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Journal Article

Longer metaphase and fewer chromosome segregation errors in modern human than Neanderthal brain development

MPS-Authors
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Mora-Bermúdez,  Felipe       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Kanis,  Philipp       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Macak,  Dominik
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Riesenberg,  Stephan       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;
The Leipzig School of Human Origins (IMPRS), Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Maricic,  Tomislav       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Pääbo,  Svante       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Fulltext (public)

Mora_Bermudez_Longer_SciAdvan_2022.pdf
(Publisher version), 3MB

Supplementary Material (public)

Mora_Bermudez_Longer_SciAdvan_2022_Suppl.pdf
(Supplementary material), 7MB

Citation

Mora-Bermúdez, F., Kanis, P., Macak, D., Peters, J., Naumann, R., Xing, L., et al. (2022). Longer metaphase and fewer chromosome segregation errors in modern human than Neanderthal brain development. Science Advances, 8: eabn7702. doi:10.1126/sciadv.abn7702.


Cite as: https://hdl.handle.net/21.11116/0000-000A-CC32-8
Abstract
Since the ancestors of modern humans separated from those of Neanderthals, around 100 amino acid substitu-
tions 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.