A single amino acid change in transketolase-like protein 1 (TKTL1) may have given modern humans an advantage over older contemporaries such as Neanderthals by allowing greater neocortical neurogenesis, researchers report.
According to the authors, this genetic change could contribute to the cognitive differences involved between modern and extinct archaic humans. The outer region of the cerebral cortex, the neocortex, is an evolutionarily advanced brain structure responsible for cognitive abilities. This structure is clearly large and complex in humans, which is widely thought to endow our species with unique and extraordinary cognitive abilities.
However, the evolution of the neocortex in hominids is not well understood, and although fossil evidence indicates that Neanderthal brains were similar in size to those of modern humans, it remains unknown how they might have differed in function or structure. Previous studies have shown that differences in neural progenitor cell populations can result in the variable size and shape of neocortices between living species. Anneline Pinson and colleagues compared genomic sequences of modern humans with Neanderthals and other apes and discovered a unique amino acid substitution encoded in the TKTL1 gene of modern humans. When placed in organoids or overexpressed in mouse and ferret brains, Pinson et al. found that the human variant TKTL1 (hTKTL1) drove the generation of basal radial glia (bRG) neuroprogenitors more than the archaic variant, leading to the proliferation of neocortical neurons.
Disruption of hTKTL1 expression or replacement of hTKTL1 with the archaic variant in human fetal neocortical tissue and brain organoids resulted in reduced generation of bRGs and neurons. “Together, these observations pave the way for uncovering more specific evolutionary changes that shaped the modern human brain and may also help us predict the next steps in its evolution,” Brigitte Malgrange and Laurent Nguyen write in a related perspective.
Source:
American Association for the Advancement of Science (AAAS)
Journal reference:
Pinson, A., et al. (2022) Human TKTL1 implicates greater neurogenesis in the frontal neocortex of modern humans than Neanderthals. science doi.org/10.1126/science.abl6422.