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

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Russell, Andrew J.C. | Sanderson, Theo | Bushell, Ellen | Talman, Arthur | Anar, Burcu | Girling, Gareth | Hunziker, Mirjam | Kent, Robyn | Martin, Julie, S. | Metcalf, Tom | Montandon, Ruddy | Pandey, Vikash | Pardo, Mercedes | Roberts, A. Brett | Sayers, Claire | Schwach, Frank | Choudhary, Jyoti | Rayner, Julian | Voet, Thierry | Modrzynska, Katarzyna | Waters, Andrew P | Lawniczak, Mara K.N. | Billker, Oliver

Edité par CCSD -

International audience. Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient 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 female 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.

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