal lobe of the brain, where TKTL1 activity is greater than of Neanderthals,” Huttner said. Explain.

He added: “There has been some debate as to whether the Neanderthals’ frontal lobe was as large as that of modern humans. »

“But we don’t need to worry about that because (from this research) we know that modern humans should have more neurons in the frontal lobe…and we think that’s a benefit of cognitive abilities. »

“Premature” discovery

Alison Muotri, professor and director of the stem cell program and center for archeology at the University of California, San Diego, said that while animal experiments revealed a “significant difference” in neuron production, the difference was more subtle in the organelles. He did not participate in the research.

“This was only done in one cell line, and since we have so much versatility with this protocol for brain organoids, it would be ideal to repeat the experiments with a second cell line,” he said per E-mail.

It’s also possible that the older version of the TKTL1 gene isn’t unique to Neanderthals, Muotri noted. Most genomic databases have focused on Western Europeans, and humans from other parts of the world likely shared the Neanderthal version of this gene.

“I think it’s too early to suggest differences between Neanderthals and modern human cognition,” he said.

Archaeological finds in recent years have indicated that Neanderthals were more complex than popular culture depictions of savage cavemen suggest. Our ancient parents knew how to survive in cold and hot climates and used complex tools. they also do filming and artistic creation.

Study co-author and geneticist Svante Pääbo, director of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, was the first to extract, sequence and analyze ancient DNA from Neanderthal bones.

His work led to the discovery in 2010: Early humans intermarried with Neanderthals. The scientists then compared the Neanderthal genome with the genetic archive of humans alive today to see how our genes overlap and differ: TKTL1 is just one of dozens of specific genetic variations, while some common genes may have implications for human health.

Neanderthals disappeared 40,000 years ago, but thanks to their DNA they are still among us

They were very successful and spread in an area from the Mediterranean to Siberia. They hunted big game, gathered plants, gathered mushrooms and seafood, controlled fire for cooking, made composite tools, made clothing from animal skins, made beads from shells, and engraved symbols on the walls of caves. They cared for their young, old, and sick, created shelters for protection, lived through harsh winters and hot summers, and buried their dead.

Neanderthals encountered our ancestors many times over tens of thousands of years, and the two species shared the continent of Europe for at least 14,000 years. They even mated. The most significant difference between Neanderthals and us is that they died out around 40,000 years ago.

The precise cause of their disappearance still eludes us, but we believe it is likely the result of a combination of factors. First of all, the climate of the last ice age was very variable, going from cold to hot and vice versa, which put pressure on animal and plant food sources.

Then, there have never been so many Neanderthals, the global population never exceeding tens of thousands of individuals.