Modern human brain stem cells make fewer mistakes in the distribution of their chromosomes to daughter cells
Neanderthals were modern humans' closest relatives. A comparison with them can therefore provide essential insights into the uniqueness of contemporary humans, for example in relation to brain development. The neocortex, the largest portion of the cerebral cortex, is unique to mammals and is critical to many cognitive abilities. Researchers from the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden and the Max Planck Institute for Evolutionary Anthropology in Leipzig have now discovered that neural stem cells - the cells that are the origin of nerve cells in the developing neocortex - Modern humans take more time to prepare their chromosomes for cell division than Neanderthals. This leads to fewer errors in the distribution of chromosomes to daughter cells in modern humans compared to Neanderthals or chimpanzees and could have implications for brain development and function.
After the ancestors of modern humans separated from those of the 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 these changes spread to almost all modern humans. The biological significance of these changes is largely unknown. Six of these amino acid changes occurred in three proteins that play key roles in the distribution of the chromosomes, the carriers of genetic information, to the two daughter cells during cell division.
To study the impact of these six changes on 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 with these changes they could be a model for the development of the modern human brain. Felipe Mora-Bermúdez, the first author of the study, describes the research results: "We found that three amino acid changes in modern humans in two of these three proteins, namely in KIF18a and KNL1, cause a longer metaphase, a phase in which the Prepare chromosomes for cell division. This results in fewer errors in the distribution of chromosomes to neural stem cell daughter cells, just like in modern humans.”
To test whether the Neanderthal amino acids would have the opposite effect, the researchers converted the three modern-human amino acids back to the Neanderthal state, into so-called human brain organoids - miniature brain-like structures made from human stem cells in cell culture dishes in the laboratory can grow and which mimic early human brain development. "In this case, the metaphase was shortened and we found more errors in the chromosome distribution." According to Mora-Bermúdez, this shows that these three amino acid changes in the proteins KIF18a and KNL1 are responsible for the fact that modern humans have fewer chromosome distribution errors than Neanderthals and chimpanzees. He adds that errors in the number of chromosomes are usually unfavorable for the cells, which is evident in diseases such as trisomies and cancer.
"Our study suggests that some aspects of modern human brain development and function are independent of brain size, since Neanderthals and modern humans have similarly sized brains. The results also suggest that the brain function of Neanderthals was more strongly influenced 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 lower error rate affects traits of modern humans that are related to brain function."
Source: Press release Max Planck Society from February 29.07.2022, XNUMX