Malaria parasites regulate the duration of the intra-erythrocytic cycle via serpentine receptor 10 and coordinate development with host daily rhythms

Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 hours suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilising rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 hour rhythms in transcription under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 hour transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 hours; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinate development with host daily rhythms.