Neanderthals are the closest relatives of modern humans. So comparisons with them can provide fascinating insights into what makes present-day humans unique, for example in terms of brain evolution. The neocortex, the largest part of the outermost layer of the brain, is unique to mammals and is essential for many cognitive abilities. It expanded greatly during human evolution in the ancestral species to both Neanderthals and modern humans, resulting in both Neanderthals and modern humans having brains of the same sizes. However, almost nothing is known about how modern human and Neanderthal brains differed in terms of their evolution and function.
Researchers from the Max Planck Institute for Molecular Cell Biology and Genetics (MPI-CBG) in Dresden and the Max Planck Institute for Developmental Anthropology (MPI-EVA) in Leipzig have now discovered that neural stem cells – the cells from which neurons emerge in morphogenesis. Neocortical derivative – they spend more time preparing their chromosomes for division in modern humans than they do 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 how the brain develops and functions. This study shows the cellular differences in brain development between modern humans and Neanderthals.
After the ancestors of modern humans separated from the ancestors 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 modern humans. The biological significance of these changes is largely unknown. However, six of those amino acid changes occurred in three proteins that play key roles in the distribution of chromosomes, the carriers of genetic information, into two daughter cells during cell division.
Effects of modern human variables on brain development
To investigate the significance of these six changes to the development of the neocortex, scientists have introduced for the first time modern human variants in mice. Mice are identical to Neanderthals in those six amino acid positions, so these changes made them a model for the developing modern human brain. Felipe Mora-Bermúdez, lead author of the study, describes the discovery: “We found that three modern human amino acids in two proteins cause a longer anaphase, a phase in which chromosomes are prepared for cell division, and this results in fewer errors when chromosomes are distributed to the daughter cells of cells neural stem, just as in modern humans.” To check whether the Neanderthal’s amino acid group had the opposite effect, the researchers then introduced the ancestral amino acids into human brain organoids — miniature organ-like structures that can be grown from human stem cells in cell culture dishes in vitro that mimic aspects of early human brain development. “In this case, the metaphase got shorter and we found more chromosomal distribution errors.” According to Mora-Bermúdez, this shows that those recent changes in the three human amino acids in proteins known as KIF18a and KNL1 are responsible for the fewer chromosomal distribution errors seen in modern humans than in the Neanderthal and chimpanzee models. He adds that “the presence of errors in the number of chromosomes is usually not a good idea for cells, as can be seen in disorders such as trisomy and cancer.”
“Our study suggests that some aspects of modern human brain development and function may be independent of brain size because Neanderthals and modern humans have similarly sized brains. The results also suggest that brain function in Neanderthals may be more influenced by chromosomal errors than that of modern humans,” says Welland Huttner, who co-led the study. Svante Pääbo, who was also co-author of the study, adds that “future studies are needed to verify whether the low error rate affects modern human traits related to brain function.”
Scientists discover a new feature that distinguishes modern humans from Neanderthals
Felipe Mora-Bermúdez et al, Longer telophases and fewer segregation errors in chromosomes in modern humans than in Neanderthal brain development, science progress (2022). DOI: 10.1126 / sciadv.abn7702. www.science.org/doi/10.1126/sciadv.abn7702
Presented by the Max Planck Society
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