Eukaryotic Centromere Remodeling: Plasticity, Dynamics, and Holocentromere Formation

ABSTRACT Eukaryotic centromeres highlight the remarkable plasticity of eukaryotic chromosomes through their conserved functionality and sequence divergence. Holocentric chromosomes, where centromere activity is distributed along the entire chromosome length, offer a unique model for investigating the molecular mechanisms underlying adaptive evolution between centromeres and chromosomes. In this review, we summarise and speculate on the multiple changes and prerequisites potentially involved in the evolution of holocentromeres. The interplay between environmental factors, chromosomal rearrangements, and centromere plasticity drives the transition from regional to holocentric characteristics. The centromeric histone H3 (CenH3) protein mediates neocentromere formation by recognising non‐centromeric chromosomal regions with appropriate AT content, thereby facilitating chromosome restructuring in the transition from regional to holocentric chromosomes. Dynamic changes in repetitive sequences provide functional sites for centromere assembly, chromosomal recombination and repair and centromere spreading and maturation. Epigenetic modifications maintain functional coordination among multiple centromeric units by modulating chromatin states, CenH3 localisation, and kinetochore assembly. This review provides a comprehensive framework for understanding the evolutionary mechanisms of holocentromeres derived from monocentromere and offers insights into the design of artificial centromeres.