Regulators of male and female sexual development are critical for the transmission of a malaria parasite

Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage par-asites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and suffi-cient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify genes essential for the formation of either male or fe-male sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of ten mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in the determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain as well as the protein interactors of a female-determining zinc-finger protein indicate that germ-granule-like ribonucleoprotein complexes complement transcriptional processes in the regulation of both male and female development of a malaria parasite.

Automated summary

Malaria transmission to mosquitoes requires a developmental switch in parasites. The transcription factor AP2-G is essential for this switch. The determination of the parasite's sex and its subsequent differentiation are regulated by a cascade of gene functions. Germ-granule-like ribonucleoprotein complexes complement transcriptional processes in the regulation of both male and female development of the parasite.