During mitosis, centromeres connect chromosomes to spindle microtubules via kinetochores. Although most centromeres are monocentric, some metazoans have holocentric chromosomes with larger, diffuse kinetochores that interact with microtubules along the entire chromosome length. The kinesin motor protein CENP-E drives accurate chromosome segregation in many species, but its role in organisms with holocentric chromosomes remains unclear. Previously, Helder Maiato and colleagues showed that Indian muntjac deer chromosomes with larger kinetochores rely less on CENP-E and preferentially interact with spindle microtubules. Here (Almeida et al., 2024), the same research group investigate the relationship between kinetochore size and CENP-E dependence across species, comparing monocentric and holocentric chromosomes. Phylogenetic profiling reveals that CENP-E is often absent in taxa with holocentric chromosomes. Functional experiments demonstrate that expressing human CENP-E in Caenorhabditis elegans (which has holocentric chromosomes lacking CENP-E) partially rescues chromosome alignment defects induced by knockdown of the non-kinetochore kinesin KLP-19, suggesting that holocentric species have evolved compensatory alignment mechanisms. In support of this, inactivation of CENP-E in Pristionchus pacificus (which has holocentric chromosomes with CENP-E) has no impact on mitosis. This study highlights an inverse relationship between kinetochore size and CENP-E dependence, providing new insights into the evolution of kinetochore function across metazoans.
