Neanderthal vs. modern humans: Slow and steady wins the brain game

Our closest human relatives are Neanderthals (split from modern humans at least 500,000 years ago) and their Asian relatives the Denisovans (split from modern humans around 800,000 years ago). The differences between Homo sapiens and these other groups are encoded in changes to the amino acids which are the building blocks of proteins in our cells and tissues.

About 100 amino acids changed in modern humans after these splits and spread throughout almost all of us. The biological significance of these changes, however, is largely unknown.

Researchers in Germany looked at changes to six of these amino acids occurring in three proteins. These amino acids play key roles in the distribution of chromosomes to the two daughter cells during cell division.

Since the remarkable work done in sequencing the Neanderthal genome this study furthers our understanding of the subtle differences between these ancient humans and modern humans. It may also shed some light on the evolutionary advantages that eventually saw modern humans outlive Neanderthals and Denisovans.

Authored by researchers from the Max Planck Institute for Evolutionary Anthropology in, the results are published in Science Advances.

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To investigate how these six changes impact brain development, the scientists introduced the amino acids from modern human variants into mice. Interestingly, in those six amino acid positions, mice are identical to Neanderthals. That makes mice brains perfect for testing what happens when these amino acids are changed.

Lead author of the study, Felipe Mora-Bermúdez, says the changes result in more accurate transfer of genetic data in cell division. “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, and this results in fewer errors when the chromosomes are distributed to the daughter cells of the neural stem cells, just like in modern humans.”

The team also checked to see if the opposite would be true. If they replaced the modern human amino acids with those present in Neanderthals, would they see faster and less accurate mitosis?

They introduced the ancestral amino acids in human brain organoids. Organoids are miniature organ-like structures that can be grown from human stem cells in the lab which mimic aspects of early human brain development.

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

“In this case, the metaphase became shorter and we found more chromosome distribution errors.” According to Mora-Bermúdez, this shows that those three modern human amino acid changes in the proteins are responsible for the fewer chromosome distribution mistakes seen in modern humans compared to Neanderthal and chimpanzees. He adds that “having mistakes in the number of chromosomes is usually 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 findings also suggest that brain function in Neanderthals may have been more affected by chromosome errors than that of modern humans,” adds co-author Wieland Huttner.

Svante Pääbo, who also co-supervised the study, adds that “future studies are needed to investigate whether the decreased error rate affects modern human traits related to brain function.”

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