The change of a single amino acid in a single protein, TKTL1, could have given modern humans a decisive advantage over their contemporaries, the Neanderthals, by allowing the formation of a greater number of neurons in the cerebral neocortex. That is the extraordinary conclusion reached by an extensive international team of researchers, led by Anneline Pinson, from the Max Planck Institute for Molecular Cellular Biology and Genetics, and in which they have collaborated, among others, Svante Paäbo, who in 2010 achieved together with his team to sequence the genome of a Neanderthal for the first time.
According to the researchers, this small genetic change contributed decisively to the cognitive differences between the first humans of our species and other human variants that eventually became extinct. The study is published today in the journal ‘Science’.
The outer region of the cerebral cortex, the neocortex, is directly responsible for cognitive abilities. In humans, this structure is large and complex, which is believed to endow our species with unique and extraordinary abilities. However, the evolution of the neocortex in hominids is still poorly understood, and despite fossil evidence indicating that Neanderthal brains were similar in size to modern humans, it is unknown what their differences might have been. in terms of functions and structure.
Previous studies had already shown that the different number of progenitor cells of neurons in different populations result in different shapes and sizes of the neocortex of living species. And now Anneline Pinson and her colleagues have compared genome sequences from modern humans with those from Neanderthals and apes and discovered a single amino acid substitution, encoded in the TKTL1 gene, that occurs only in modern humans.
a single amino acid
By placing the modified amino acid in an organoid (a simplified, miniature version of an organ), or by overexpressing it in the brains of mice and ferrets, the researchers found that the modern human variant of TKTL1 generated more neuroprogenitors from radial glia basal than variants of the gene from archaic humans, resulting in the production of much larger numbers of neocortical neurons.
On the contrary, when the expression of the amino acid was interrupted or replaced by its archaic variant in neocortical tissue of human fetuses or cerebral organoids, the production of neurons was drastically reduced. Together, these observations pave the way for discovering the specific evolutionary changes that shaped the modern human brain, setting it apart from that of all its congeners.
frontal lobe
The relevance of these findings is that they demonstrate the critical importance of this single amino acid change between Neanderthals and modern humans in the embryonic development of their cerebral cortex, leading to much greater progenitor cell proliferation and neurogenesis in modern humans. . Given that TKTL1 is expressed to a greater extent in the frontal lobe of modern humans, the results of this study further suggest that this small genetic change may have been key to the characteristic expansion of the frontal lobe in modern humans compared to humans. ancient humans and other non-human primates, taking on their typical modern form.
The study, of course, has not been indifferent, and has already provoked different reactions in the scientific community. As Emiliano Bruner, from the National Center for Research on Human Evolution (CENIEH), explained to SMC Spain, “the brain is an incredibly complex organ and the cognitive process is much more so, because it also encompasses environmental factors of all kinds. It seems to me very reductionist to reach such important conclusions only as a result of a single gene and a cell culture or expression experiment ».