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.