Published on Wed Aug 04 2021

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

Russell, A. J. C., Sanderson, T., Bushell, E., Talman, A. M., Anar, B., Girling, G., Hunziker, M., Kent, R. S., Metcalf, T., Montandon, R., Pandey, V., Roberts, A. B., Sayers, C., Schwach, F., Rayner, J. C., Voet, T., Modrzynska, K. K., Waters, A. P., Lawniczak, M. K. N., Billker, O.

Transmission of malaria parasites from vertebrate host to mosquito vector 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

7
36
152
Abstract

The transmission of malaria parasites from vertebrate host to mosquito vector 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 ten genes essential for the formation of either male or female sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of wild-type and mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain points towards unexpected conservation of molecular mechanisms of gametogenesis in animals and a distantly related eukaryotic parasite.