Brain development differs between Neanderthals and modern humans

Left side: Microscopy image of the chromosomes (in cyan) of a modern human neural stem cell from the neocortex during cell division. Right side: same type of image, but of a cell where three amino acids of the two proteins KIF18a and KNL1, involved in the separation of chromosomes, have been changed from modern humans to Neanderthal variants. These “neandertalized” cells show twice as many chromosomal separation errors (red arrow). Credit: Felipe Mora-Bermúdez / MPI-CBG

Neanderthals are the closest relatives of 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 outer layer of the brain, is unique 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 from 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 now discovered that neural stem cells – the cells from which developing neurons derive from the neocortex – spend more time preparing their chromosomes for division in modern humans than in Neanderthals. This results in 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 Denisovans, their Asian relatives, around 100 amino acids, the building blocks of proteins in cells and tissues, changed in modern humans and became spread to almost all modern humans. The biological significance of these changes is largely unknown. However, six 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 the development of the neocortex, the scientists first introduced the modern human variants into 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 phase where chromosomes are prepared 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. human cells in cell culture dishes in the laboratory and which mimic aspects 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 KIF18a 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 disorders like trisomies and cancer.”

“Our study implies that some aspects of modern human brain evolution and function may be independent of brain size since Neanderthals and modern humans have similar sized brains. The results also suggest that brain function in Neanderthals might have been more affected by chromosomal errors than that of modern humans,” says Wieland Huttner, who co-supervised the study. Svante Pääbo, who also co-supervised the study, adds that “future Studies are needed to determine if the decreased error rate affects modern human traits related to brain function.”

Scientists Discover New Feature That Distinguishes Modern Humans From Neanderthals

More information:
Felipe Mora-Bermúdez et al, Longer metaphase and fewer chromosome segregation errors in modern humans than Neanderthal brain development, Scientists progress (2022). DOI: 10.1126/sciadv.abn7702.

Provided by the Max Planck Society

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