Scientists uncover a greater neuron production in the frontal lobe during brain development in modern humans than Neanderthals due to the change of a single amino acid in the protein TKTL1. What makes modern humans unique? It is a question that has long been a driving force for researchers. There
The scientists focus on one of these proteins that presents a single amino acid change in essentially all modern humans compared to Neanderthals, the protein transketolase-like 1 . Specifically, in modern humans, TKTL1 contains an arginine at the sequence position in question, whereas in Neanderthal TKTL1 it is the related amino acid lysine. In the fetal human neocortex, TKTL1 is found in neocortical progenitor cells, the cells from which all cortical neurons derive.
“We found that with the Neanderthal-type of 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. “This shows us that even though we do not 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 highest, than Neanderthals.
The researchers also discovered that modern human TKTL1 acts through changes in metabolism. Specifically, stimulation of the pentose phosphate pathway followed by increased fatty acid synthesis. In this way, modern human TKTL1 is thought to increase the synthesis of certain membrane lipids needed to generate the long process of basal radial glial cells that stimulates their proliferation and, therefore, increases neuron production.
“This study implies that the production of neurons in the neocortex during fetal development is greater in modern humans than it was in Neanderthals, in particular 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.”
Reference: “Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals” by 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 and Wieland B. Huttner, 9 Sepetember 2022,
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