Modern humans generate more brain neurons than Neanderthals

Image from the documentary “The Neanderthal Genetic Code”.

Science | biology

Researchers at the Max Planck Institute in Germany discover that the finding is due to a single amino acid change in the TKTL1 protein.

Although Neanderthals and modern humans developed a similarly sized brain and neocortex (a part of the brain that is crucial for many cognitive abilities), it is not clear whether this implies a similar number of neurons in each other, a key factor in the development of cognitive skills. Now, researchers at the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany, in collaboration with Svante Pääbo, director of the Max Planck Institute for Evolutionary Anthropology in Leipzig, and Pauline Wimberger of the Dresden University Hospital They have found a possible answer.

By comparing the proteins of modern humans with our extinct relatives, the Neanderthals and Denisovans, scientists have been able to verify that the minute differences between their amino acids, the building blocks of proteins. For this study, they took protein transketolase 1 (TKTL1) as a reference, which consists of 596 amino acids and only one of them is different from those of the Neanderthal variant of the TKTL1 protein.

It is known that TKTL1 participates in the formation of embryonic cells called radial glia, from which neurons and other essential cells of the most modern cerebral cortex, called neocortex, are formed, responsible for abstract thought and reasoning of the human being current. The activity of the TKTL1 protein is particularly high in the frontal lobe of the brain of the human fetus during pregnancy, so the researchers believe that this difference in amino acids is responsible for modern humans having a greater production of neurons in the lobe. frontal and, as a consequence, higher cognitive abilities.

Specifically, the difference is that in modern man the amino acid arginine replaces the amino acid lysine in Neanderthal man. To test this, the researchers introduced the modern human variant of TKTL1 and the Neanderthal variant into two groups of mouse embryos. This allowed them to see how basal radial glial cells, thought to be the driving force for a larger brain, increased with the modern variant, but not with the ancient one. As a consequence, the brains of mouse embryos with modern human TKTL1 contained more neurons.

Following this finding, the researchers went a step further and explored the relevance of these effects for the development of our brain. To do this, they replaced the arginine in modern human TKTL1 with the lysine in Neanderthal TKTL1 using human brain organoids, miniature structures similar to real organs that can be grown from human stem cells in the laboratory, and which mimic aspects of the brain. early human brain development.

"We found that with the Neanderthal-type amino acid in TKTL1, fewer basal radial glial cells were produced than with the modern human type and, as a consequence, also fewer neurons," says Anneline Pinson, lead author of the study. "This shows us that although we don't know how many neurons the Neanderthal brain had, we can assume that modern humans have more neurons in the frontal lobe of the brain, where TKTL1 activity is higher than Neanderthals." "It is tempting to speculate that this promoted modern human cognitive abilities associated with the frontal lobe," adds Wieland Huttner, who supervised the study.

Voices for and against

The researchers also found that modern human TKTL1 acts through changes in metabolism, specifically a stimulation of the pentose phosphate pathway, which is important because it protects against cellular oxidative damage, and is involved in sugar metabolism and protein synthesis. nucleotides (precursors of DNA and RNA), which gives an idea of ​​its importance in humans.

This research is an important step in our understanding of what differences may have given us an advantage over Neanderthals, intellectual or otherwise, and also shows that small changes at the genomic level can have large consequences", says Víctor Borrell Franco, researcher CSIC scientist at the Institute of Neurosciences (Alicante), who did not participate in the study, in statements collected by the Science Media Center Spain (SMC).

Emiliano Bruner, a researcher at the National Center for Research on Human Evolution (CENIEH), who did not participate in the study, is less hopeful and optimistic, considering that the brain's cognitive process is so complex and conditioned by so many variables that limiting all this function at the expense of a minimum genetic modification is very doubtful, especially when there is an extensive literature that analyzes and reveals the cognitive differences between the two species. “I find it very reductive to reach such important conclusions only from a single gene and cell culture or expression experiment,” he told the SMC.