What makes our mind so special? A study has now shown that modern humans developed more nerve cells than Neanderthals in the brain thanks to a modified protein: Through studies on mice and cultured "mini brains", researchers were able to show that the human protein TKTL1, in contrast to the Neanderthal version, leads to a increased formation of neurons in the developing frontal lobe of the neocortex, which is critical for many cognitive abilities.
We comprehend, plan, and cooperate in a way that no other living creature can cunningly do: The enormous capacity of the brain has become the key to our species' success. But what underlies the development of modern man's cognitive superiority? Basically, it seems clear that it was associated with an increase in brain size and thus an increased formation of nerve cells in the course of our evolutionary history. An interesting question is to what extent modern humans' brains differed from those of their closest relatives - Neanderthals.
Both species had brains of similar size, and recent research suggests that Neanderthals' cognitive abilities weren't as different from modern humans, at least not as much as previously thought. However, there may have been certain differences. It was previously unclear to what extent the comparable size of the brain also means a similar number of nerve cells. The researchers led by Wieland Huttner from the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden have now investigated this question. As a basis, they used the fact that the genetic material of the Neanderthals is known from the analysis of fossil DNA and thus also to what extent they formed different proteins than modern humans.
On the trail of the meaning of a difference
Basically, it can be stated that there are only very few proteins that differ between the two types in the sequence of the amino acids - their building blocks. But as the team of scientists reports, there is one striking exception: the protein transketolase-like 1 (TKTL1) differs in us and in Neanderthals by one component: in modern humans, the TKTL1 protein has the amino acid arginine at a specific sequence position, while there the related substance lysine is found in Neanderthal TKTL1. An interesting aspect was that it is already known that TKTL1 is formed in the fetal human neocortex in progenitor cells from which all cortical nerve cells are derived.
As part of their study, the scientists have now examined the importance of the tiny difference between the two TKTL1 versions for the development of the neocortex. Mice were initially used as a model: the researchers used genetic engineering methods to ensure the formation of TKTL1 in the neocortex of rodent embryos. One group was the human version of the protein, while another group was the Neanderthal version. They found that the human variant of TKTL1 produced more basal radial glial cells—the type of neocortical progenitor cells thought to be the driving force behind a larger brain. With the Neanderthal version, however, these cells did not multiply. As a result, comparatively more neurons developed in the brains of the mouse embryos with the human TKTL1.
Fewer nerve cells with the Neanderthal protein
The researchers then went on to a more human model system: They carried out experiments with so-called brain organoids. These are organ-like miniature structures made of nerve tissue that are grown in the laboratory from human stem cells. In some of these brain organoids, the scientists replaced the arginine in the modern human TKTL1 protein with lysine, which is characteristic of Neanderthal TKTL1. They then examined how this "Neandertalization" affected the development of human "mini-brains".
"We found that with the Neanderthal-type of the amino acid in TKTL1, fewer basal radial glial cells were produced than with the modern-human type, and consequently fewer neurons," reports first author Anneline Pinson from the MPI-CBG. The research team also gained indications of how TKTL1 affects modern humans: it apparently causes changes in metabolism, in particular by stimulating the so-called pentose phosphate pathway, followed by increased fatty acid synthesis. Ultimately, the protein probably increases the synthesis of certain membrane lipids. These in turn play a role in the proliferation of basal radial glial cells, which lead to increased nerve cell production, the researchers explain.
"Based on our results, one can assume that the formation of neurons in the neocortex during fetal development is greater in modern humans than in Neanderthals, mainly in the frontal lobe," Huttner summarizes the results. "It is quite conceivable that this has promoted the cognitive abilities of modern humans, which are based on the frontal lobe," says the scientist.
Source: Max Planck Institute for Molecular Cell Biology and Genetics, Article: Science, doi: 10.1126/science.abl6422