Asynchronous nuclear cycles in multinucleated Plasmodium falciparum facilitate rapid proliferation

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 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.

Automated summary

This study shows that individual nuclei replicate their DNA at different times, despite sharing a common cytoplasm. Mathematical modeling suggests the existence of a limiting factor that slows down nuclear multiplication. Experimental data supports the prediction that temporally overlapping DNA replication events are slower than partially or non-overlapping events. These findings suggest the presence of evolutionary pressure that selects for asynchronous DNA replication to balance resources and rapid pathogen proliferation.