Brain development differs between Neanderthals and modern humans

Neanderthals are the closest parents to modern humans. Comparisons with them can therefore provide fascinating insights into what makes today’s humans unique, for example with regard to brain development. The neocortex, the largest part of the brain’s outer layer, is distinctive to mammals and crucial for many cognitive abilities. It expanded significantly during human evolution in the ancestral species of Neanderthals and modern humans, giving Neanderthals and modern humans brains of similar sizes. However, almost nothing is known about how modern human and Neanderthal brains may have differed in development and function.

Researchers at the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden and the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig have just discovered that cells Neural stems — the cells from which neurons in the system develop a neocortical shunt — spend longer preparing their chromosomes for division in modern humans than in Neanderthals. This leads to fewer errors when chromosomes are distributed to daughter cells in modern humans than in Neanderthals or chimpanzees, and could have consequences for brain development and function. This study shows cellular differences in brain development between modern humans and Neanderthals.

After the ancestors of modern humans split from those of Neanderthals and from the Denisovans, their Asian dad and mom, one hundred amino acids, the building blocks of proteins in cells and tissues, changed in modern humans and spread to nearly all modern humans. The biological significance of these changes is largely unknown. However, 6 of these amino acid changes occurred in three proteins that play a key role in delivering chromosomes, the carriers of genetic information, to the two daughter cells during cell division.

The effects of modern human variants on brain development

To study the importance of these six changes for development of the neocortex, scientists first introduced modern human variants in mice. Mice are identical to Neanderthals at these six amino acid positions, so these changes have made them a model for modern human brain development. Felipe Mora-Bermúdez, the study’s lead author, describes the finding: “We found that three modern human amino acids in two of the proteins cause a longer metaphase, a period when chromosomes are primed for cell division. , resulting in fewer errors when chromosomes are delivered to daughter cells of neural stem cells, just like in modern humans.” To test whether the Neanderthal set of amino acids has the opposite effect, the researchers then introduced the ancestral amino acids into human brain organoids – miniature organ-like structures that can be grown from stem cells. cells in cell society dishes in the laboratory and which mimic elements of early human brain development. “In this case, the metaphase became shorter and we found more errors in chromosomal distribution.” According to Mora-Bermúdez, this shows that these three modern human amino acid changes in proteins known as KIFa and KNL1 are responsible for the fewest chromosome distribution errors seen in modern humans compared to Neanderthal models and chimpanzees. He adds that “having errors in the number of chromosomes is generally not a good idea for cells, as can be seen in conditions like trisomies and cancer”.

“Our study implies that some features of modern human brain evolution and function may be independent of brain size since Neanderthals and modern humans have similar sized brains. The findings also suggest that brain function in Neanderthals may have been more affected by chromosomal errors than that. modern man”, summarizes Wieland Huttner, who co-directed the study. Svante Pääbo, who also co-supervised the study, adds that “future studies are needed to determine whether the decrease in error rate affects modern human features related to brain function”.

Amino AcidCellBrainChromosomeNeanderthal ManHomo SapiensNeocortexProtein

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