What makes modern humans so unique? An international team of researchers, led by Anneline Pinson, from the Max Planck Institute for Molecular Cellular Biology and Genetics, and with collaborators such as the scientist Svante Paäbo, who managed to sequence the genome of a Neanderthal for the first time in 2010, has discovered that modern humans have a genetic mutation that drives the growth of neurons in the neocortex of the brain, a region of the brain associated with higher intelligence, and that this would have given us the advantage to make more neurons than Neanderthals, who did not have this mutation .
A slight but important difference
The increase in brain size and neuron production during brain development are considered important factors for the increase in cognitive abilities that occurred during human evolution.
The identified mutation results in a single amino acid change in a protein called TKTL1 that drives the growth of neurons in the neocortex, a brain region associated with higher intelligence. Previous research has shown that this mutation is present in almost all people alive today, but not in the earliest humans, such as Neanderthals and Denisovans, or in other primates, so it likely makes us smarter. say the researchers in their study published in the journal Science .
Scientists have shown that the modern human variant of the TKTL1 protein, which differs by a single amino acid from the Neanderthal variant, increases a type of brain progenitor cells, called radial glial cells, in the modern human brain. These basal cells generate most of the neurons in the developing neocortex, a part of the brain that is crucial for many cognitive abilities. Because these cells are responsible for producing new neurons, their increase, in turn, produces a much larger number of neuron cells in the brains of modern humans.
This suggests that our species produced more neurons during our development than Neanderthals did during theirs some 130,000 to 40,000 years ago. Our increased neuronal output brings scientists one step closer to understanding why our species is so different.
To find out what difference the mutation makes, Pinson, Huttner and their colleagues added the modern human TKTL1 protein to the brains of mouse and ferret embryos. They also grew brain organoids from human cells, some of which were gene-edited to produce the earlier version of TKTL1. These studies show that the mutation increases the number of neocortex progenitor cells, called basal radial glia, resulting in increased numbers of neurons in the neocortex.
“This study implies that the production of neurons in the neocortex during fetal development is greater in modern humans than in Neanderthals, particularly in the frontal lobe,” summarizes Wieland Huttner, who supervised the study. “It is tempting to speculate that this promoted modern human cognitive abilities associated with the frontal lobe.”
Studies of the skulls suggest that the brains of modern humans and Neanderthals were similar in size, but different in shape (Neanderthals were longer). The researchers speculate that, although we do not know the number of neurons in the Neanderthal brain, it is possible that this difference in shape is due precisely to the genetic mutation.
Referencia:Anneline Pinson, Lei Xing, Takashi Namba, Nereo Kalebic, Jula Peters, Christina Eugster Oegema, Sofia Traikov, Katrin Reppe, Stephan Riesenberg, Tomislav Maricic, Razvan Derihaci, Pauline Wimberger, Svante Pääbo, Wieland B. Huttner. Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals. Science, 2022; 377 (6611) DOI: 10.1126/science.abl6422
Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment. Science 12 Feb 2021 Vol 371, Issue 6530 DOI: 10.1126/science.aax2537