Researchers studying the developmental differences between Neanderthals and modern humans have found that time makes the difference. According to their study, published in the journal Science Advances, stem cells in the developing brain of modern humans take longer to divide and they make fewer errors in distributing their chromosomes to their daughter cells, compared to Neanderthals.
After the ancestors of modern humans diverged from those of Neanderthals and Denisovans, their Asian relatives, about a hundred amino acids, the building blocks of proteins in cells and tissues, changed in modern humans and spread to almost all of them.
The biological significance of these changes is largely unknown, but six of those amino acid changes occurred in three proteins they play a key role in distributing chromosomes, the carriers of genetic information, to the two daughter cells during cell division.
To investigate the importance of these six changes in the development of the neocortex, the scientists first introduced the modern human variants into mice. Mice are identical to Neanderthals at those six amino acid positionsso these changes made them a model for the development of the modern human brain.
Felipe Mora-Bermúdez, from the Max Planck Institute for Molecular Cell Biology and Genetics, in Germany, and lead author of the study, explains that they found that “three modern human amino acids in two of the proteins cause a longer metaphase, a phase in which Chromosomes prepare for cell division, and this results in fewer errors when chromosomes are distributed to neural stem cell daughter cells, just as in modern humans.”
To test whether the Neanderthal amino acid pool has the opposite effect, the researchers then introduced the ancestral amino acids into human brain organoids – miniature organ-like structures that can grow from human stem cells in cell culture dishes in the laboratory and mimic aspects of early human brain development.
“In this case, the metaphase was shortened and we found more chromosomal distribution errors,” Mora-Bermúdez points out, adding that this shows that these three amino acid changes in modern humans in proteins known as KIF18a and KNL1 are responsible for the lower chromosomal distribution errors observed in modern humans compared to Neanderthal models and chimpanzees.
Add that “Having errors in the number of chromosomes is usually not a good idea for cells, as can be seen in disorders such as trisomies and cancer.”
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“Our study implies that some aspects of modern human brain evolution and function may be independent of brain size, as Neanderthals and modern humans have similarly sized brains. The findings also suggest that Neanderthal brain function may have been more affected by chromosomal errors than that of modern humans,” summarizes Wieland Huttner, who co-supervised the study.
Svante Pääbo, who also co-supervised the study, adds that “future studies are needed to investigate whether the error rate decline affects modern human traits related to brain function.”