Power-law scaling of mitotic spindles with genome sizes across eukaryotes is driven by chromosome crowding

Abstract

Abstract Genome size varies more than 10,000-fold across eukaryotes, yet how the mitotic spindle adapts to this range remains unknown. Here we show that metaphase plate width scales with genome size following a power law with an exponent of ~1/3 across eukaryotes. Comparative analysis and a physical model reveal that this scaling arises from the linear relationship between total chromosome volume and genome size, with chromosome number playing a secondary role. The same scaling holds across ploidy levels in cell lines, patient-derived cancer organoids and meiotic systems. Physical model and acute spindle compression demonstrate that chromosome crowding generates interchromosome pushing forces that set metaphase plate width. By contrast, spindle length is regulated by microtubule dynamics, cytoplasmic forces and cell size, indicating that spindle dimensions are independently controlled. The revealed scaling law provides a robust mechanism for accommodating large genomic variation and offers insight into the evolution of open mitosis and mitotic cell rounding, as well as polyploidy tolerance in tumours and during speciation.