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Modern Human Metaphase Slowdown Implicated in Accurate Chromosome Segregation, Brain Development

A team from the Max Planck Institute of Molecular Cell Biology and Genetics and other centers in Germany and Japan presents evidence for an extended metaphase step during the mitotic cell division process in humans compared to Neanderthals — a delay suspected of dialing down chromosome segregation errors. For their study, appearing in Science Advances, the investigators focused on half a dozen modern human amino acid substitutions occurring in proteins with pronounced stem cell and developing neocortex expression. By introducing these modern human-specific substitutions into genetically modified mice, they showed that amino acid changes in the KIF18a and KNL1 proteins appear to draw out metaphase and dampen segregation errors, while the ancestral version of the proteins present prior to the human-Neanderthal split coincided with an abbreviated metaphase stage and more error-prone chromosome segregation. "These results imply that the fidelity of chromosome segregation during neocortex development improved in modern humans after their divergence from Neanderthals," the authors write.