DNA replication dynamics during erythrocytic schizogony in the malaria parasites Plasmodium falciparum and Plasmodium knowlesi

Malaria parasites are unusual, early-diverging protozoans with non-canonical cell cycles.  They do not undergo binary fission, but divide primarily by schizogony.  This is a mode of replication involving asynchronous production of multiple nuclei within the same cytoplasm, culminating in a single mass cytokinesis event.  The rate and efficiency of parasite replication is fundamentally important to malarial disease, which tends to be severe in hosts with high parasite loads.  Here, we have studied for the first time the dynamics of schizogony in two human malaria parasite species, Plasmodium falciparum and Plasmodium knowlesi.  These differ in their cell-cycle length, the number of progeny produced and the genome composition, among other factors.  Comparing them could therefore yield new information about the parameters and limitations of schizogony.  We report that the dynamics of schizogony differ significantly between these two species, most strikingly in the gap phases between successive nuclear replications, which are longer in P. falciparum and shorter, but more heterogenous, in P. knowlesi.  In both species, gaps become longer as schizogony progresses, whereas each period of active replication grows shorter.  In both species there is also extreme variability between individual cells, with some schizonts producing many more nuclei than others, and some individual nuclei arresting their replication for many hours while adjacent nuclei continue to replicate.  The efficiency of schizogony is probably influenced by a complex set of factors in both the parasite and its host cell.