Why are we smarter than Neanderthals
Neanderthals could have fewer neurons in the neocortex than modern humans
Elena Kleshchenko, PCR.news
There is ongoing debate about what the mental abilities of Neanderthals were. Their brains were no smaller than ours, but cognitive abilities depend not only on the size of the brain, but also on the number of neurons, and on the cellular architecture of the neocortex (new cortex) — the structure of the brain that is responsible for higher nervous functions. The human neocortex contains about twice as many neurons as in chimpanzees and bonobos.
A new study points to a possible advantage of modern humans over Neanderthals. The work was carried out by the group of Wieland Hattner, one of the founding directors of the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in collaboration with Svante Paabo, director of the Max Planck Institute for Evolutionary Anthropology, Pauline Wimberger from the Dresden University Clinic and their colleagues.
The enzyme TKTL1 (transcetolase-like protein 1) in modern humans contains arginine at position 317, and the Neanderthal, judging by genomic data, had lysine in this position, as in modern great apes. This is one of the few "Neanderthal" replacements that are practically not found in modern humans. This means that the difference between human and Neanderthal protein variants (the authors of the work designated them modern human TKTL1, or hTKTL1, and archaic TKTL1, aTKTL1) may be important.
TKTL1 is expressed in the progenitor cells of the neocortex of the human embryo, and its expression is highest in the progenitor cells of the frontal lobe. Two types of so-called basal progenitor cells have been characterized in mammals. Basal radial glial cells generate most of the neurons in the developing neocortex of primates and other animals with well-developed brains (for example, ferrets). And in mice, the precursor cells of neurons are mainly represented by the basal intermediate glia - these cells divide once, forming two neurons, unlike basal radial cells, which can produce many neurons. Thus, the basal radial glia provides active growth of the cerebral cortex.
The researchers compared how hTKTL1 and aTKTL1 act on neurogenesis. To do this, they injected a plasmid with the gene of one or another protein variant into the neocortex of mouse embryos, performing electroporation in utero. The number of basal radial glial cells increased under the influence of the modern variant of TKTL1 (interestingly, it did not affect the basal intermediate glia). The Neanderthal version did not cause such an effect. As a result, the brains of mouse embryos that received the "modern" version of TKTL1 contained more neurons. A similar effect was observed on the developing brain of ferrets. Knockout of the TKTL1 gene in human fetal neocortex tissue ex vivo also reduced the number of basal radial glia cells.
The researchers also conducted experiments on organoids — miniature three-dimensional structures that mimic human brain tissue, which are grown from human stem cells. The stem cell genome was edited in such a way that arginine in TKTL1 was replaced by lysine. These mini-brains also contained fewer basal radial glia cells.
"We found that with the Neanderthal—type amino acid, fewer basal radial glial cells were produced in TKTL1 than with the modern-type protein, and, as a result, fewer neurons," says first author Anneline Pinson. "Although we don't know how many neurons were in the Neanderthal brain, we can assume that modern humans have more neurons in the frontal lobe."
The researchers found that the action of hTKTL1 is based on changes in metabolism, in particular, on stimulation of the pentose phosphate pathway, followed by enhanced synthesis of fatty acids. Inhibition of the pentose phosphate pathway suppressed the effect of human TKTL1 in experiments on mice and reduced the number of progenitor cells in the tissues of the neocortex of the embryo. The authors suggest that TKTL1 activates the synthesis of membrane lipids necessary for the growth of basal radial glial cells, thereby stimulating their proliferation and, consequently, increasing the production of neurons.
"It is tempting to assume that this contributed to the development of cognitive abilities of modern humans associated with the frontal lobes," concludes Wieland Hattner, who led the study.
The authors note that although the brain size of a human and a Neanderthal are similar, their shape differs: more rounded in us, more elongated in a Neanderthal. In addition, a modern human has a larger temporal-parietal node — an area of the cortex that is responsible for integrating and processing different types of information and, possibly, for self-awareness. Perhaps these differences were formed by the high activity of hTKTL1, which caused the expansion of the frontal cortex.
Article by Pinson et al. Human TKTL1 implies greater neurogenesis in the frontal neocortex of modern humans than Neandertals is published in the journal Science.
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