Abstract

Sexual reproduction and meiotic sex are deeply rooted in the eukaryotic tree of life, but the mechanisms determining sex or mating types are extremely varied and only well characterised in a few model organisms. Sexual differentiation in malaria parasites is initiated when a subset of intraerythrocytic parasites becomes committed to a sexual fate. Sexually committed parasites then undergo a secondary differentiation to become either male or female gametocytes. Sex determination is epigenetic, with each haploid parasite capable of producing either a male or a female gametocyte in the human host. The timing of the sex determination cell fate decision is not fully elucidated. Using a combination of cell fate mapping and single-cell approaches, we describe the timing of the sex-determining decision in malaria parasites. We further identify a gene that is both essential and sufficient for sex determination and begin to unravel the mechanism underlying sex determination in Plasmodium falciparum. Finally, we identify a transcriptional switch that controls mutually exclusive states at this locus, which govern the sex-determining cell fate decision. We show that sex determination in genetically identical cells requires a robust regulatory architecture acting on high-level regulators of a cell’s sexual fate. We place our results within the broader context of sex determination in alveolates.