Asynchronous nuclear cycles in multinucleated Plasmodium falciparum enable rapid proliferation

Klaus, S.; Binder, P.; Kim, J.; Machado, M.; Funaya, C.; Schaaf, V.; Klaschka, D.; Kudulyte, A.; Cyrklaff, M.; Laketa, V.; Hoefer, T.; Guizetti, J.; Becker, N.; Frischknecht, F.; Schwarz, U. S.; Ganter, M.

doi:10.1101/2021.04.15.440016

bioRxiv · 10.1101/2021.04.15.440016

Asynchronous nuclear cycles in multinucleated Plasmodium falciparum enable rapid proliferation

Klaus, S.·Binder, P.·Kim, J.·Machado, M.·Funaya, C.·Schaaf, V.·Klaschka, D.·Kudulyte, A.·Cyrklaff, M.·Laketa, V.·Hoefer, T.·Guizetti, J.·Becker, N.·Frischknecht, F.·Schwarz, U. S.·Ganter, M.

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Abstract

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.

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Klaus, S., Binder, P., Kim, J., Machado, M., Funaya, C., Schaaf, V., Klaschka, D., Kudulyte, A., Cyrklaff, M., Laketa, V., Hoefer, T., Guizetti, J., Becker, N., Frischknecht, F., Schwarz, U. S., Ganter, M.. 2021-04-15. Asynchronous nuclear cycles in multinucleated Plasmodium falciparum enable rapid proliferation. https://doi.org/10.1101/2021.04.15.440016

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