Development of stem cells between modern humans and Neanderthals

To investigate the significance of these six changes for neocortex development, scientists first introduced the modern human variants in mice. Mice are identical to Neanderthals at those six amino acid positions, so these changes made them a model for the developing modern human brain.

Felipe Mora-Bermúdez, the lead author of the study, describes the discovery: "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."

To check if the Neanderthal set of amino acids has the opposite effect, the researchers then introduced the ancestral amino acids in human brain organoids – miniature organ-like structures that can be grown from human stem cells in cell culture dishes in the lab and that mimic aspect of early human brain development.

"In this case, metaphase became shorter and we found more chromosome distribution errors." According to Mora-Bermúdez, these three modern human amino acid changes in the proteins known as KIF18a and KNL1 are responsible for the fewer chromosome distribution mistakes seen in modern humans as compared to Neanderthal models 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 modern humans," summarizes Wieland Huttner, who co-supervised the study.

Ref:

Felipe Mora-Bermúdez et. al, Longer metaphase and fewer chromosome segregation errors in modern human than Neanderthal brain development, Science Advances, 29-Jul-2022, 10.1126/sciadv.abn7702