@article {328949,
	title = {Longer metaphase and fewer chromosome segregation errors in modern human than Neanderthal brain development.},
	journal = {Sci Adv},
	volume = {8},
	year = {2022},
	month = {2022 Jul 29},
	pages = {eabn7702},
	abstract = {<p>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.</p>
},
	keywords = {Animals, Brain, Chromosome Segregation, Hominidae, Humans, Kinesins, Metaphase, Mice, Neanderthals},
	issn = {2375-2548},
	doi = {10.1126/sciadv.abn7702},
	author = {Mora-Berm{\'u}dez, Felipe and Kanis, Philipp and Macak, Dominik and Peters, Jula and Naumann, Ronald and Xing, Lei and Sarov, Mihail and Winkler, Sylke and Oegema, Christina Eugster and Haffner, Christiane and Wimberger, Pauline and Riesenberg, Stephan and Maricic, Tomislav and Huttner, Wieland B and P{\"a}{\"a}bo, Svante}
}
