More chromosome errors in Neanderthal brain than human brains

[Synapsid]

"Since the ancestors of modern humans separated from those of Neanderthals, around 100 amino acid substitutions spread to essentially all modern humans. The biological significance of these changes is largely unknown. Here, we examine all six such amino acid substitutions in three proteins known to have key roles in kinetochore function and chromosome segregation and to be highly expressed in the stem cells of the developing neocortex. When we introduce these modern human-specific substitutions in mice, three substitutions in two of these proteins, KIF18a and KNL1, cause metaphase prolongation and fewer chromosome segregation errors in apical progenitors of the developing neocortex. Conversely, the ancestral substitutions cause shorter metaphase length and more chromosome segregation errors in human brain organoids, similar to what we find in chimpanzee organoids. These results imply that the fidelity of chromosome segregation during neocortex development improved in modern humans after their divergence from Neanderthals."

" It is noteworthy that the magnitude of the shortening of AP metaphases seen in the ancestralized organoids is close to that previously observed between modern human and chimpanzee organoids (18). It is therefore possible that the three amino acid substitutions in KIF18a and KNL1 are largely responsible for the difference in AP metaphase length between present-day humans and apes. Given that the three ancestral amino acids are shared between chimpanzees and archaic humans, this implies that most, if not all, of the lengthening of AP metaphase evolved in modern humans subsequent to the divergence from archaic humans around half a million years ago.

"This may have significant consequences. During the early stage of this development, APs undergo symmetric proliferative divisions that increase the AP pool size (3–7, 53). Any chromosome segregation error that occurs in an AP at this stage will therefore be amplified by the natural AP proliferation, resulting in more APs with aberrant chromosome numbers. When APs switch to asymmetric divisions at the onset of cortical neurogenesis (3–7, 53), chromosomal aberrations may be transmitted to their progeny, i.e., the basal progenitors, cortical neurons, and macroglial cells. Therefore, any radial unit derived from an AP with a chromosome segregation error, and hence the cortical column that contains this unit (1, 54), might be functionally affected. Very different rates of neuronal aneuploidy in the brain have been reported in the literature. However, we note that the lagging chromosome percentages seen here are consistent with the percentages of aneuploidy reported for the human brain in recent studies (55–57). Mis-segregation may also result in apoptosis and loss of progenitors and the radial units they would have generated. In either case, consequences for the functionality of the entire neocortex area harboring an affected radial unit may ensue, for example, for excitatory pyramidal neurons and their numerous connections and projections. In addition, lingering chromosome segregation defects may have a variety of pleiotropic effects because of perturbed nuclear organization, increased occurrence of micronuclei, and imbalances in gene expression (58, 59). These effects may tend to be more profound than the effects of somatic point mutations that may be involved, for example, in autism spectrum disorder (60). The present data imply that the probability of any such detrimental effects of chromosomal mis-segregation may be lower in modern humans than in Neanderthals, Denisovans, and apes. Further work is needed to address the importance of these effects for traits characteristic of modern humans."
https://www.science.org/doi/10.1126/sciadv.abn7702

[Synapsid]

Maybe this explains why Humans outcompeted Neanderthals.