Asynchronous nuclear cycles in multinucleated <i>Plasmodium falciparum</i> facilitate rapid proliferation
Severina Klaus, Patrick Binder, Juyeop Kim, Marta Machado, Charlotta Funaya, Violetta Schaaf, Darius Klaschka, Aiste Kudulyte, Marek Cyrklaff, Vibor Laketa, Thomas Höfer, Julien Guizetti, Nils B. Becker, Friedrich Frischknecht, Ulrich S. Schwarz, Markus Ganter
Abstract
Malaria-causing parasites proliferate within erythrocytes through schizogony, forming multinucleated stages before cellularization. Nuclear multiplication does not follow a strict geometric 2 n progression, and each proliferative cycle produces a variable 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 provide strong indication that a limiting factor exists, which slows down the nuclear multiplication rate. Consistent with this prediction, our data show that temporally overlapping DNA replication events were significantly slower than partially overlapping or nonoverlapping events. Our findings suggest the existence of evolutionary pressure that selects for asynchronous DNA replication, balancing available resources with rapid pathogen proliferation.