Abstract Cell proliferation involves duplication of all cell constituents and their more-or-less equal segregation to daughter cells. It seems probable that the performance of primitive cell-like structures would have been dogged by poor duplication and segregation fidelity, and by parasitism. This favoured evolution of the genome and with it the distinction between ‘genomic.’ components like chromosomes whose synthesis is periodic and most other ‘functional’ components whose synthesis is continuous. Eukaryotic cells evolved from bacterial ancestors whose fused genome was replicated from a single origin and whose means of segregating sister chromatids depended on fixing their identity at replication. Evolution of an endo- or cytoskeleton, initially as means of consuming other bacteria, eventually enabled evolution of the mitotic spindle and a new means of segregating sister chromatids whose replication could be initiated from multiple origins. In this primitive eukaryotic cell, S and M phases might have been triggered by activation of a single cyclin-dependent kinase whose destruction along with that of other proteins would have triggered anaphase. Mitotic non-disjunction would have greatly facilitated genomic expansion, now possible due to multiple origins, and thereby accelerated the tempo of evolution when permitted by environmental conditions.