RT Journal Article SR Electronic T1 Asynchronous nuclear cycles in multinucleated Plasmodium falciparum enable rapid proliferation JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.15.440016 DO 10.1101/2021.04.15.440016 A1 Severina Klaus A1 Patrick Binder A1 Juyeop Kim A1 Marta Machado A1 Charlotta Funaya A1 Violetta Schaaf A1 Darius Klaschka A1 Aiste Kudulyte A1 Marek Cyrklaff A1 Vibor Laketa A1 Thomas Höfer A1 Julien Guizetti A1 Nils B. Becker A1 Friedrich Frischknecht A1 Ulrich S. Schwarz A1 Markus Ganter YR 2021 UL http://biorxiv.org/content/early/2021/04/15/2021.04.15.440016.abstract AB Malaria-causing parasites proliferate within erythrocytes through schizogony, forming multinucleated stages before cellularization. Nuclear multiplication does not follow a strict geometric 2n progression and each proliferative cycle produces a heterogeneous number of progeny. Here, by tracking nuclei and DNA replication, we show that individual nuclei replicate their DNA at different times, despite residing in a shared cytoplasm. Extrapolating from experimental data using mathematical modeling, we demonstrate that a limiting factor must exist that slows down the nuclear multiplication rate. Indeed, our data show that temporally overlapping DNA replication events were significantly slower than partially or non-overlapping events. Our findings suggest an evolutionary pressure that selects for asynchronous DNA replication, balancing available resources with rapid pathogen proliferation.Competing Interest StatementThe authors have declared no competing interest.